VOLUME 4

AGENDA FOR RESEARCH

ON WOMEN’S HEALTH

FOR THE 21ST CENTURY

A Report of the Task Force on the

NIH Women’s Health Research Agenda 

for the 21st Century

INFLUENCES OF SEX AND

GENDER ON HEALTH

Scientific Meeting and Public Hearing

Philadelphia, Pennsylvania

September 1996

NATIONAL INSTITUTES 

OF HEALTH

Office of the Director

AGENDA FOR RESEARCH

ON WOMEN’S HEALTH

FOR THE 21ST CENTURY

A Report of the Task Force on the

NIH Women’s Health Research Agenda 

for the 21st Century

NATIONAL INSTITUTES 

OF HEALTH

Office of the Director

Office of Research 

on Women’s Health

VOLUME 4

Hosted by:

University of Pennsylvania School of Medicine

and

Allegheny University of the Health Sciences, 

MCP ◆Hahnemann School of Medicine

INFLUENCES OF SEX AND

GENDER ON HEALTH

Scientific Meeting and Public Hearing

Philadelphia, Pennsylvania

September 1996
U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health. Agenda

for Research on Women’s Health for the 21st Century. A Report of the Task Force on the NIH Women’s Health

Research Agenda for the 21st Century, Volume 4. Influences of Sex and Gender on Health. Bethesda, MD. 

NIH Publication No. 99-4388, 1999.
VOLUME 4

PREFACE

I

n September 1991, the Office of Research on Women’s Health (ORWH) of the National Institutes of 

Health (NIH) convened a meeting in Hunt Valley, Maryland, to assess the state of the science and to 

develop an agenda to guide women’s health research in the coming decade. The report generated by that 

meeting, National Institutes of Health: Opportunities for Research on Women’s Health, set forth the research 

recommendations developed by working groups focused on the major divisions of a woman’s life span and 

on scientific issues, diseases, and conditions that affect women’s health. That report has served as the broad 

blueprint for women’s health research at the National Institutes of Health. 

Now, several years later, science has continued to expand the parameters of knowledge, generating 

additional questions and pursuits. New public health issues and challenges emerging in the field of women’s 

health have demonstrated a need to re-examine and update the national agenda for women’s health research. 

To advance this concept, ORWH began a process to identify continuing or emerging gaps in knowledge and 

to provide research-based strategies that will result in improved health status for all women. This process 

included holding a series of public hearings and scientific workshops. 

The first regional conference was hosted by the University of Pennsylvania School of Medicine and 

Allegheny University of the Health Sciences in Philadelphia in September 1996. It focused on sex and gender

issues and their impact on research in women’s health; gaps in knowledge about women’s health; and successful

models for the recruitment, retention, re-entry, and advancement of women in biomedical careers. The second

regional meeting — hosted by Tulane University Medical Center, Xavier University of Louisiana, and Meharry 

Medical College — was held in New Orleans in June 1997. The New Orleans meeting focused on sex and gender

perspectives for women’s health research. The third in the series was held in Santa Fe, New Mexico, in July 1997, 

and was hosted by University of New Mexico School of Medicine and the University of Iowa College of Pharmacy. The Santa Fe meeting focused on differences among populations of women, factors that contribute to differences in their health status and health outcomes, and career issues for special populations of women. The final,

national meeting, convened in Bethesda, Maryland, in November 1997, and subtitled, Putting It All Together: 

The Agenda for Research on Women’s Health for the 21st Century, reviewed the deliberations and recommendations from the three regional public hearings and scientific workshops and developed the recommendations 

iii
iv

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

and priorities for updating the women’s health research agenda. All the meetings included an opportunity for 

public testimony as well as formal scientific sessions. Practitioners interested in women’s health; representatives

from scientific, professional, and women’s health organizations; and women’s health advocates have participated 

in the process and continue to provide guidance and expertise to ORWH.

The information presented in this volume represents the outcome of the Philadelphia regional meeting — 

the scientific workshops and the public testimony by individuals representing themselves or organizations with 

an interest in biomedical and behavioral research on women’s health, within the mandate of the National 

Institutes of Health. 

Additional volumes in this series consist of scientific workshop reports, presentations by distinguished 

scientists, and public testimony presented at the regional meetings in New Orleans and Santa Fe and at the 

national meeting in Bethesda. 
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iii

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vii

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

Working Group Reports

Cardiovascular Disease/Vascular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

Suzanne Oparil, M.D.; David Robinson, Ph.D.; Margaret E. Pickeral

Neuroscience, Behavior, and the Health of Women Across the Life Span . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

Raquel E. Gur, M.D., Ph.D.; Constance W. Atwell, Ph.D.; Mary Chunko

Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

Susana Serrate-Sztein, M.D.; Betty Diamond, M.D.; Donna M. Murasko, Ph.D.; Wanda Avila

Infectious Diseases and Emerging Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37

Sharilyn K. Stanley, M.D.; Howard Minkoff, M.D.; Donna R. Savage

Mental and Addictive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47

Delores L. Parron, Ph.D.; Elizabeth Young, M.D. 

Reproductive Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61

Donna Vogel, M.D., Ph.D.; Eugene Washington, M.D., M.P.H., M.Sc.; Michelle Berlin, M.D., M.P.H.; Nora Jacobsen

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71

Edward Trimble, M.D., M.P.H.; Karen Antman, M.D.; Rea Kerr Howarth

Research Designs: Multidisciplinary Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .81

Patricia Grady, Ph.D., R.N.; Brian Strom, M.D., M.P.H.; Susan Farer

Racial, Ethnic, and Cultural Diversity in Clinical Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .87

Virginia Cain, Ph.D.; Helen Rodriguez-Trias, M.D.; Wanda Avila

Research Designs: Gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97

George W. Counts, M.D.; Otis Brawley, M.D.; Rosalie Sagraves, Pharm.D.; Carollyne Hutter

Health Impact and Health Outcomes: Advances in Biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105

Judy Norsigian; Maria Freire, Ph.D.; Debra Powell

Preventive Interventions: Addressing Gender Differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111

Jane Pearson, Ph.D.; Marilyn Gaston, M.D.; Phyllis Greenberger, M.S.W.; Mary E. Cadette

Women in Biomedical Careers: Issues of Importance to Young Investigators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117

Eleanor Shore, M.D., M.P.H.; Anne Sassaman, Ph.D.; Rosanne Singer

Public Testimony

Introduction to the Public Testimony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127

Testimonies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129

Workshop Agenda and Participant Roster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .191

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .207

C O NTENTS

VOLUME 4

vii

VOLUME 4

The Office of Research on Women’s Health wishes to acknowledge the contributions of the following

individuals in planning this regional public hearing and scientific workshop held in Philadelphia, 

and for their assistance in bringing this meeting to fruition.

Michelle Berlin, M.D., M.P.H. 

University of Pennsylvania School of Medicine

Glenda Donoghue, M.D. 

Allegheny University of the Health Sciences

Bonita Falkner, M.D. 

Regional Cochair

Allegheny University of the Health Sciences

Rosa Fantasia, R.N., M.B.A. 

Allegheny University of the Health Sciences

Jeanne Ann Grisso, M.D., M.Sc. 

Regional Cochair

University of Pennsylvania School of Medicine

Jean Hamilton, M.D. 

Allegheny University of the Health Sciences and 

University of Pennsylvania School of Medicine

Sandra Levinson, M.D. 

Allegheny University of the Health Sciences

Donna Murasco, Ph.D. 

Allegheny University of the Health Sciences

Joyce Norden, Ph.D. 

University of Pennsylvania School of Medicine

ACKNOWLEDGMENTS

ix

VOLUME 4

COCHAIRS

Donna Dean, Ph.D.

Chief, Biological and Physiological Systems 

Division of Research Grants

National Institutes of Health

Bethesda, Maryland

Marianne Legato, M.D.

Associate Professor of Clinical Medicine 

Columbia University College of Physicians 

and Surgeons

New York, New York

TASK FORCE MEMBERS

Karen Antman, M.D.

Professor of Medicine and Pharmacology

Columbia University

Chief, Division of Medical Oncology

Columbia Presbyterian Comprehensive Cancer Center

New York, New York

Mary J. Berg, Pharm.D.

Professor

Division of Clinical and Administrative Pharmacy

University of Iowa

Iowa City, Iowa

Stephanie Bird, Ph.D.

Special Assistant to the Provost

Massachusetts Institute of Technology

Cambridge, Massachusetts

George Bryan, M.D.

Dean Emeritus, School of Medicine

University of Texas Medical Branch

Galveston, Texas

Leah Dickstein, M.D.

Professor and Associate Chair

Department of Psychiatry 

University of Louisville School of Medicine

Louisville, Kentucky

Mary Dufour, M.D., M.P.H.

Deputy Director

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Bethesda, Maryland

Carola Eisenberg, M.D.

Lecturer in Psychiatry 

Dean, Student Affairs (Retired)

Harvard Medical School

Boston, Massachusetts

John Estrada, M.D.

Assistant Professor of Pediatrics

Meharry Medical College

Nashville, Tennessee

Bonita Falkner, M.D.

Professor of Medicine and Pediatrics

Institute for Women’s Health

Allegheny University of Health Sciences

Philadelphia, Pennsylvania

Sheryle Gallant, Ph.D.

Associate Professor of Psychology

Department of Psychology

University of Kansas

Lawrence, Kansas

John Greene, D.M.D., M.P.H.

Professor and Dean Emeritus

School of Dentistry

University of California at San Francisco

San Rafael, California

Jeane Ann Grisso, M.D., M.Sc.

Associate Professor of Medicine

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania

Hazel Harper, D.D.S.

President, National Dental Association

Washington, District of Columbia

TASK FORCE ON THE NIH WOMEN’S HEALTH RESEARCH

AGENDA FOR THE 21ST CENTURY

OFFICE OF RESEARCH ON WOMEN’S HEALTH, NATIONAL INSTITUTES OF HEALTH
x

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Joseph Hurd Jr., M.D.

Chairman, Department of Gynecology

Lahey Hitchcock Clinic Medical Center

Burlington, Massachusetts

M. Margaret Kemeny, M.D., F.A.C.S.

Chief of Surgical Oncology

North Shore University Hospital

Manhasset, New York

Judith LaRosa, Ph.D., R.N., F.A.A.N. 

Professor and Chair

Department of Community Health Sciences

Tulane University Medical Center

School of Public Health and Tropical Medicine

New Orleans, Louisiana

Angela Barron McBride, Ph.D., R.N., F.A.A.N.

Distinguished Professor and Dean

Indiana University School of Nursing

Indianapolis, Indiana

Sherry Mills, M.D., M.P.H.

Acting Chief, Cancer Control Research Branch 

National Cancer Institute

National Institutes of Health

Bethesda, Maryland

Donnica Moore, M.D.

Associate Director

Sandoz Pharmaceuticals Medical Education Center

Sapphire Women’s Health Group

Nashamic Station, New Jersey

Judy Norsigian

Co-Director

Boston Women’s Health Book Collective 

Boston, Massachusetts

Jane Pearson, Ph.D.

National Institute of Mental Health

National Institutes of Health

Bethesda, Maryland

David Robinson, Ph.D.

Program Director

National Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland

Helen Rodriguez-Trias, M.D.

Co-Director, Pacific Institute for Women’s Health

Western Consortium for Public Health

Los Angeles, California

Rosalie Sagraves, Pharm.D.

Dean, College of Pharmacy

University of Illinois at Chicago

Chicago, Illinois

Gloria Sarto, M.D., Ph.D.

Professor 

University of New Mexico School of Medicine

Albuquerque, New Mexico

Anne Sassaman, Ph.D.

Director, Division of Extramural Research and Training

National Institute of Environmental Health Sciences

National Institutes of Health

Bethesda, Maryland

Ora Lee Strickland, Ph.D.

Independence Professor

Nell Hodgson Woodruff School of Nursing

Emory University

Atlanta, Georgia

Ramona Tascoe, M.D., M.H.S.A.

Chair, Council on the Concerns of Women Physicians

Kaiser/National Medical Association

Oakland, California

Constance Weinstein, Ph.D.

National Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland

Darlene Yee, Ed, C.H.E.S.

Professor and Director, Gerontology

College of Health and Human Services

San Francisco State University

San Francisco, California

Members-at-Large

Coordinating Committee on Research on Women’s 

Health Members

Advisory Committee on Research on Women’s

Health Members
xi

VOLUME 4

Roster, 1996

CHAIRPERSON

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland

EXECUTIVE SECRETARY

Anne R. Bavier, M.N., F.A.A.N.

Deputy Director

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland

COMMITTEE MEMBERS

Dyanne D. Affonso, Ph.D., F.A.A.N.

Dean and Professor

Nell Hodgson Woodruff School of Nursing

Emory University

Atlanta, Georgia

Kathy S. Albain, M.D.

Associate Professor of Medicine

Division of Hematology and Oncology

Loyola University Medical Center

Chair, Southwest Oncology Group Committee 

on Women’s Health 

Maywood, Illinois 

Carol A. Aschenbrener, M.D.

Professor of Pathology

University of Nebraska Medical Center

Omaha, Nebraska

Byllye Y. Avery, M.Ed.

Founder

National Black Women’s Health Project

Swarthmore, Pennsylvania 

Mary J. Berg, Pharm.D.

Professor

Division of Clinical and Administrative Pharmacy

College of Pharmacy

University of Iowa

Iowa City, Iowa 

Edward N. Brandt, Jr., M.D., Ph.D.

Professor and Director

Center for Health Policy Research and Development

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 

David M. Brown, M.D.

Professor of Pediatrics, Laboratory Medicine, 

and Pathology

Head, Division of Pediatric Endocrinology

School of Medicine

University of Minnesota

Minneapolis, Minnesota

Linda Burhansstipanov, M.S.P.H., Dr.P.H.

Director

Native American Cancer Center

AMC Cancer Research Center

Denver, Colorado 

John J. Estrada, M.D.

Assistant Professor of Pediatrics

Department of Pediatrics

Meharry Medical College

Nashville, Tennessee 

Sheryle J. Gallant, Ph.D.

Associate Professor of Psychology

Department of Psychology

University of Kansas

Lawrence, Kansas 

W. Lou Glasse, M.S.W.

President Emerita

Older Women’s League

Vassar College

Poughkeepsie, New York

ADVISORY COMMITTEE ON RESEARCH ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH 
xii

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Irma E. Goertzen

President and Chief Executive Officer

Magee-Women’s Hospital

Pittsburgh, Pennsylvania 

John C. Greene, D.M.D., M.P.H.

Professor and Dean Emeritus

School of Dentistry

University of California at San Francisco

San Rafael, California

Marianne J. Legato, M.D., F.A.C.P.

Internist and Specialist in Women’s Health

Department of Medicine

Columbia University

New York, New York 

Amelie G. Ramirez, Dr.P.H.

Associate Professor

Department of Family Practice

Director, South Texas Health Research Center

University of Texas Health Science Center 

at San Antonio

San Antonio, Texas

Gloria E. Sarto, M.D., Ph.D.

Professor and Chair

Department of Obstetrics and Gynecology

School of Medicine

University of New Mexico

Albuquerque, New Mexico

Marjorie M. Shultz, J.D., M.A.T.

Professor of Law

Boalt Hall School of Law

University of California at Berkeley

Berkeley, California 

Nancy Sabin Wexler, Ph.D.

Higgins Professor of Neuropsychology

College of Physicians and Surgeons of 

Columbia University

New York, New York
xiii

VOLUME 4

COORDINATING COMMITTEE ON RESEARCH ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

Roster, September 1996

Norman Anderson, Ph.D.

Director

Office of Behavioral and Social Sciences Research

Office of the Director 

Inese Beitins

Director, General Clinical Research Centers Program

National Center for Research Resources

Tina Blakeslee

Legislative Liaison and Analysis Branch

Office of the Director

Diana Blithe

Intramural Scientist

National Institute of Child Health and 

Human Development

Kristina Borror

Scientist

Office of Science Policy

Office of the Director

Joy Boyer

Program Analyst

National Center for Human Genome Research

Stephanie Bursenos

Assistant Director for Program Coordination

John E. Fogarty International Center

Virginia Cain, Ph.D.

Special Assistant to the Director

Office of Behavioral and Social Sciences Research

Office of the Director 

Paul Coates, Ph.D. 

Director, Diabetes Program Branch

National Institute of Diabetes and Digestive and 

Kidney Diseases

Lois Ann Colaianni, Ph.D.

Associate Director, Library Operations

National Library of Medicine

Alison E. Cole, Ph.D. 

Program Administrator

PBC Program

National Institute of General Medical Sciences

Terri Damstra

Associate Director for International Programs and 

Program Coordination

National Institute of Environmental Health Sciences

Katherine Davenny

Clinical Medicine Branch

National Institute on Drug Abuse

Donna Dean, Ph.D.

Chief

Biological and Physiological Systems

Division of Research Grants

Amy Donahue, Ph.D.

Acting Chief

Hearing and Balance/Vestibular Sciences Branch

National Institute on Deafness and Other 

Communication Disorders

Mary Dufour, M.D., M.P.H.

Deputy Director

National Institute on Alcohol Abuse and Alcoholism

Robert Eisinger, Ph.D.

Senior Program Analyst

Office of AIDS Research

Office of the Director

Shirley Everest

Acting Federal Women’s Program Manager

Office of Equal Opportunity

Office of the Director

Loretta Finnegan, M.D.

Director

Women’s Health Initiative

Office of the Director
xiv

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Julia Freeman, Ph.D.

Director, Centers Program

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

Harriet Gordon

Medical Officer

National Center for Research Resources

Eleanor Hanna, Ph.D.

Special Expert

Division of Biometry and Epidemiology

National Institute on Alcohol Abuse and Alcoholism

J. Taylor Harden, Ph.D. 

Health Promotion and Disease Prevention Branch

National Institute of Nursing Research

Jean Harris

Nursing Specialist for Quality Assurance

Warren Grant Magnuson Clinical Center

Barbara Harrison 

Special Projects Officer

Division of Nutrition Coordination 

National Institute of Diabetes and Digestive and 

Kidney Diseases

Janyce Hedetniemi

Director

Office of Community Liaison

Office of the Director 

Sharon Hrynkow, Ph.D.

Office of International Science Policy and Analysis

John E. Fogarty International Center

Carole Hudgings, Ph.D., F.A.A.N.

Program Officer

Office of Alternative Medicine

Office of the Director

Chyren Hunter, Ph.D.

Health Science Administrator

Division of Human Communication

National Institute on Deafness and Other 

Communication Disorders

Josefa Ippolito-Shepherd

Public Health Analyst

John E. Fogarty International Center

Laura James

Nurse Scientist Administrator

National Institute of Nursing Research

Walter Jones

Deputy Director of Management and Operations

Warren Grant Magnuson Clinical Center

Elke Jordan, Ph.D.

Deputy Director

National Center for Human Genome Research 

Bonnie Kalberer

Special Assistant

Office of Science Policy

Office of the Director

Dushanka Kleinman, D.D.S.

Deputy Director

National Institute of Dental Research

Natalie Kurinij

Health Scientist Administrator

National Eye Institute

Ellen S. Liberman, Ph.D.

Director

Lens, Cataract, and Glaucoma Programs

National Eye Institute

Barbara Liu

Director of Scientific and Legislative Programs

National Heart, Lung, and Blood Institute 

Angela Magliozzi

Women’s Health Program Coordinator

National Institute of Allergy and Infectious Diseases

Bernadette Marriott, Ph.D.

Director, Office of Dietary Supplements

Office of the Director

Dorothy McKelvin

Contract Specialist

Office of Equal Opportunity

Office of the Director

Anne Middleswarth

Program Analyst

National Cancer Institute
xv

VOLUME 4

Mary Miers

Chief, Legislation and Analysis Branch

National Institute of Neurological Disorders and Stroke

Sheila Newton

Director

Office of Program Planning and Evaluation

National Institute of Environmental Health Sciences

Cherie Nichols

Chief, Planning and Evaluation Branch

National Cancer Institute

Barbara Packard, M.D.

Associate Director for Scientific Program Operations

National Heart, Lung, and Blood Institute

Delores Parron, Ph.D.

Associate Director for Special Populations

National Institute of Mental Health

Estella Parrott, M.D. 

Coordinator of Research Programs

National Institute of Allergy and Infectious Diseases

Jane Peterson, Ph.D. 

Chief, Mammalian Genomics Branch

National Center for Human Genome Research

Sherman Ragland, Ph.D.

Deputy Director, Office for Special Populations

National Institute of Mental Health

Mary Ann Robinson

Senior Scientist

National Institute of Allergy and Infectious Diseases

David Rodbard

Director

Division of Computer Research and Technology

Adele Roman, M.S.N.

Deputy Women’s Health Coordinator

National Institute on Drug Abuse

Angela Ruffin, Ph.D.

Outreach Librarian

National Library of Medicine

John Ruffin, Ph.D.

Director, Office of Research on Minority Health

Office of the Director

Anne Sassaman, Ph.D.

Director, Division of Extramural Research and Training

National Institute of Environmental Health Sciences 

Belinda Seto, Ph.D.

Senior Advisor 

Office of Extramural Research

Office of the Director

Louis Sibal, Ph.D.

Director, Office of Laboratory Research

Office of the Director 

Sandra Smith-Gil

Senior Scientist

National Cancer Institute

Susan Stark

Writer-Editor

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

Mary Stephens-Frazier

Health Scientist Administrator

National Institute for Nursing Research

Patricia Straat, Ph.D.

Deputy Chief for Referral

Center for Scientific Review

Susan Swedo, M.D.

Medical officer

National Institute of Mental Health

Anne Thomas

Director

Office of Communications

Office of the Director 

Elizabeth Thomson

Assistant Director

Clinical Genetics Branch

National Human Genome Research Institute

Patricia Turner

Program Analyst 

National Institute of Neurological Disorders and Stroke

Donna Vogel, M.D., Ph.D.

Medical Officer, Reproductive Sciences Branch

National Institute of Child Health and 

Human Development 
xvi

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Carol E. Vreim, Ph.D.

Deputy Director, Division of Lung Diseases

National Heart, Lung, and Blood Institute

CoraLee Wetherington, Ph.D.

Women’s Health Coordinator

National Institute on Drug Abuse

Judith Whalen

Chief, Office of Science Policy and Analysis

National Institute of Child Health and 

Human Development 

Susan Wise

Program Analyst

Planning and Legislation Section

National Institute of Dental Research

Rosemary Yancik

Assistant Director

Liaison and Applied Research

National Institute on Aging

Chris Zimmerman

Program Analyst

National Institute of General Medical Sciences
COORDINATING COMMITTEE ON RESEARCH ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

xvii

VOLUME 4

Research Subcommittee Roster, September 1996

COCHAIRS

Donna Dean, Ph.D. 

Chief, Biological and Physiological Systems

Division of Research Grants

David Robinson, Ph.D. 

National Heart, Lung, and Blood Institute

ORWH

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

Joyce Rudick

Senior Program Analyst

Office of Research on Women’s Health

COMMITTEE MEMBERS

Mary Blehar, Ph.D.

National Institute of Mental Health

Pat Bryant, Ph.D.

National Institute of Dental Research

Paul Coates, Ph.D.

National Institute of Diabetes and Digestive 

and Kidney Diseases

Elaine Collier, Ph.D.

National Institute of Allergy and Infectious Diseases

Pamela Marino, Ph.D.

National Institute of General Medical Sciences

Sherry Mills, M.D.

National Cancer Institute

Ted Trimble, M.D.

National Cancer Institute

Donna Vogel, M.D., Ph.D.

National Institute of Child Health and 

Human Development 

Anita Weinblatt, Ph.D.

Division of Research Grants

xix

VOLUME 4

COORDINATING COMMITTEE ON RESEARCH ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

Career Development Subcommittee Roster, 

September 1996

COCHAIRS

Anne Sassaman, Ph.D.

National Institute of Environmental Health Sciences

Julia Freeman, Ph.D.

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases 

ORWH

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

Joyce Rudick

Senior Program Analyst

Office of Research on Women’s Health

COMMITTEE MEMBERS

Jim Alexander, Ph.D.

Office of Education

Office of the Director

Ed Donohue

National Institute of Neurological Diseases and Stroke

Miriam Kelty, Ph.D.

National Institute on Aging

Walter Schaffer, Ph.D.

Office of Extramural Research

Gloria Seelman

Office of Science Education

Office of the Director

xxi

VOLUME 4

PHILADELPHIA, PENNSYLVANIA

SEPTEMBER 25-27, 1996

WORKING GROUP COCHAIRS

CANCER

Edward Trimble, M.D., M.P.H.

Head, Surgery Section

Cancer Therapy Evaluation Program

Division of Cancer Treatment, Diagnosis, and Centers

National Cancer Institute

National Institutes of Health

Bethesda, Maryland

Karen Antman, M.D.

Professor of Medicine 

Chief, Division Medical Oncology

Columbia University

New York, New York

CARDIOVASCULAR DISEASE/VASCULAR BIOLOGY

David Robinson, Ph.D.

Program Director 

National Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland

Suzanne Oparil, M.D.

Director

Vascular Biology and Hypertension Program

University of Alabama at Birmingham

Birmingham, Alabama

HEALTH IMPACT AND HEALTH OUTCOMES: 

ADVANCES IN BIOTECHNOLOGY

Judy Norsigian

Co-Director

Boston Women’s Health Book Collective

Boston, Massachusetts

Maria Freire, Ph.D.

Director, Office of Technology Transfer

National Institutes of Health

Bethesda, Maryland

IMMUNOLOGY

Susana Serrate-Sztein, M.D.

Director, Arthritis Program

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

National Institutes of Health

Bethesda, Maryland

Betty Diamond, M.D.

Professor 

Departments of Microbiology and Immunology 

and Medicine

Albert Einstein College of Medicine

Bronx, New York

Donna M. Murasko, Ph.D.

Professor and Chair

Department of Microbiology and Immunology

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania

INFECTIOUS DISEASES AND EMERGING INFECTIONS

Sharilyn K. Stanley, M.D.

Special Assistant for Science Policy

Office of the Director

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland

Howard Minkoff, M.D.

SUNY Health Science Center at Brooklyn

Brooklyn, New York

MENTAL AND ADDICTIVE DISORDERS

Delores L. Parron, Ph.D.

Associate Director for Special Populations

National Institute of Mental Health

National Institutes of Health

Bethesda, Maryland

BEYOND HUNT VALLEY: 

RESEARCH ON WOMEN’S HEALTH FOR THE 21ST CENTURY
xxii

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Elizabeth Young, M.D.

Associate Professor of Psychiatry

Mental Health Research Institute

University of Michigan

Ann Arbor, Michigan 

NEUROSCIENCE, BEHAVIOR, AND THE HEALTH OF WOMEN

ACROSS THE LIFE SPAN

Raquel E. Gur, M.D., Ph.D.

Professor and Director of Neuropsychiatry 

University of Pennsylvania

Philadelphia, Pennsylvania

Constance W. Atwell, Ph.D.

Associate Director, Extramural Activities

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Bethesda, Maryland

PREVENTIVE INTERVENTIONS: ADDRESSING

GENDER DIFFERENCES

Jane Pearson, Ph.D.

Chief

Clinical and Developmental Psycho-Pathology Program

Mental Disorders of the Aging Research Branch

National Institute of Mental Health

National Institutes of Health

Bethesda, Maryland

Marilyn Gaston, M.D.

Assistant Surgeon General

Director, Bureau of Primary Health Care 

Health Resources and Services Administration

Rockville, Maryland

Phyllis Greenberger, M.S.W.

Executive Director

Society for the Advancement of Women’s 

Health Research

Washington, District of Columbia

RACIAL, ETHNIC, AND CULTURAL DIVERSITY IN

CLINICAL RESEARCH

Virginia Cain, Ph.D.

Special Assistant to the Director

Office of Behavioral and Social Science Research

Office of the Director

National Institutes of Health

Bethesda, Maryland

Helen Rodriguez-Trias, M.D.

Co-Director

Pacific Institute for Women’s Health

Western Consortium for Public Health

Los Angeles, California

REPRODUCTIVE HEALTH

Donna Vogel, M.D., Ph.D.

Associate Chief for Clinical Research Reproductive 

Sciences Branch

National Institute of Child Health and Human 

Development

National Institutes of Health

Bethesda, Maryland

Eugene Washington, M.D., M.P.H., M.Sc.

Professor and Chair

Department of Obstetrics and Gynecology

University of California at San Francisco

San Francisco, California

Michelle Berlin, M.D., M.P.H.

Assistant Professor of Obstetrics and Gynecology 

and Epidemiology

Center for Clinical Epidemiology and Biostatistics

University of Pennsylvania

Philadelphia, Pennsylvania

RESEARCH DESIGNS: GENDER

George W. Counts, M.D.

Director

Office of Research on Minority and Women’s Health

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland

Otis Brawley, M.D.

Director, Office of Special Populations

National Cancer Institute

National Institutes of Health

Bethesda, Maryland

Rosalie Sagraves, Pharm.D.

Dean and Professor

College of Pharmacy

University of Illinois at Chicago

Chicago, Illinois
xxiii

VOLUME 4

RESEARCH DESIGN: MULTIDISCIPLINARY PERSPECTIVES

Patricia Grady, Ph.D., R.N.

Director

National Institute of Nursing Research

National Institutes of Health

Bethesda, Maryland

Brian Strom, M.D., M.P.H.

Professor and Chair

Department of Biostatistics and Epidemiology

Director, Center for Clinical Epidemiology 

and Biostatistics

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania

WOMEN IN BIOMEDICAL CAREERS: ISSUES OF IMPORTANCE

TO YOUNG INVESTIGATORS

Eleanor Shore, M.D., M.P.H.

Dean, Faculty Affairs 

Harvard Medical School

Boston, Massachusetts

Anne Sassaman, Ph.D.

Director, Division of Extramural Research and Training

National Institute of Environmental Health Sciences

National Institutes of Health

Bethesda, Maryland

This workshop and scientific meeting, sponsored by the Office of Research on Women’s

Health (ORWH) of the National Institutes of

Health (NIH), elicited participants’ views concerning

NIH’s agenda for research on women’s health for the 

21st century.

From the excellent and informative public testimony presented at the public hearing and the recommendations received, ORWH re-examined NIH’s 

existing agenda for women’s health research. Drawing on participants’ wisdom and insight and availing

ourselves of scientific directives in a science-driven

agenda, we worked in concert with the members 

of ORWH’s Task Force on the NIH Women’s Health

Agenda for the 21st Century, the Advisory Committee on Research on Women’s Health, and the 

Coordinating Committee on Research on Women’s

Health to re-examine NIH’s priorities in women’s 

health research. The goal was to direct, or redirect,

NIH’s future endeavors in biomedical and behavioral

research, so that the knowledge that we gained in

recent years and the momentum that our collective

efforts generated would be used to preserve and

improve the health and well being of women.

I wish to acknowledge the wonderful, sincere, 

and dedicated contributions of Iris Schneider, of 

the National Cancer Institute, to women’s health

research at NIH. We miss her today, as we know she

would have been here to guide and inspire our efforts.

Iris was instrumental in the development of our Office

1

VOLUME 4

INTRODUCTION

and its programs across NIH. With her death just a 

few weeks ago, she left a great void in the women’s

health community; we mourn for her friendship, 

her tireless energy, her unrelenting commitment 

to women’s health research, and her boundless 

courage in the face of her own ovarian cancer. 

The major charge during this workshop was 

to help us determine future directions for women’s

health research and a myriad of related issues. There 

is no question that research is central to providing 

the scientific foundation for change and improvement 

in women’s health. There must be multidisciplinary

collaboration involving multiple partners who share

the responsibility to establish and disseminate new

information that results from increased and enhanced

research on women’s health. We must also collaborate in implementing and translating the findings of

research in health care delivery, and we must seek

innovative strategies for influencing the behavior 

and health practices, not only of the scientific and

medical communities, but also of individual women 

and their families.

We know that to bring about change in women’s

health research, there must be a coalition of effort that

includes the scientific and health care communities,

those involved in professional education, federal agencies, women’s health advocacy groups, and, most

importantly, women and their families and communities. History has demonstrated that when these

groups work in harmony with concerted effort, 

significant improvements can occur.

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

National Institutes of Health
As Assistant Secretary for Health, Dr. Brandt said that

he was “committed to seeing that this report results in

action that is beneficial to the women of America.” 3 This

report and commitment thus launched the federal 

initiatives to address women’s health.

HISTORY OF INCLUSION

POLICIES AT THE

NATIONAL INSTITUTES

OF HEALTH

The establishment and implementation of policies

for the inclusion of women and minorities in clinical

research funded by NIH has its origins in the women’s

health movement. Following the issuance of the report

of the PHS Task Force on Women’s Health Issues in

1985, NIH established a policy for the inclusion of

women in clinical research. 

This policy, which urged the inclusion of women,

was first published in the NIH Guide to Grants and 

Contracts in 1987. In a later version of the NIH Guide, 

a policy encouraging the inclusion of minorities in 

clinical studies was first published.

The Congressional Caucus for Women’s Issues, 

at the encouragement of the Society for the Advancement of Women’s Health Research, requested that 

the General Accounting Office (GAO) investigate 

the implementation by NIH of the guidelines for 

the inclusion of women. In 1990, this GAO report 

stated that the policy for the inclusion of women 

was implemented inconsistently across NIH.4

Just 3 months after the release of the GAO report,

in September 1990, the Office of Research on Women’s

Health (ORWH) was established at NIH. In fact, the

press release announcing the formation of this office

was dated Monday, September 10.

2

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

History also demonstrates that the focus on

women’s health and the women’s health movement are

not new. The Boston Women’s Health Book Collective

just celebrated the 25th anniversary of the legendary

tome, Our Bodies, Ourselves: A Book by and for Women,1

and the National Women’s Health Network and the

National Black Women’s Health Network, among many

others, are advocacy and action groups that have been

around for years — working in the “trenches,” so to

speak — to call attention to the need to focus our

attention on women’s health. In recent years, the Federal Government has recognized women’s health as a

priority requiring significant attention and resources.

Today, thanks to the efforts of many, we are beginning 

to make progress. 

THE PHS TASK FORCE

AND THE ESTABLISMENT 

OF ORWH

In 1983, the Assistant Secretary for Health, Dr.

Edward N. Brandt, established the Public Health Service (PHS) Task Force on Women’s Health Issues to

examine the role of the Department of Health and

Human Services in addressing women’s health. This

Task Force issued a number of recommendations on a

broad array of women’s health issues across the entire

life span of women in a report published in 1985. 

Among the recommendations of the Task Force

report was one which stated: 

Biomedical and behavioral research should be

expanded to ensure emphasis on conditions and

diseases unique to, or more prevalent in, women

in all age groups.2
3

VOLUME 4

ORWH was given a threefold mandate: 

• First, to strengthen, develop, and increase research

into diseases, disorders, and conditions that affect

women, determining gaps in knowledge about

such conditions and diseases, and then establish 

a research agenda for NIH for future directions 

in women’s health research.

• Second, to ensure that women are appropriately

represented in biomedical and biobehavioral

research studies, especially clinical trials, that 

are supported by NIH; and

• Third, to create direct initiatives to increase the

number of women in biomedical careers and 

to facilitate their advancement and promotion.

Since the establishment of ORWH, our responsibilities and major program efforts have increased 

and, in 1993, our office was legislatively mandated 

in the NIH Revitalization Act. 

ORWH has taken the leadership in implementing policies requiring the inclusion of women and

minorities in human subject research. Wanting to

ensure that the policies for inclusion were firmly 

implemented by NIH, Congress made what had 

previously been policy into Public Law, through 

a section in the National Institutes of Health Revitalization Act of 1993, entitled, “Women and 

Minorities as Subjects in Clinical Research.”5

The National Institutes of Health Revitalization 

Act of 1993 essentially put forth the existing NIH 

policies, but with four major differences:

• that NIH ensure that women and minorities 

and their subpopulations be included in all 

human subject research;

• that women and minorities and their subpopulations be included in Phase III clinical trials in

numbers adequate to allow for valid analyses 

of differences in intervention effect;

• that cost is not allowed as an acceptable 

reason for excluding these groups; and

• that NIH initiate programs and support for 

outreach efforts to recruit and retain women 

and minorities and their subpopulations as 

volunteers in clinical studies.

The guidelines for inclusion developed in response

to this law were published in the Federal Register 6 in

March 1994, and they have been fully implemented. 

ORWH has also convened two meetings of Institutional Review Board(s) chairs and representatives 

to determine potential remaining barriers to the 

implementation of this policy.

ORWH’s mandate on inclusion also calls for 

the development of a tracking system to monitor 

the inclusion of women and minorities in clinical 

trials. By working in collaboration with the Office 

of Extramural Research, ORWH has developed a 

tracking system, which is now in place. For the first 

time, we are now able to determine the numbers 

of women and minorities included in human subject research. As we collect additional data, we will 

determine how best to interpret these figures.

ORWH also funded the Institute of Medicine 

study Women and Health Research,7 which is an excellent report on the legal and ethical issues related 

to women, especially women of childbearing age, 

in human subject research. 

To address concerns about the inclusion of 

women in clinical trials, ORWH held a public hearing

and workshop in July 1993 on the recruitment and

retention of women. The report of that study8 is available to assist investigators who seek information to 

aid them in their efforts. 

In June 1992, ORWH had held a public hearing

and workshop on the recruitment, retention, advancement, and re-entry of women in biomedical careers.
4

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Using the report from this meeting,9 which identifies

barriers to women entering or advancing in scientific

careers, ORWH established a number of programs,

including our re-entry scientists program and other 

initiatives, to help develop the careers of women and

men scientists and to stimulate research on women’s

health issues. These programs include workshops 

on how to speak and write about science. 

Under the leadership of Joyce Rudick, Senior Program Analyst, and Dr. Anne Sassaman, Cochair of our

Coordinating Committee on Research on Women’s Health

Career Development Subcommittee, we have evaluated

the re-entry program and are now looking for ways to

expand this and other ORWH initiatives. Suggestions

received during the public hearing and recommendations from the working group on young investigators

were of great assistance to us in this endeavor. 

While much remains to be done to address the

many pressing issues in women’s health, it is all too 

easy to focus only on the gaps in knowledge that

remain, forgetting where we started and how far 

we have traveled. 

ORWH convened this meeting, “Beyond Hunt 

Valley: Research on Women’s Health for the 21st Century,” to look ahead, but also to pause for a moment 

to reflect on our progress to date. Since 1991, the

national agenda on women’s health research has 

been shaped by certain underlying principles that 

must continue to inform our directions for the 

future. The basis for our original agenda began 

with the report, National Institutes of Health: Opportunities for Research on Women’s Health (referred to 

hereafter as the Hunt Valley Report).10 This agenda 

was formulated from a public hearing and workshop

held in September 1991 in Hunt Valley, Maryland. 

In the agenda, the parameters of women’s health 

were expanded and redefined, and research has 

been redirected to provide better information on 

sex and gender differences between women and 

men in normative development, health, and disease.

The NIH agenda recognizes the full spectrum 

of research from clinical to basic, behavioral to epidemiological. We have also recognized the many 

gender issues that must be taken into account in

designing clinical research studies. The agenda 

emphasizes the need to proceed from an expanded 

concept of women’s health: one that crosses scientific disciplines and medical specialties to examine

women’s health across the life span and that focuses 

on outreach to populations of women and girls who

have been previously excluded from scientific investigation. Including minorities, women of low socioeconomic status and diverse geographic locations, 

and lesbians is an integral part of ORWH’s research

agenda. In all of our efforts to implement our research

agenda, we are pursuing active and beneficial partnerships with all NIH institutes, divisions, and centers.

The 1991 Hunt Valley meeting led to our current working research document. We believe that it 

is time to look “beyond Hunt Valley,” to update our 

priorities, and go beyond research to consider how 

best to implement the results of such research. We 

found the model of broad participation in this process through public hearings and workshops with 

representative and voluntary participation to be 

most effective, and we have thus turned again 

to this model. 

We asked working groups to:

• Identify scientific progress since the establishment of ORWH;

• Highlight successes in the advances of scientific

knowledge about women’s health and gender 

and sex information;

• Highlight programs that have advanced women’s

health research;

• Develop strategies for identifying continuing 

or emerging gaps in knowledge and how to 

address them;
5

VOLUME 4

• Generate recommendations for future research 

priorities and necessary consideration of the biomedical and behavioral research community;

• Provide pathways for networking and collaboration among researchers; and

• Consider effective implementation of research outcomes in public policy and health care of women,

with consideration of changing parameters (e.g.,

advances in biotechnology, managed care, etc.).

Participants were told to keep in mind that all 

of our programs and initiatives should be science 

driven. They were asked to consider how, where, 

and in what manner we can best ensure implementation of the results of our advances from research.

Their role was a significant and meaningful one. Our

updated agenda reaffirms NIH’s commitment to an 

integration of scientific disciplines and medical specialties with advocacy and forward-thinking optimism.

With the creation of new laws, policies, and 

programs, we have made tangible progress toward

improving women’s health, and we have gained a 

sure sense of our power to effect real change. With

your assistance, as we enter into the 21st century,

ORWH can build on that power and maximize its

efforts to improve the health of women and their 

families. That is ORWH’s and NIH’s vision for 

women’s health in the United States and beyond, 

which we are trusting to you to help us ensure for 

the future. No single individual or group can do the 

job alone. The challenge — and the responsibility 

— must be shared by all of us.

References

1 Boston Women’s Health Book Collective. Our Bodies, 

Ourselves: A Book by and for Women. New York: Simon 

and Schuster, 1971.

2 U.S. Public Health Service. Women’s Health: Report of 

the Public Health Service Task Force on Women’s Health 

Issues. Vol. 1, no. 1 (January-February, 1985): 1:76. 

3 Ibid.

4 Nadel, MV. National Institutes of Health: Problems in Implementing Policy on Women in Study Populations. Washington,

D.C.: U.S. General Accounting Office, June 1990.

5 National Institutes of Health Revitalization Act of 1993.

(Public Law 103-43), 107 Stat. 22, (codified at 42 USC:

Sec. 289.a-1), June 10, 1993.

6 NIH Guidelines on the Inclusion of Women and Minorities

as Subjects in Clinical Research; Notice. Federal Register,

March 28, 1994. DHHS/NIH/Part VIII, vol. 59, no. 59, 

pp. 14508-14513.

7 Mastroianni, A.C., R. Faden, and D. Federman (eds.).

Women and Health Research: Ethical and Legal Issues of

Including Women in Clinical Studies. Washington, D.C.:

National Academy Press, 1994.

8 U.S. Department of Health and Human Services, National

Institutes of Health, Recruitment and Retention of Women 

in Clinical Studies, A Report of the Workshop Sponsored by 

the Office of Research on Women’s Health, NIH Publication

No. 95-3756. Washington, D.C.: 1995.

9 U.S. Department of Health and Human Services, National

Institutes of Health, Women in Biomedical Careers: Dynamics

of Change – Strategies for the 21st Century, NIH Publication

No. 95-3565. Washington, D.C.: 1995.

10 U.S. Department of Health and Human Services, National

Institutes of Health, Office of Research on Women’s Health.

Report of the National Institutes of Health: Opportunities for

Research on Women’s Health. NIH Publication No. 92-3457.

Washington, D.C.: U.S. Government Printing Office, 1992.

working group reports

9

VOLUME 4

BACKGROUND

The 1991 workshop “Opportunities for

Research on Women’s Health” generated a

surge of new research recommendations on

issues related to the cardiovascular health of women.

Many more important questions still must be addressed,

especially through research on the molecular, cellular,

and physiological levels.

Cardiovascular disease (CVD) is the number one

killer in the United States, killing more than 954,000

Americans each year, about one person every 33 seconds. The disease is also a major cause of disability.

About 13.5 million Americans, including 6.6 million

under age 60, now live with the effects of heart attack.

In 1992, CVD accounted for 4.7 million years of potential life lost before age 75. Approximately 3.8 million

Americans, more than 900,000 of whom are under age

60, suffer from the consequences of stroke, the main

cause of permanent disability in the United States.1

More than 1 in 4 million Americans suffer from

some form of CVD, at an estimated cost of $151 billion

in 1996. The costs for patients with CVD are growing

because we are treating the disease with expensive

technology, not preventing it. Moreover, there will 

be even more cardiovascular disability in the future

because many people who have had effective treatment for coronary artery disease (CAD) and prevention of atherosclerosis between ages 40 and 60 will

develop further CVD later in life unless effective 

prevention methods are discovered.1

Cardiovascular disease is the number one killer 

of women in the United States, accounting for about 

45 percent of deaths among women. It kills almost

twice as many American women as all cancers. Heart

attacks kill more than five times as many women 

as breast cancer. Of the more than 489,700 deaths

from heart attack each year, more than 48 percent

occur in women.

An important fact to consider is that the heart

attack death rate for African-American women between

ages 35 and 74 is about twice that of white women 

and three times that of women of other races. Stroke,

America’s number three killer, kills twice as many

women as breast cancer. However, until recently, 

heart attack, stroke, and other CVDs in women 

have not been recognized as a serious problem, 

particularly by women themselves.

Women develop heart disease later in life than

men, but, at any age, heart attack in women is more

deadly. Older women who have suffered heart attacks

are twice as likely as men to die from them within a

few weeks. About 44 percent of women who have heart

attacks die within a year, whereas only about 27 percent of men die within a year. Among women who died

suddenly of coronary heart disease, 64 percent had no

previous symptoms, compared to 48 percent of men.

Other CVDs are prevalent in women. More than

87,000 of fatal stroke victims are women, representing 60.6 percent of stroke fatalities. Less prevalent 

are cases of rheumatic heart disease, an inflammatory

disease that permanently damages the heart and its

valves. Again, mortality from this disease is higher 

for women (69.9 percent) than for men.

The procedures for clinical diagnosis of CAD in

women must be improved. Research should focus 

Cardiovascular Disease/

Vascular Biology

Cochairs

Suzanne Oparil, M.D.

University of Alabama at Birmingham

David Robinson, Ph.D.

National Heart, Lung, and Blood Institute

National Institutes of Health

Rapporteur: Margaret E. Pickeral
10

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

on better descriptions of anginal syndromes, on

enhancing the efficacy of diagnostic and screening 

testing in women, and on developing alternative 

strategies for diagnosis.

In the environment of managed care, all research,

especially research on women’s health, must incorporate measurements of outcomes. The Office of Research

on Women’s Health (ORWH) should carefully assess

the therapies that are being delivered, how effectively

they are being delivered, and the outcomes that 

women experience from the results of these therapies.

Outcomes research in women’s health is needed to

influence health care policy. Funding is needed for

research on gender differences in disease outcomes

across the board.

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT

OF ORWH

Although progress has been made, there is still 

a long way to go in CVD research on women. The

1991 Report of the National Institutes of Health: Opportunities for Research on Women’s Health (“Cardiovascular Function and Disease,” pp. 171–184) made 

14 recommendations that addressed the clinical 

and psychosocial aspects of CVD. This report 

focuses on the basic science of cardiovascular 

disease as it relates to women’s health. 

The Hunt Valley report identified coronary 

artery disease as the highest priority for research 

on women’s health, and it identified sex hormones, 

particularly estrogen, as the major determinant of 

CAD risk in women. The Hunt Valley report made 

three recommendations regarding CAD:

1. The procedures for clinical diagnosis of CAD 

in women must be improved. Research should 

focus on better descriptions of anginal syndromes, enhancing the efficacy of diagnostic 

and screening testing in women, and developing alternative diagnosis strategies.

2. Studies should investigate the mechanisms that

result in women’s poorer outcomes after myocardial infarction and coronary revascularization 

procedures and how to correct these problems.

3. Research should examine the efficacy of components of the cardiac rehabilitation effort on outcome after myocardial infarction, including factors

that affect women’s success in such programs.

(Note: Portions of the remainder of this section 

have been adapted or excerpted from an article by 

Dr. Suzanne Oparil entitled “Cardiovascular Risk

Reduction in Women,” November 1, 1996, Journal 

of Women’s Health, vol. 5, with the permission 

of the publisher.)

Gender differences in CVD, from clinical practice 

to understanding basic mechanisms, have been inadequately explored in part because of the false assumption that atherosclerosis is less prevalent and more

benign in women. Gender differences appear to exist 

in areas ranging from risk-factor identification and

modification to diagnosis and treatment.

Recent attention to the high prevalence of fatal 

and nonfatal cardiovascular disease in women has

underscored the importance of lifestyle modification

and cardiovascular risk-factor reduction in this population. Recommendations for risk-factor reduction in

women are generally the same as in men, with one

major and several minor exceptions. Postmenopausal

hormone replacement therapy has a powerful effect 

on cardiovascular risk reduction, but it may be inappropriate for some women because of apparent

enhanced breast cancer risk. The utility of aspirin 

therapy in the primary prevention of CVD in women

remains to be established. Further, the benefit of, and

prescription for, lipoid-lowering therapy may prove 

to be different than men, and the benefits of antihypertensive treatment may be less. For the other risk 

factors, including smoking, diabetes mellitus, obesity,

sedentary lifestyle, and alcohol, recommendations 

are the same for both sexes.
11

VOLUME 4

Menopause and Hormone Replacement Therapy

Meta-analyses of observational studies suggest 

that a benefit of a 50-percent reduction in risk for 

heart disease occurs among postmenopausal women

taking estrogen replacement therapy. However, observational studies have the severe limitation of treatmentselection bias. Women who are taking postmenopausal

hormone replacement treatment tend to be healthier,

better educated, and more attentive to lifestyle-modification strategies for reducing cardiovascular risk and 

to have better health care.

The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial is a prospective, randomized,

double-blind, placebo-controlled trial that is assessing

differences among placebo, unopposed estrogen, and

each of three estrogen/progestin regimens on selected

heart disease risk factors in healthy postmenopausal

women. The findings after 3 years of followup provide

strong evidence that estrogen alone, or combined with

progestin, has a cardioprotective effect in postmenopausal women, particularly in those women with 

preexisting coronary disease or those who are at high

risk for developing coronary disease. Whether these

beneficial effects on cardiovascular risk factors translate

into a reduced incidence of heart disease and reduced

cardiovascular mortality rates awaits the results of

large-scale, multicenter, long-term, randomized trials,

which are in progress in the Women’s Health Initiative.

Meta-analyses suggest that there may be a 15- 

to 30-percent increase in risk of breast cancer after 

10 years of postmenopausal estrogen replacement 

therapy. There appears to be little or no risk associated with past use or short-term (5 years or less) use 

of estrogen, and there is no clear evidence that breast

cancer risk increases with increasing doses of estrogen

or different treatment regimens. Further, the Nurses’

Health Study, an observational study of 121,700 female

registered nurses, reported a 30- to 45-percent increase 

in risk of breast cancer in participants who were taking

hormone replacement therapy. The increase in risk 

was the same whether estrogen alone or an estrogen/

progestin combination was taken. Because heart disease

is so much more common than breast cancer, the impact of postmenopausal hormone replacement therapy

on lives saved by decreasing fatal heart attack rates 

has been predicted to be greater than on lives lost by

increasing breast cancer rates. It should be emphasized

that all of these figures are estimates based on observational studies that have potential sources of bias,

such as differences in rates of participation in mammographic screening. Accordingly, data from randomized

prospective clinical trials are needed to address the 

balance of benefits and risks of hormone replacement

therapy. Further, relative risks of cardiovascular disease

versus breast cancer vary greatly among women, so

decisions about postmenopausal hormone replacement therapy should be individualized.

Lipids

Low levels of high-density lipoprotein cholesterol

(HDLC), particularly in association with hypertriglyceridemia, are strong predictors of coronary heart disease in women. Average levels of HDLC are higher in

women than in men throughout adult life, although 

the gender difference is lower after middle age. It has

been postulated that HDLC may partly account for 

the gender difference in coronary heart disease risk.

Estrogens raise HDLC levels by at least two mechanisms: suppressing hepatic lipase activity, thus reducing

conversion of HDL2 to HDL3, and increasing synthesis 

of apolipoprotein. Estrogens also lower low-density

lipoprotein cholesterol (LDLC) by accelerating LDL

catabolism, probably by increasing the density of LDL

receptors. Further, estrogens increase triglyceride levels

by increasing the production of large, triglyceride-rich,

very-low-density lipoprotein (VLDL) particles. These

large triglyceride-rich VLDL particles are thought to 

be cleared rapidly from the circulation and not to be

atherogenic. Lipid effects have been hypothesized to

account for ~50 percent of the cardioprotective action

of postmenopausal hormone replacement therapy with

orally administered conjugated estrogen. In contrast,

transdermal estradiol has little or no effect on lipids. 
12

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

In the PEPI trial, all hormone replacement 

regimens produced significant increases in HDL 

cholesterol and triglyceride levels and decreases in 

LDLC levels compared with placebo. Thus, estrogen

alone or in combination with a progestin improves 

the lipid profile in postmenopausal women.

Hypertension

Elevated systolic and diastolic blood pressures are

independent risk factors for acute coronary events and

cardiovascular mortality in women. The prevalence 

of hypertension, particularly systolic hypertension,

increases dramatically with age in women. Whether 

the menopause per se contributes to the age-related

increase in blood pressure in women is controversial.

Antihypertensive treatment is effective in preventing heart attack and stroke in the general population 

of hypertensives, but the magnitude of the benefit is

less for preventing coronary events than stroke. This 

is particularly true among women, in whom most

reported studies have shown no decrease in the incidence of coronary heart disease with antihypertensive

treatment, with the exception of women with isolated

systolic hypertension.

Smoking

Cigarette smoking produces a dose-related 

increase in cardiovascular risk in women as well as 

in men. This increased risk is reversible with smoking cessation, reaching the level of risk of nonsmokers

within 3 to 5 years regardless of the amount smoked,

duration of smoking, or age at cessation. More vigorous efforts are needed to discourage smoking among

women and to prevent smoking by girls.

Diabetes Mellitus

Diabetes is a more important risk factor for coronary disease in women than in men. The Nurses’

Health Study showed that maturity onset diabetes 

was associated with a threefold to sevenfold increase 

in risk of a cardiovascular event. Further, after 45 years 

of age, women are twice as likely as men to develop

diabetes mellitus. Although the mechanisms by which

diabetes accelerates the natural history of vascular disease are poorly understood, there are clear interactions

with other modifiable risk factors, such as hypertension, lipid abnormalities, obesity, and smoking.

Obesity

Overweight increases the risk of coronary heart

disease twofold to fourfold in women. The magnitude 

of the excess risk is directly proportional to the excess

body mass. This is a growing public health problem, 

as the prevalence of overweight (body mass more 

than 20 percent over the upper limit of normal) in 

the United States has increased from 25 to 33 percent 

in the past decade. The excess cardiovascular risk of

adiposity is related in part to effects on lipid levels, 

glucose tolerance, and blood pressure and in part 

to other poorly understood mechanisms. The best

approach to obesity is prevention.

The distribution of body fat may also be associated

with risk of coronary heart disease. Excess abdominal

fat appears to confer a high risk of coronary heart disease in both sexes. Among women, coronary risk is

greatly increased when the waist-to-hip ratio is more

than 0.8. It has been postulated that intra-abdominal

fat has effects on lipid metabolism that result in hypertriglyceridemia, reduced HDL cholesterol levels, and

insulin resistance. Observational studies have related

abdominal adiposity in women to a number of cardiovascular risk factors, including hypertension, physical

inactivity, and smoking. 

Sedentary Lifestyle

The effects of exercise on coronary disease and

coronary risk have been studied far more extensively 

in men than in women. However, preliminary evidence

from small prospective and case-control studies in

women and estimates derived from a meta-analysis of

studies based largely on men suggest that physically

active women have a 50-percent reduction in coronary

disease risk compared with inactive women. Further,

prospective data from the Healthy Women Study 
13

VOLUME 4

indicated that exercise had beneficial effects on 

important risk factors, including weight and HDL 

cholesterol levels, in perimenopausal women. Large,

long-term prospective studies are needed to determine

whether the favorable effects of exercise on cardiovascular risk factors in women translate into a reduced

incidence of coronary disease.

Alcohol

Case-control studies and cohort studies have shown

that moderate (one or two drinks per day) alcohol use

protects against coronary heart disease in women and

men, but the beneficial effects must be balanced against

the health hazards of alcohol, including increased

blood pressure and increased risk of hemorrhagic

stroke, breast cancer, and addiction and abuse. Accordingly, alcohol is not recommended for cardioprotective

purposes in women (or men) who are nondrinkers.

Aspirin

Aspirin reduces (by ~25 percent) the recurrence

rate of myocardial infarction, stroke, and death from

cardiovascular causes in women, as well as in men,

with established coronary artery disease. In contrast,

data on the efficacy of low-dose aspirin in the primary

prevention of coronary heart disease in women, all

derived from observational studies, are inconsistent.

Studies in progress are assessing the risks and benefits 

of aspirin in the primary prevention of coronary heart

disease and stroke in women.

Antioxidants

Antioxidant vitamins, including vitamins E and 

C, and beta carotene have shown inconsistent benefit

and some increased risk (hemorrhagic stroke) in men.

The recent evidence that antioxidant vitamins may 

have harmful effects, and appear not to be beneficial 

in some settings, underscores the need for further

study before the widespread use of these agents can 

be recommended for heart disease prevention.

GAPS IN KNOWLEDGE

Although progress has been made in controlling

CVD, there is still a long way to go in the prevention 

of CVD in women. In the near future, it will become

necessary for research efforts on cardiovascular diseases, immunology, and infectious disease to merge.

For example, information is increasing about whether 

or not agents, such as chlamydia, may play an intimate role in atherogenesis.

Evaluation of Chest Pain in Women

Women with CVD are generally older and sicker

than men and do not respond to treatment as well as

men. The reasons for this still need to be elucidated.

Women report symptoms of ischemia differently than

men and responses to diagnostic tests for ischemic

heart disease are different between the sexes. For example, silent ischemia and silent myocardial infarctions

occur commonly in women, perhaps due to the presence of diabetes, which greatly enhances CAD risk in

women. Further, chest pain in the absence of identifiable disease in the epicardial coronary arteries is a

major problem in women. Since diagnostic standards

developed for men are generally applied to women,

diagnosis of CVD is difficult for women. Additional

research is needed to refine the specificity/sensitivity 

of diagnostic testing for CAD in women.

Atherosclerotic Process in Men and Women

There are major differences between men and

women in the evolution of atherosclerosis and the 

risk of disease, especially at the cellular level. The 

need to fill the gap in knowledge and fundamental

understanding of cell biology is certainly an issue in 

the treatment of atherosclerosis. It is highly possible

that estrogen is a part of the problem, but the fact 

that you can treat women with estrogen much more 

successfully than men, regardless of dose, is an issue 

that should be addressed. 
14

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

There is mounting evidence that atherosclerosis 

represents an inflammatory response to infectious

agents such as chlamydia or to noninfectious agents

such as oxidized low-density lipoprotein. Some 

inflammatory disorders are more common in women,

particularly premenopausal women, than in men. 

For instance, in lupus arteritis, it is believed that 

estrogen has beneficial effects in the vessel wall. 

Therefore, there is a need for more knowledge 

about the interaction of estrogen and the inflammatory process, including inflammatory cell expression 

and expression of cell-adhesion molecules. 

Stroke

Sixty percent of stroke fatalities are among women.

Twice as many black women as white women die of

stroke in all age groups. Multiple pregnancies may

increase the risk of cerebrovascular disease and stroke

through the mechanism of insulin resistance. Diabetes

triples the risk of stroke in women. The increased risk

of subarachnoid hemorrhagic and ischemic stroke in

women who smoke may be reversed in 2 to 4 years

after smoking ceases.

Lack of Psychosocial Support After 

Myocardial Infarction

Women with a diagnosis of myocardial infarction

generally have poor outcomes. The psychosocial impact on these women, who usually must return home

and resume the routine of running a household, is not

known. For example, there is a gap in knowledge

about women who suffer depression after a diagnosis 

of CVD. Women are four times more likely to suffer

from depression than men. Depression increases 

mortality in women from approximately 4 percent to

greater than 40 percent. Depression not only creates

social problems, it can also alter chemicals in the brain.

Diabetes and Cardiovascular Disease

Insulin-dependent diabetes mellitus is an important cause of premature CVD among young men and

women under 45 years of age. Cardiovascular disease 

is especially high among premenopausal women who

have insulin-dependent diabetes mellitus and smoke

cigarettes. Studies are needed to ascertain why diabetes

increases the risk for CVD among premenopausal

women. Data are needed on the efficacies of medical

and revascularization therapy and on exercise rehabilitation for coronary heart disease failure and stroke.

The interaction between diabetes, estrogen therapy, and CAD in women is not known. It is unclear

whether estrogen replacement therapy effectively 

protects postmenopausal diabetic women from 

developing CVD. More clinical data are needed, as 

well as more basic information about the effects of 

estrogen on the biology of the diabetic blood vessel.

Lipid Profiles and Obesity

The major risk factors for coronary heart disease

and stroke are similar for men and women. These

include high levels of LDLC, low levels of HDLC,

smoking, high blood pressure, diabetes, obesity, and

physical inactivity. The gender differences appear to 

be in the magnitude of the increased risk for disease 

at similar risk-factor levels. Estrogens have direct 

effects on the arterial wall and appear to enhance 

the activity of LDL receptors, resulting in lower 

levels of LDLC among premenopausal women. As 

the estrogen level and ovarian function decline, postmenopausal women develop higher LDLC levels. This

increase in LDLC in older women contributes to the

increase in atherosclerosis and coronary heart disease. 

Weight gain is common in American women

between the ages of 30 and 50 years. The distribution of body fat is different in women than in men. 
15

VOLUME 4

For example, central obesity is more common in

African-American women than in white women, 

but in one study, the body mass index and waistto-hip ratio were predictors of cardiovascular 

death only for white women.

Vascular Effects of Estrogens

Large gaps persist in the knowledge about the 

vascular effects of estrogens. There is evidence that 

various estrogen preparations (natural versus synthetic, orally versus percutaneously administered) have

different vascular effects. The mechanisms of their 

differences should be studied further. It is important 

to do research that will close the gap of knowledge

about whether hormone replacement therapy increases

the risk for breast cancer while decreasing risk for

CVD. Women, in general, see coronary disease as a

problem of very old age, but they see breast cancer 

as a disease that affects women at younger ages. 

RESEARCH 

RECOMMENDATIONS

The consensus of the working group was that an

overall recommendation should be made for genderspecific evaluation in all areas of CVD discussed in 

this report. Also, for certain CVDs, a longitudinal 

study should be conducted that is specific to certain

racial or ethnic groups. Because women communicate their symptoms differently, it is important that 

all cardiovascular research outcomes identify genderspecific diagnoses and treatments.

Coronary Artery Disease

• Study the cellular aspects of coronary artery disease in men and women to determine if this is 

really a different disease in women than in men.

• Determine the basic mechanism of action of 

both endogenous and exogenous reproductive 

hormones in the development of atherosclerosis.

• Determine if differences in hormonal measures,

dietary factors, and genetic characteristics influence

the changes in risk factors and the progression 

of atherosclerosis.

• Design studies to determine the qualitative aspects

of angina in women and men.

• Determine if women have subtle asymptomatic

limitations in coronary reserve.

• Determine how response to diet modification 

is affected by age, status, hormone replacement

therapy, and baseline lipid lipoprotein levels.

• Determine the outcomes of antihypertensive 

therapy by gender.

Cerebrovascular Disease 

• Research should incorporate outcomes measurement in research. Scientists should carefully assess

existing therapies, how effectively they are being

delivered, and the outcomes that women are 

experiencing from these therapies.

• Determine why stroke occurs in African-American

women at an earlier age than in white women.

• Identify other potentially reversible stroke risk 

factors in addition to smoking.

• Determine why there is a later onset of stroke,

other CVD, and CHD in women than in men.

• Determine the extent of various venous disorders

seen predominantly in women, and whether these

can be prevented.

Chest Pain and Arrhythmias in Women

• Define the mechanisms of chest pain in the 

absence of epicardial CAD in women.

• Improve methods for diagnosing ischemia 

in women.
16

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Prevention and Education Strategies

• Expand research to include strong behavioral 

models. Encourage medical schools to expand 

their curricula by fostering research in this area.

• Educate health care providers about the symptoms

of CVD in women. Provide disease-by-disease

information on prevention and education.

• Educate the public that heart disease is the 

major killer of women.

• Educate the public on the hazards of smoking 

as it relates to cardiovascular disease.

• Develop educational strategies aimed at health 

care providers, especially nurse practitioners.

• Provide information on the large numbers of

women who do not report heart palpitations 

to their health care providers.

• Focus on prevention strategies, particularly 

nutrition and body weight.

• Educate physicians, nurses, and the public 

about the nature of CAD in women and its 

unrecognized importance.

Vascular Mechanisms with Hormone 

Replacement Therapy

• Study hormonal impact on endothelial function

both in pre- and perimenopausal women.

• Develop a replicate mechanism for hormone 

therapy for women as well as for men.

• Define a good animal model for testing 

hormone therapy.

• Look at the interaction between diabetes and 

CAD in women. Develop research programs 

to determine if estrogens protect diabetic 

women against the prospect of atherosclerosis or other vascular defects.

• Compare the different estrogens (both 

human and nonhuman) to determine 

whether there is an advantage of one 

over the other.

• Study what effect estrogen has in 

molecular biology.

• Develop research programs to study 

whether different vascular beds respond 

differently to estrogen therapy from a 

vascular biology standpoint.

• Revisit the question, “Do the risks of breast 

cancer outweigh the risk of heart disease 

when administering hormone replacement 

therapy in women?”

• Increase the understanding of the various 

types of hormones used for basic therapy.

• Determine if estrogen and estrogen-progestin 

combinations alter the risk of coronary 

heart disease.

• Determine the relation of estrogen to other 

risk factors on vasoregulation and other 

atherosclerotic processes.

• Determine the metabolic effects of estrogen 

replacement therapy or hormone replacement therapy on patients with other 

metabolic abnormalities.

• Determine the efficacy of hormone 

replacement therapy in preventing 

CVD in postmenopausal women.

• Determine why HDLC levels are higher 

in women after puberty compared with 

men. Are they determined solely by 

sex-steroid metabolism?

• Determine if hormonal or psychosocial 

factors explain why childless women 

have a higher risk of sudden death.
17

VOLUME 4

• Identify the effect of estrogen therapy on the 

reversal and progression of stroke and peripheral 

vascular disease.

Comparative Atherosclerosis in Men and Women

• Conduct research to determine if the rise in 

the LDLC level and the development of atherosclerosis in women can be prevented.

Gender-specific Secondary Analysis in Hypertension

• Develop better knowledge and criteria for 

studying hypertension in women.

Prevalence and Clinical Manifestations of 

Peripheral Vascular Disease

• Conduct research to determine what level 

of blood pressure should be considered 

normal (140/90 or 120/80).

• Obtain more information about the different 

categories of active hypertensive medications 

and in which groups these medications might 

be most effective.

• Develop better methods to identify those patients

who would benefit from heart transplants.

• Conduct prevalence and clinical manifestation

studies for peripheral vascular disease. Determine 

if there are gender differences in peripheral 

vascular disease.

Comparative Etiology of Heart Failure in Men 

and Women

• Conduct studies to determine if the etiologies 

of heart failure are different for women and 

for men.

• Determine if progress has been made in understanding why women diagnosed with myocardial

infarctions have poor outcomes.

• Determine what changes occur in risk factors 

during the peri- and postmenopausal periods 

in nonwhite populations.

• Determine how the patterns of obesity and 

fat deposition relate to CVD in women.

• Identify the determinants of weight gain 

in women.

• Identify the most effective approaches to 

preventing obesity among minorities.

• Determine if there is an association between 

number of pregnancies and weight gain.

19

VOLUME 4

Neuroscience, Behavior,

and the Health of Women

Across the Life span

BACKGROUND

I

n recent years, advances in basic and clinical neuroscience have enhanced the ability of researchers

and clinicians to understand the neurobiology

underlying diseases and conditions such as Alzheimer’s

disease, anxiety disorders, chronic pain, depression,

epilepsy, multiple sclerosis, Parkinson’s disease, schizophrenia, and stroke. Such advances have occurred, in

part, as a result of improvements in the tools and technologies now available to study and map the brain and

its functioning in health and disease. Understanding

brain disorders has also benefited from an increased

focus on the role of estrogen, progesterone, dopamine,

serotonin, and other naturally occurring chemical 

substances in cognition and emotion.

Through the use of positron emission tomography

(PET), single photon emission computerized tomography (SPECT), magnetic resonance imaging (MRI) and

spectroscopy (MRS), functional MRI (fMRI), and similar methods, neuroscientists have begun to examine in

vivo the physiology, neurochemistry, and anatomy of

the human brain. With the increased attention given 

to research on women’s health, and gender differences

in health and disease, studies have begun to focus on

sex and gender differences in brain structure and function that may contribute to differences in cognitive and

emotional processing.1 Studies have also identified sex

differences in the manifestation of brain disorders and

the influence of reproductive endocrine disorders 

in women and men suffering from such diseases 

as epilepsy.2,3 Research has also begun to focus on 

the influence of hormonal states on cognition and

affect in health and disease.4

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT

OF ORWH

Sex Differences in Cognition and Effects of Hormones

Scientific evidence on the effects of sex hormones

on adult cognition has emerged since the 1991 meeting organized by ORWH in Hunt Valley, Maryland.

Through basic science and clinical research, it is now

known that varying estrogen and progesterone levels,

across the menstrual cycle and across the life span, 

can influence an individual’s performance on a 

number of cognitive tasks.

Estrogens have been shown to have numerous

effects on the brain, beginning at gestation and continuing into adulthood. Many of these effects implicate

areas of the brain that are involved in memory processes and their alterations over the life span in healthy

people, and this is important for understanding the

pathophysiology and consequences of neurodegenerative diseases.5 Preliminary studies conducted in

recent years have shown that the decline of estrogen/

progesterone levels at menopause is associated with

Cochairs

Raquel E. Gur, M.D., Ph.D.

University of Pennsylvania

Constance W. Atwell, Ph.D.

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Rapporteur: Mary Chunko
20

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

diminished cognition, but that estrogen replacement

therapy (ERT) in postmenopausal women can enhance

performance of cognitive functions.6 In addition, there 

is now evidence that ERT can prevent or delay the

onset of Alzheimer’s disease and stroke by affecting

nerve-growth-factor systems, particularly cholinergic

neurons in the basal forebrain.7

Recent research on animal and human subjects 

is challenging the long-held assumption that the adult

brain does not undergo changes in its structure, particularly in relation to the actions of circulating hormones.

It is now clear that estradiol and progesterone have

important effects on adult brain structure and function.

Animal studies have documented how the density of

dendritic spines on hippocampal CA1 pyramidal cells

is dependent on circulating estradiol and progesterone

and fluctuates naturally during the 5-day estrous cycle

of the adult rat.8 In one of these studies, increased

spine numbers were accompanied by increased numbers of synapses on spines. Changes of synaptic density

in the hypothalamus are responsible, at least in part,

for the cyclicity of sexual behavior,9 while the cyclicity 

of synapses in the hippocampus may influence spatial

reasoning and memory.10

In humans, such cyclic fluctuations in gonadal hormones are associated with cyclic changes in performance

on a variety of cognitive and motor tasks.11 Other research, conducted in recent years, suggests that estrogen

and progesterone modification of dendritic spines in

the CA1 region of the hippocampus may contribute 

to cognitive changes during menopause, as well as 

temporal lobe epilepsy associated with polycystic

ovaries or hypogonadotrophic hypogonadism.12

Sex Differences in Manifestations of Brain Disorders

Several observers of the effects of brain disorders

have documented sex differences in the frequency and

severity of several brain disorders (e.g., stroke, depression, schizophrenia). However, more recent work indicates that such differences are ubiquitous and may help

shed light on the pathophysiology. Several examples

may help illustrate how such research can have both

theoretical and clinical implications. 

Sex differences were noted in a prospective Finnish

study that examined diabetes mellitus as a risk factor

for death from stroke, with women being at a higher

risk than men. Similarly, women with myocardial

infarction, treated with thrombolytic therapy, have 

a higher incidence of hemorrhagic stroke. This may

relate to increased rates of cerebral blood flow in

healthy women compared to men.

Sex differences have also been documented in the

manifestations of Alzheimer’s disease (AD). Women 

are at a higher risk for late-onset familial AD, and this

might be related to gender differences in apolipoprotein E epsilon4 (EPOE) heterozygous genotype, which 

is more common in women. Women with AD perform

worse than men with AD on measures of semantic

memory and language, whereas healthy women perform

better than healthy men on these tasks. Neuropsychiatric manifestations in AD are also more severe in

women, which is consistent with the greater frequency

and severity of depression experienced by women.

In contrast, schizophrenia manifests itself less

severely in women than in men. The symptoms occur

later in life for women than for men, are less severe,

have a milder course, and show a better outcome. It 

is noteworthy that this difference may be age related

since elderly women with schizophrenia have more

severe symptoms than elderly men. These differences

have been linked to sex differences in neurobiological

measures and their correlations with disease factors.

Sex Differences in Response to Treatment of Diseases

The increased recognition of sex differences in

health and brain disease has implications for examining

sex differences in response to treatment. The literature 

is limited, however, since most studies were conducted

with only men or were not evaluated for sex differences. Integrating research that examines sex differences
21

VOLUME 4

in treatment with research on sex differences in 

disease presentation is essential. Some preliminary 

studies are noteworthy.

Studies suggest that the effectiveness of treatment for chronic pain may be different for women 

and men. Basic research on pain has shown that 

estrogen appears to induce analgesia through a 

different pathway in female mice than in male 

mice. Thus, drugs developed in studies with male

research models, and tested in males, may not 

be as effective in relieving pain in females.13

Other studies using animal models and humans

have demonstrated that pregnancy and parturition 

are associated with elevated pain thresholds in the

mother.14 During hormone-simulated pregnancy, 

an opioid-mediated maternal analgesia involving 

the spinal chord dynophin/kappa-opioid system 

attenuates the pain associated with late pregnancy 

and labor.15 Such research could lead to the development of new interventions that are more effective 

in mitigating pain in both women and men.

Animal work suggests that the development 

of drugs for the treatment of stroke, for example,

should evaluate potential sex differences very carefully. In the rat, N-methyl-D-aspartate antagonists 

have been reported to induce greater age-associated 

neuronal necrosis in females than males.

Methodological Developments

The number of studies in which sex and gender

differences are included as study variables has increased

since 1991. These range from studies focusing on the

differences in the structure and functioning of the 

brain in males and females to research on the effects 

of hormones on the brain, the central and sympathetic

nervous systems, and brain disease manifestation and

treatment in women and men. There is convergence 

of both basic and clinical neuroscience methodology

that enables examination of sexual dimorphism 

developmentally.

Animal work provides the foundation for integrative research on neuroanatomy, neurochemistry,

neuroendocrine function, and neurophysiology. The

developmental perspective examines sex differences

across these variables in relation to brain development

and maturation. In clinical neuroscience, the availability of neuroimaging techniques for quantitative

measurement of brain anatomy and function (physiology, neuroreceptors) provides an opportunity to spell

out the major brain parameters that show sex differences. These measures, when taken concomitantly 

with clinical and neurocognitive assessment, can 

yield a powerful tool that will help in identifying 

the mechanisms for sex differences in healthy brain

function and in specific disease states. Perhaps as

important, these technologies can offer and test

hypotheses that have implications for intervention. 

GAPS IN KNOWLEDGE

While encouraging progress has been made 

in recognizing that sex differences in brain function

exist both in health and disease, the scientific base is

still at the very beginning and the gaps in knowledge

are wide. Many questions remain about sex differences

in the normal and abnormal development and functioning of the nervous system, and there is a need for

research that focuses on sex differences in brain function and cognition across the life span. Such research

must be more than merely descriptive, and for that 

it has to be interdisciplinary and focus on health and

pathology. Further studies are also needed to address

genetic regulation of neural functioning in both sexes,

as well as to determine hormonal influences on brain

development and plasticity.

CHANGE IN QUESTIONS

SINCE HUNT VALLEY 

Over the past decade, the number of studies 

focusing on sex and gender differences in brain 

health and disease have increased. More recently 
22

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

in the neurosciences, there has been a major shift 

away from descriptive questions and studies of sex 

differences in normal and abnormal brain function 

and a movement toward questions and studies aimed

at determining underlying mechanisms that influence

brain function. This shift reflects both an increase in

understanding that sex and gender differences exist 

and improvements in the tools now available to

researchers for documenting brain function. 

At the same time, investigators have enlarged the

scope of studies, moving away from questions and

studies confined to a single discipline and toward 

those that integrate the study of cognition, emotion,

endocrinology, and immunology. Such integrative, 

multidisciplinary approaches allow researchers to

determine how biological mechanisms may be tied 

to changes in cognition and affect over the life span.

Such work is germane for insight into mechanisms 

and consequences of brain disorders, and how 

sex-related factors may modulate their effects 

on cognitive and behavioral changes.

To better understand normal brain development

and function across the entire life span, researchers

have therefore begun to focus increasingly on the 

study of healthy brain functioning in women and 

men at different life stages. This reflects a larger 

trend in the neurosciences and in biomedical science 

to exert greater efforts in documenting and understanding the range of healthy variability as a means 

of sharpening the sensitivity of diagnostic tools to 

the effects of brain pathology. 

RESEARCH 

RECOMMENDATIONS

Working group participants made the following

recommendations for research on sex and gender in

neuroscience and behavior:

• Undertake multidisciplinary studies of healthy

women across the life span to determine sex differences in normal development as these affect:

– the brain and neural development;

– brain function; and

– cognition and emotion.

• Study the effects of hormones on cognition 

and emotion within different phases of the 

menstrual cycle and at different reproductive 

stages (especially perimenopause).

• Study sex differences across brain health 

problems (e.g., epilepsy, multiple sclerosis,

Alzheimer’s, depression, sleep disorders, 

schizophrenia), including:

– presentation, course, and prognosis;

– compensatory mechanisms; and

– response to treatment, including hormones and

other therapeutics (e.g., drug interactions).

• Study sex differences in brain plasticity and 

development, including implications for rehabilitation and strategies for learning.

• Undertake studies to establish sex differences 

at the molecular level (e.g., preclinical investigations of novel ligands for estrogen receptors).

• Study the neurogenetics of sex differences as

expressed in brain function, pathology, and complex behaviors (e.g., non-Mendelian expression 

of X-chromosome effects such as imprinting).

• Develop appropriate methodologies to advance 

the research agenda through:

– longitudinal designs (e.g., within and across 

the menstrual cycle in the same women);

– modification of instruments that measure 

symptoms and function and that take into

account variability across the menstrual 

cycle and reproductive stages;
23

VOLUME 4

– multidisciplinary assessments of individual

patients that take into account medical, environmental, sociological, and psychological 

variables; and

– movement away from difference/deficit 

models of brain function and behavior 

to models of variability.

References

1 Gur, R., et al. 1995. Sex differences in regional cerebral

glucose metabolism during a resting state. Science

267:528–31.

2 Stoupel, E., J. Martfel, and Z. Rotenberg. 1991. Admissions

of patients with epileptic seizures (E) and dizziness (D)

related to geomagnetic and solar activity levels: Differences

in female and male patients. Med Hypotheses 36:384–88. 

3 Ahern, G.L., et al. July 1994. Paraneoplastic temporal lobe

epilepsy with testicular neoplasm and atypical amnesia.

Neurology 44(7):1270–74; Heroz, A.G. 1996.

4 Temporolimbic epilepsy and polycystic ovary syndrome.

Fertil Steril 65(1):210–11.

5 Kimura, D. and E. Hampson. 1994. Cognitive pattern in

men and women is influenced by fluctuations in sex hormones. Curr Dir Psychol Sci 3:57–61; Drislane, F.W., et al.

February 1994. Altered pulsatile secretions of luteinizing

hormone in women with epilepsy. Neurology 44(2):

306–310; Halbreich, U., et al. 1995. Possible acceleration

of age effects on cognition following menopause. J Psychiatric Res 29(no)3:151–63. 

6 McEwen, B.S., et al. 1995. Oestrogens and the structural

and functional plasticity of neurons: Implications for memory, aging, and neurodegenerative processes. Ciba Found

Symp (review) 191:52–66, (discussion) 191: 66–73.

7 Halbreich, et al. 1995. Possible acceleration of age effects,

151–63. Hampson, E. and D. Kimura. 1992. Sex differences and hormonal influences on cognitive function in

humans. In Behavioral Endocrinology, eds. J.B. Becker, S.M.

Breedlove, and D. Crews. Boston: MIT Press; Sommer, B.

1992. Cognitive performance and the menstrual cycle. In

Cognition and the Menstrual Cycle, ed., J.T.E. Richardson.

New York: Springer-Verlag.

8 Gibbs, R.B. 1994. Estrogen and nerve growth factor-related

systems in the brain: Effects on basal forebrain cholinergic

neurons and implications for learning and memory processes and aging. In Hormonal Restructuring of the Adult

Brain: Basic and Clinical Perspectives, eds. V.N. Luine and

E.F. Hardings (Annals of the New York Academy of Sciences, 1). New York: New York Academy of Sciences.

9 McEwen, B.S., et al. 1994. Resolving a mystery: Progress 

in understanding the function of adrenal steroid receptors

in hippocampus [review]. Prog Brain Res 100:149–55.

McEwen, B.S., et al. 1995. Oestrogens and the structural

and functional plasticity of neurons: Implications for memory, aging, and neurodegenerative processes. Ciba Found

Symposium 191:52–66, (discussion) 191:66–73; McEwen,

B.S. and C.S. Wooley. 1994. Estradiol and progesterone

regulate neuronal structure and synaptic connectivity in

adults as well as developing brain. Exp Gerontol

29(3–4):431–36.

10 Wooley, C.S. and B.S. McEwen. 1993. Roles of estradiol

and progesterone in regulation of hippocampal dendritic

spine density during the estrous cycle in the rat. J Comp

Neurology 336(2):293–306.

11 McEwen. 1994. Estradiol and progesterone, 431–36.

12 McEwen. et al. 1994. Resolving a mystery, 149–55.

13 Mogil, J.S., et al. 1993. Sex differences in the antagonism

of swim stress-induced analgesia: Effects of gonadectomy

and estrogen replacement. Pain 53:17.

14 Dawson-Basoa, M.B. and A.R. Gintzler. 1993. 17 Betaestradiol and progesterone modulate an intrinsic opioid

analgesic system. Brain Res 601(1–2): 241–45.

15 Medina, V.M., M.E. Dawson-Basoa, and A.R. Gintzler.

1993. 17 Beta-estradiol and progesterone positively modulate spinal chord dynorphin: Relevance to the analgesia 

of pregnancy. Neuroendocrinology 58(3): 310–15.

16 Ibid.

Immunology

BACKGROUND

At the Opportunities for Research on Women’s

Health workshop — sponsored by the Office

of Research on Women’s Health (ORWH) 

and convened in Hunt Valley, Maryland, in September

1991 — participants emphasized the importance of

intensified research on immunologic diseases. Since

then, many discoveries have been made about the 

intricate functioning of the body’s immune system,

making the past 5 years an exciting time in the field 

of immunology. The new understanding of the immune

system will lead scientists to develop techniques to

turn on the immune response to protect against infectious diseases and to turn off the immune response to

protect against the allergic and autoimmune diseases.

Many advances have already been made in the clinical

diagnosis of and therapies for the immunologic diseases, and many more are on the horizon. 

Even more importantly, recent basic science

research has shown that immune mechanisms appear 

to complicate many diseases, although their primary

cause has nothing to do with the immune response.

Thus, the scope of immunology has expanded far beyond

a study of the immunologic diseases to include a study

of atherosclerosis and cancer, the two leading causes 

of death in the United States for women and men. 

Nevertheless, many gaps remain, among the biggest

of which is the lack of understanding of the causes of

the autoimmune diseases and of why they affect women

disproportionately (see Table 1). However, like the Chinese,

who use the same ideogram to express the concepts of

both crisis and opportunity, immunologists recognize

that the many gaps now existing in immunology present great opportunities for making further advances in

basic science and clinical intervention. Many immunologists in academia and in pharmaceutical and biotechnology industries believe that most of these issues will

be significantly better understood in the coming years.

Participants in the Working Group on Immunology discussed the advances in immunologic research

since ORWH was established in 1990 and made several

recommendations for further research in those areas

where gaps remain.

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT

OF ORWH

Since the Hunt Valley workshop, the understanding

of the processes of the immune system has advanced

greatly. Many of these advances have already led to

more effective clinical interventions for the immunologic diseases. Advances have also been made in the

understanding of the epidemiology and natural history

of several diseases and in the impact of behavior and

education on prognosis and response to therapy.

Technological Advances 

Many of the advances in immunology in the last 

5 years are the result of new technologies, such as the

genetic manipulation of mice and other animals and

the use of molecular biology techniques to identify 

disease-susceptibility genes.

Cochairs

Susana Serrate-Sztein, M.D.

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

National Institutes of Health

Betty Diamond, M.D.

Albert Einstein College of Medicine

Donna M. Murasko, Ph.D.

Allegheny University of the Health Sciences

Rapporteur: Wanda Avila

25

VOLUME 4
26

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

The development of techniques for the genetic

manipulation of mice and other animals has greatly

increased understanding of how the immune system

works. Since at least 99 percent of the genes in mice

and humans are the same and serve quite similar 

purposes, much of what has been learned about 

the various molecules and interactions in the mouse 

can now be tested in human beings.

Mario R. Capecchi and others at the University of

Utah recently developed the technology for “knocking

out,” or completely inactivating, a particular gene in

mouse embryos to determine the function of the gene.

For example, if the researcher knocks out in the mouse

embryos a particular gene involved in making antibodies, the researcher can then examine the immune

response of the newborn mice in the absence of antibody production. The technique also makes possible

targeted mutation by which researchers can insert a

mutated copy of a selected cellular gene into cells. 

This technology can lead to mouse mutations, such 

as those that exist in certain diseases, and permits “clinical” trials 

in a mouse-disease model. This

technology also allows scientists 

to determine whether a mutant

gene can cause the disease.2

The use of molecular biology

techniques has also provided a great

deal of information on the mechanisms of the immune responses.

Using these techniques, scientists

are able to develop specific vaccines

against microorganisms that cause

illness by identifying them and isolating the protein, or series of proteins, that give rise to a protective

immune response. Once the protein

and the gene encoding it have been

isolated, protein- or DNA-based

vaccines can be developed to

expose individuals to the specific

element rather than to the entire,

potentially pathogenic organism.

This technology is now being applied to the identification of self proteins that are targeted in autoimmune

disease and to allergenic proteins that lead to asthma

and other allergic diseases.

Advances in Etiology and Pathogenesis

With the help of the new technologies, various 

initiatives have been developed in the last 5 years to

elucidate the etiology and pathogenesis of immune 

diseases.3 These initiatives have had important ramifications for a number of diseases — asthma, autoimmune diseases, infectious diseases, and even cancer 

and arteriosclerosis. Some of the areas in which major

strides have been made are the following: 

Histocompatibility Complex (MHC) Molecules. As a

result of the new understanding of MHC molecules, 

a class of proteins essential for generating T-cell responses, scientists are now able to obtain a killer T-cell

response to invading pathogens by giving a specific

vaccine or by injecting DNA that encodes a foreign

TABLE 1 Estimated Number of U.S. Residents with Selected Autoimmune Diseases 

in 1996, by Gender*

Female Male Total

Addison’s 12,335 1,000 13,335

Chronic active hepatitis 1,020 136 1,156

Glomerulonephritis (primary) 33,408 72,494 105,902

Graves/hyperthyroidism 2,678,449 370,187 3,048,636

Insulin-dependent diabetes¥ 70,320 76,572 146,892

Multiple sclerosis 99,122 55,156 154,278

Myasthenia gravis 9,880 3,709 13,589

Pernicious anemia 266,303 133,152 399,455

Polymyositis/dermatomyositis 8,983 4,480 13,462

Primary biliary cirrhosis 8,189 1,043 9,232

Reiter’s syndrome 28,036 1,401,784 1,429,820

Rheumatoid arthritis§ 1,297,978 438,120 1,736,099

Scleroderma§ 3,527 298 3,825

Sjögren’s syndrome 35,726 2,382 38,108

Systemic lupus erythematosus 55,585 7,467 63,052

Thyroiditis/hypothyroidism¶ 1,410,554 79,817 1,490,371

Uveitis 2,319 2,319 4,637

Vitiligo 554,488 505,072 1,059,560

Total** 6,745,909 3,190,660 9,936,568

* In a population of 264,755,000 unless otherwise indicated.

¥ In a population of 76,494,000 individuals <20 years of age.

§ In a population of 202,939,000 individuals >16 years of age.

¶ In a population of 188,557,000 individuals >19 years of age.

** Totals may vary due to rounding.

Source: Jacobson, D.L., et al. Epidemiology and population burden of selected autoimmune diseases in

the United States. Baltimore: Johns Hopkins University.1
27

VOLUME 4

protein. Understanding the structure of the MHC 

molecules could lead to the development of molecules that will block unwanted immune responses.

Peter C. Doherty and Rolf M. Zinkernagel won the

1996 Nobel Prize in Medicine for their pioneering 

work on MHC molecules.4

Mucosal Immunity. The new understanding of

mucosal immunity has helped researchers understand

how the oral administration of antigens leads to

immune responses that differ from responses to antigens administered in other ways. Understanding the

body’s tolerance of oral antigens has important implications for the treatment of various diseases, such as

multiple sclerosis, and is leading to new vaccines

against infectious diseases and new therapies 

against autoimmune and allergic diseases.5

Mechanisms of Immunologically Mediated Tissue

Injury. The susceptibility of targeted organs to immunemediated tissue injury varies among people. Consequently, some people with autoreactivity develop

autoimmune diseases, while other people do not.

Genetic studies are beginning to reveal the basis for 

target-organ susceptibility in different diseases.6

Interaction Between Immune System and Extracellular

Matrix. Tim Springer’s pioneering studies on a family

with an immunodeficiency syndrome led to the identification of adhesion molecules, integrins and selectins,

on all cell surfaces. Understanding how these molecules are regulated, and how the cell matrix differs 

in health and disease, has led to new information on 

the movement of immune cells to sites of infection 

or tissue injury.7

Cell Signaling Cascades. When a T cell finds a

matching antigen on an antigen-presenting cell that

offers the appropriate signals, or when a B cell encounters antigen in the presence of T-cell help, tryosine

kinase enzymes are activated, initiating a cascade of

other chemical changes as the T cell (1) enlarges and

divides, thereby increasing the number of cells that

react to the antigen, and (2) secretes lymphokines to

inhibit the pathogen or to recruit other cells to join 

in the immune response. Multiple molecular components of signaling cascades have been identified, 

and molecules capable of blocking these cascades 

have been found or engineered.8

T- or B-Cell Tolerance. Immunologists have long

known that two of the mechanisms that prevent T 

or B cells from attacking the body’s healthy tissues are

(1) clonal deletion, the physical elimination of lymphocytes that recognize the body’s molecules during their

development, and (2) immunoregulation, the generation

of regulatory cells that weaken harmful or inappropriate lymphocyte responses. Recently, immunologists

have identified a third mechanism, anergy, which shuts

down specific sets of T or B cells to prevent them from

attacking, absent the appropriate signals.9

Cytokines. Researchers have found that the

cytokines — including such proteins as the interferons,

interleukins, and tumor necrosis factor (TNF), which

the body produces in response to viral and bacterial

infections — are critical in determining the outcome 

of an immune response. Researchers also have found

that cytokines differ between male and female mice 

and in female mice at different phases of their reproductive cycles. For example, one study found that the

immune response of pregnant mice differed from that

of nonpregnant mice, suggesting that shifts in cytokines strongly influence outcomes of infections 

during pregnancy.10

Antigen Processing. Researchers have found that

antigen processing, which enables the immune system 

to recognize infectious agents, is tied to the mechanisms that synthesize and recycle all proteins inside

cells and transport them between intracellular compartments. A major part of this new knowledge is the

understanding of how an enzymatic complex called 

the proteasome is involved in the transportation of the

peptides by the genes TAP (for Transporter associated

with Antigen Processing). The greater understanding of

antigen processing has helped clarify what is occurring

at a molecular level inside both diseased and healthy

cells and has aided in vaccine development.11
28

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Relationship Between Immune System and Neurological and Endocrine Systems. The discoveries of the many

relationships between the immune system and the 

neurological and endocrine systems has legitimatized

neuropsychoimmunology as a field of study. Estrogen

receptors have been located on macrophages and on 

a B-cell subset, allowing researchers for the first time 

to determine what is the direct effect of estrogen and

what is an effect mediated through a cellular cascade.

Estrogen-response elements have been located in genes

important in immune regulation, such as the gene

encoding of interferons. This knowledge will also

enable researchers to understand in detail how hormones work to activate or depress different pathways 

in the immune system. Researchers have found that

lymphoid cells also have receptors for neurotransmitters and even make some neurotransmitters, thus

allowing mental health and emotional states to affect 

the immune system.12

Clinical Intervention Advances

Many of the increases in basic knowledge in 

the past 5 years have already been translated into 

diagnostics and therapeutics.

Genetic and Other Markers of Human Disease. The

recent development of technologies for the identification of genes conferring susceptibility to a number of

diseases will permit clinicians to tailor therapy to particular diseases according to an individual’s prognosis.

For example, physicians can now identify individuals

with human lymphocyte antigens (HLA) haplotytes,

which predispose an individual to severe disease, and

can now identify serologic and cellular markers of diabetes in patients before they need insulin therapy.

Physicians are also beginning to test interventions 

that might prevent the full expression of diabetes. 

Transplantation. The understanding of the development of cells within the immune system has revolutionized the medical management of patients undergoing

chemotherapy and transplantation. For example, in

bone marrow transplantation, scientists are growing

small amounts of marrow cells in the laboratory so that

the patient can be given both stem cells and mature

cells, thus eliminating the period during which the

transplant recipient is at risk from infections.13

Treatment of Multiple Sclerosis. As a result of the 

better understanding of cytokine regulation of the

immune response, the treatment of multiple sclerosis

has been enhanced by the introduction of three new

drugs: Betaseron, Copaxone, and Avonex. (To date,

only Betaseron has been tested.)

Treatment of Osteoporosis. Big advances have been

made in the clinical intervention in bone metabolism,

which is useful in treating osteoporosis. Accelerated

osteoporosis is a major side effect of steroid therapy

used to treat many autoimmune and allergic conditions. A new class of drugs, phosphatose inhibitors, 

are now in clinical use to prevent bone resorption. 

In addition, estrogen replacement therapy is now 

routinely used to prevent osteoporosis. 

Treatment of Lupus. A clinical trial known as 

SELENA (Safety of Estrogen in Lupus Erythematosus

National Assessment) is now addressing questions

about the use of estrogen as an oral contraceptive and

estrogen replacement therapy in postmenopausal

women with lupus.14

Asthma. Recent research on the immunologic basis

of asthma, and the identification of the inciting antigens

in asthma, and other allergic conditions has enabled

the medical community to better treat asthma patients

and to develop strategies for desensitizing patients. 

Advances in Epidemiology/Natural History

Advances have also been made in understanding the epidemiology and natural history of many

immunologic diseases.

• The National Institute on Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has been

working with the Centers for Disease Control and

Prevention and the National Center for Health 
29

VOLUME 4

Statistics on a major paper updating information on all the major immune diseases 

and osteoarthritis.15

• Several studies have focused on whether ethnic 

differences affect natural history and outcome. 

For example, studies have shown how the genetic

risk factors for lupus differ for Caucasians, blacks,

and Hispanics and that socioeconomic variables

also constitute important risk factors.16 Also, 

a study of the HLA haplotypes predisposing 

Caucasians, blacks, and Hispanics to rheumatoid arthritis found that different haplotypes 

may associate with rheumatoid arthritis in 

different ethnic populations.

• The use of meta-analysis has facilitated the gathering of precise epidemiologic data. Meta-analysis 

is a method of summing the results of multiple

studies of a phenomenon, which increases the 

statistical power brought to bear on the research

question and thus greatly enhances the precision 

of estimates of effect. This approach has been

applied in studies on such diseases as lupus and

rheumatoid arthritis and on the use of estrogen 

and oral contraceptives.17

• Better tissue banks, blood banks, and other 

repositories have been developed to facilitate 

basic epidemiologic and clinical therapeutic

research. 

Advances in Behavior and Education

Physicians have learned the importance of 

empowering patients to take better control of their 

diseases, which results in more effective therapy. 

Various studies have shown that patients who see

themselves as having control over their lives have

diminished disease, compared with those who 

believe that they have no control.18

GAPS IN KNOWLEDGE

In spite of the tremendous advances that have

been made in the past 5 years, many gaps remain. 

Scientists are still unable to explain what causes the

autoimmune diseases, for example, or why these 

diseases predominantly strike women. 

Basic Science Gaps

Although gene-targeting technology has created

opportunities to manipulate the mammalian genome 

in ways that were unimaginable even a few years ago,

scientists still have a great deal to learn. Additional

studies are needed on risk factors and immunologically mediated tissue injury and on the role 

of environmental factors in immune responses.

With good definitions of a specific disease and 

of the population being studied, the powerful sib-pair

technology should yield a great deal of information

about which genes constitute risk factors in specific

populations. Sib-pair technology compares the genes 

of two siblings having the same disease with the genes 

of other siblings, relatives, and others to determine 

the specific genes involved in the disease. Similar

approaches will facilitate the understanding of the

mechanisms of immunologically mediated tissue 

injury, which would help researchers determine why

some autoreactivity leads to disease and some does 

not, and why it leads to disease in some people but 

not in others.

A major gap exists in knowledge about the role of

environmental factors in immune responses, whether

intercurrent infections, pollution, stress, or nutrition

are all separate issues. An advance has been that

researchers understand the legitimacy of these fields 

of investigation, but they know little about how 

environmental factors work.

More studies are needed of the various autoimmune diseases. After reviewing the medical literature

for incidence and prevalence rates of 25 autoimmune
30

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

diseases, researchers at Johns Hopkins University

found that epidemiologists have done little research 

on many of the autoimmune diseases. They found 

that although some autoimmune diseases had been frequently studied, such as multiple sclerosis (64 studies),

rheumatoid arthritis (21 studies), and systemic lupus

erythematosus (16 studies), many diseases had been

the subject of only two studies each (Addison’s disease,

polymyositis/dermatomyositis, Sjögren’s, uveitis, and

vitiligo), and others had been the subject of only one

study each (chronic active hepatitis, Graves/hyperthyroidism, and pernicious anemia), and some had never

been the subject of a study (autoimmune hemolytic

anemia, strep, pemphigus, and rheumatic heart disease). The researchers emphasized the urgent need for

further studies to increase scientific knowledge about

the prevalence and incidence of autoimmune disorders, 

in light of their medical and public health impact 

and of their cost to the U.S. health system.1

Gaps in Knowledge About Gender Differences

Although researchers now have some information

about how immune responses differ in women and

men and how they differ in women at different phases 

of their reproductive cycles, they still have much to

learn about gender differences.

• Researchers know little about whether gender 

differences lead to greater susceptibility to infection or to an altered response to vaccination. 

• Many times researchers find no statistically significant difference between women and men because

the standard deviation for women is far greater

than for men. The increased variability of the

immune response in women is a significant 

finding and should be pursued further. 

• Scientists know little about which differences

between males and females are sex-determined and

which are hormonally regulated, or which are the

result of other factors, such as body mass and body

weight. To a large extent, sex differences have been

assumed to be hormonally mediated differences.

Yet, one study found that the incidence of the

onset of diabetes in girls and boys was 3:1 before

puberty, and 2:1 after puberty. This finding indicates that the greater susceptibility of females to

diabetes is due to more than just sex hormones. 

• Most of the basic research has been done in

rodents, which have a different reproductive cycle

from that of humans. Consequently, issues of how

the menstrual system affects immune responses, 

for example, cannot be determined by a study 

of rodents. Nevertheless, the current availability 

of new laboratory mice allows researchers to begin

addressing the question of gender differences for

many immune functions. 

• Scientists still know little about how to apply basic

molecular knowledge to the treatment of women.

They do not know if therapies for women should

differ from those for men, if women’s therapies

should take into account the menstrual cycle, 

or if the therapies have different side effects in

women than they have in men.

• Studies are also needed on why some autoimmune

diseases, such as Reiter’s syndrome and ankylosing

spondylitis, are more common in men than in

women, to determine what the mechanisms are

that make men more susceptible and women 

less susceptible to those diseases. 

• Scientists are still unsure about whether cell 

signaling differs between men and women and

between those who are predisposed to certain 

diseases and those who are not predisposed.

• Few studies have focused on gender differences.

More studies are needed on such questions as 

the effect of the woman’s phase of development 

on her immune system. For example, clinical 

trials for estrogen studies seldom include women

who have never been pregnant, even though the

effect of pregnancy on the woman’s immune 

system is important.
31

VOLUME 4

• Although NIH requires that all data be analyzed 

by comparing genders, journals seldom publish

studies where no differences were found because

they consider this fact uninteresting. 

Clinical Intervention Gaps

Many of the recent advances in basic science have

yet to be translated into better diagnostic and therapeutic tools. Although one reason is that pharmaceutical

companies are sometimes little interested in many of

the immunologic diseases that affect women because 

of the relatively small market, the most important 

barrier is that scientists have yet to determine how 

to make the translation. The following are some of 

the major areas where translations to clinical interventions need to be made.

Apoptosis. With a better understanding of the

mechanisms of cell death through apoptosis, scientists

might develop the ability to push pathogenic cells into

an apoptotic pathway, which could result in better

treatments for such varied disorders as cancer and

rheumatoid arthritis.

Anergy. A better understanding of anergy could

prove useful in preventing the rejection of transplanted organs and for treating patients with 

autoimmune diseases. 

Mucosal Immunity. The new understanding of

mucosal immunity in the mouse could lead to a better

understanding of mucosal immunity in human beings 

so that therapies can be developed to excite immunity 

in a particular mucosal system (the eye, mouth, gut, 

or vagina), in order to combat various diseases, such 

as cervical cancer, or to make the immune system 

tolerate particular antigens, in order to combat 

diseases like multiple sclerosis. 

Antigen Processing. The benefits of the work on

antigen processing and presentation could eventually

result in better treatments for many illnesses, from

infections to cancer. The understanding of the existence of two types of antigens — agonist, which turn 

on immune responses, and antagonist, which turn off

immune responses — could lead to vaccines that will

turn on an antigen-specific response in an infectious

disease or block an antigen-specific response in an

autoimmune disease.

Gender-based Differences for New Therapies.

More clinical trials are needed to test new therapies for immunologic diseases, including analyses 

of whether the efficacy and side effects of these new

therapies differ in men and women. For example,

methatrexate for rheumatoid arthritis may pose no

threat to men but can cause cervical cancer in women.

Vaccines. Researchers are close to identifying 

protective epitopes or immunogenic epitopes in 

many infectious diseases. This information will help

researchers develop better vaccines and help them

determine how the effectiveness of vaccines varies 

with gender and with age and when is the best time 

for giving vaccines. In 1995, the Centers for Disease

Control and Prevention recommended flu immunization of pregnant women for the first time. However, 

no one knows whether the immunizations have 

different efficiencies in the various trimesters. 

Impact of Hormones and Life Changes. Studies are

needed on the effect of hormones on the different parts

of the immune system. In rat models, the antibodies 

in the vagina and uterus will have different responses

to the administration of hormones. This fact has lifethreatening implications for women trying to balance

fertility with protection against disease. The failure to

consider both of these concerns simultaneously is an

urgent issue in much of the world today. Systematic

studies are needed on how the changes associated 

with pregnancy, menarche, and menopause affect 

the outcomes of immunologic diseases or the impact 

of the use of oral contraceptives and hormone 

replacement therapy. 

Different Susceptibility to Autoreactivity. Researchers 

need to understand why the same immune response

can have different outcomes in different people. For
32

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

example, some people with kidney disease will have

anti-DNA antibodies, and some will not; some people

with thyroid disease will have anti-thyroid antibodies,

and some will not. Scientists need to understand 

more about what makes a target organ susceptible 

to immune injury. They also need to understand 

why outcomes differ in general, how they differ 

in men and women, and how they differ over the

woman’s life span.

Neuropsychoimmunology. A better understanding 

of how the manifestations of depression vary in men 

and women suffering from chronic diseases is fundamental to developing gender-sensitive immune 

therapies to prevent these manifestations. Also, the 

psychological and sociological aspects of immune 

disorders that occur disproportionately in women, 

such as fibromyalgia and the chronic fatigue 

syndrome, should be examined. 

Gaps in Epidemiology and Natural History

Two of the major gaps in epidemiology and natural

history are the lack of a comprehensive immunological

database and of multidisciplinary research. Although

the NIH Office of Rare Diseases is now setting up a

database for clinical trials, it will exclude the projects

being supported by private companies. Generating

improved databases would help researchers do more

informative research and more targeted clinical trials.

These databases might also provide the opportunity for

assessing the risk factors of rare diseases, such as lupus,

and of widespread diseases, such as osteoporosis. 

Many repositories exist — DNA repositories and

serum repositories, for example — that researchers

probably do not know about. For example, NIH has

given numerous grants that support databases that 

are theoretically open to researchers outside the 

institutions. Researchers need information on what 

databases have been created. Clinical researchers 

looking at a particular virus or bacteria that they 

think may play a part in the autoimmune disease

should have access to the findings of other 

researchers who are studying the same agent. 

More multidisciplinary research is also needed,

especially in light of the fact that infectious agents 

and toxins trigger certain autoimmune diseases. 

Closer collaborations should be fostered among 

immunologists, microbiologists, protein chemists, 

toxicologists, pathologists, epidemiologists, 

behavioral scientists, and clinicians. 

Gaps in Behavior and Education

Generalists need better training on when to refer

patients to a specialist in immunologic diseases. Too

often, doctors tell their patients with undiagnosed

autoimmune diseases that they are imagining their

symptoms. Many patients have to see four or five 

doctors before getting a correct diagnosis. This situation may be a factor in some women’s turning to 

alternative medicines and may be exacerbated if 

health care systems restrict access to specialists. 

Physicians also need to become aware of the

importance of a family history of immunologic disease.

At present, physicians will routinely ask about a family

history of cancer or high blood pressure, but they

rarely ask about a family history of immunologic 

disorders. Both the physicians and the general public

need to be made more aware that immunologic 

diseases tend to run in families. 

Public awareness of autoimmune diseases would

encourage people to offer information to their physicians, which might help the physicians detect the 

disease earlier than they otherwise might. However,

public information campaigns have been most effective when they are based on preventive measures that

people can take, for example, exercising or eating vegetables. At present, too little is known about the risk

factors of many autoimmune diseases to recommend

particular behaviors.
33

VOLUME 4

SPECIAL ISSUES

The participants in the Working Group on 

Immunology discussed their concerns about two special issues: (1) the underrepresentation of minority

populations in clinical studies of various diseases, 

and (2) the potential threat that the new managed 

care system poses to continued progress in 

immunologic research.

Minority Populations

• Women cannot be treated as one homogeneous

group. Disease and clinical intervention must 

be studied in all ethnic and racial groups. 

• One of the problems in dealing with minorities 

is that researchers are using social definitions 

to ask biological questions. Either the social 

definitions should be made more stringent, 

or researchers should find a way to correlate 

biological definitions with social definitions. 

• Classifying various ethnic and racial groups 

together as “Native American” or “Hispanic,” as

researchers often do, results in erroneous data. For

example, many studies have been based on data on

Mexican participants, the largest Hispanic population in the United States, and then extrapolated to

Hispanics from other countries, although vast differences exist among the various Hispanic groups. 

• Because of their different cultural and linguistic

backgrounds, Native Americans, Hispanics, and

other minority groups sometimes vary in their

interpretations of questions that researchers ask

them, which results in incorrect survey data.

Researchers should identify minority populations appropriately, tailoring their questions 

to specific ethnic groups. 

• One of the barriers to doing research on Native

American populations is that tribal groups often

require that researchers seek their permission to

work with the tribe, a process that sometimes takes

years. Another barrier is that many tribes regard

research with disfavor because in the past they

have felt exploited by researchers; however, this

attitude is changing as more Native Americans 

are being trained to do research. In general, it 

is important that researchers communicate well

with individuals of different ethnic and cultural

backgrounds in order to dispel any distrust of 

the research community that may exist.

Managed Care

The new managed care system could enhance

immunologic research in many ways. For example, 

the new system will likely generate larger, more centralized databases. As more data become available,

researchers may be able to determine whether a problem correlates more with a woman’s racial or ethnic

background or with her socioeconomic status. Finding such information is difficult today because study

participants are often uninsured, or the insurers are

unwilling to share the data. However, the new system

could also present some problems.

• Managed care companies may be unwilling to collect the type of information that public health care

professionals need, or they may be unaware of the

need for such information. For example, for a

study of mortality birthweight, it is not enough 

to know that the mothers are Hispanic; rather it 

is necessary to know whether they are Dominican,

Cuban, Mexican, and so on. The lack of detailed

information will limit researchers’ ability to eventually do clinical trials because managed care companies may be less willing to try new therapies.

• Physicians will have an incentive for overlooking

the possibility that a patient’s symptoms indicate

the presence of an immunologic disease, in order

to avoid referring the patient to a specialist. 
34

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

• Information on epidemiology and natural history,

or on which clinical interventions are effective 

and which are not, may become less accessible to

researchers because they will have limited access 

to patient populations. Researchers should remind

NIH and the U.S. Department of Health and

Human Services that these are issues that need to 

be considered as major issues as the new health

management system is established. The public

health function may not be funded in the new role

of managed care; there may be no set-aside for

these kinds of surveillance and research activities. 

• Managed care companies often do not allow

patients to participate in clinical trials. 

• Managed care may pose a special problem for

immunologic diseases in terms of the training 

of physicians. The limited access to patients and

consequent limited remuneration may discourage

people from specializing in rheumatology, allergy,

and other immunologic diseases. Women physicians, especially, will find it harder to compete in 

the new managed care environment because the

concern about the bottom line will discourage

companies from allowing women the flexibility

they have had in the past 10 years to combine

career and family.

• A recent study by the National Institute of Arthritis

and Musculoskeletal and Skin Diseases of the

potential outcomes for patients with chronic 

diseases, rheumatoid arthritis, and lupus in 

the managed care environment found that the

patients requiring care with chronic diseases 

tend to be poor, do badly, and should do 

even worse in a managed care system.19

RESEARCH 

RECOMMENDATIONS

The Working Group on Immunology made 

the following recommendations to improve 

future research: 

• More studies of immune modulation and response,

target organs, cell signaling, and other basic phenomena should be conducted. Until researchers

have more basic knowledge in these areas, they

will be unable to translate their knowledge into

clinical interventions. 

• Gender-based differences should be fully explored 

in immunologic functioning. Researchers should

analyze their data by gender, unless scientifically

justified not to do so.

• The effect of the hormonal environment, as 

defined by puberty, pregnancy, and menopause,

should be carefully examined.

• The role of external pressures, including the 

environment, in immunologic diseases should 

be studied.

• The investigation of mucosal immunity should be

expanded in order to provide a better understanding of the body’s tolerance of orally administered

antigens in the treatment of various diseases. 

• Researchers should try to translate the animalbased data they have in some meaningful way 

to human beings. 

• More multidisciplinary research should be done. 

• NIH should establish a central source of information about the many databases that exist — patient

registries, cell banks, DNA banks, serum banks,

and brain banks. NIH should work with such local
35

VOLUME 4

organizations as local chapters of the Lupus Foundation, Arthritis Foundation, Multiple Sclerosis

Society, and Office of Crohn’s Disease in establishing this comprehensive database. Also, researchers

should be trained to get informed consent for the

use of their samples for later research projects.

They should also be instructed on the proper

preservation of their samples. 

• Steps should be taken to ensure that an adequate

number of immunologists will be trained under 

the new managed care system, with special emphasis on encouraging the training of women 

in clinical and basic immunology. 

• Better education should be provided to the general physician and to the public on the diagnosis

and treatment of immunologic diseases. 

References

1 Jacobson, D.L., Gange, S.J., Rose, N.R., Graham, N.M.

September 1997. Epidemiology and estimated population

burden of selected autoimmune diseases in the United

States. Clini Immunol Immunopathol 84(3):223–43.

2 Capecchi, M.E. March 1994. Targeted gene replacement.

Sci Am 270 (3):52–59.

3 Theophiloupulos, A.N. 1995. The basis of autoimmunity:

Part I: Mechanisms of aberrant self-recognition; Part II:

Genetic predisposition. Immunol Today 16:90–98;

150–158.

4 Zinkernagel, R.M., Doherty, P.C. 1997. Major transplantation antigens, viruses, and specificity of surveillance 

T cells. Contemp Topics Immunobiol 7:179–220.

5 Weiner, H.L. July 1997. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol

Today 18(7):335–43.

6 Lou, Y.H., McElveen, M.F., Garza, K.M., Tung, K.S. May

1996. Rapid induction of autoantibodies by endogenous

ovarian antigens and activated T cells: implication in

autoimmune disease pathogenesis and B cell tolerance. 

J Immunol 156(9):3535–40.

7 Springer, T.A. 1995. Traffic signals on endothelium for

lymphocyte recirculation and leukocyte emigration. 

Annu Rev Physiol 57:827–72.

8 Qian, D., Weiss, A. April 1997. T-cell antigen receptor

signal transduction. Curr Opinion Cell Biol 9(2):205–212.

9 Schwartz, R.H. August 1993. T Cell anergy. Sci

Am:62–71; Schwartz, R.H. Immunologic tolerance. In

Fundamental Immunology, ed. W.E. Paul, third edition,

Raven Press.

10 Mossman, T.R., Sad, S. March 1996. The expanding 

universe of T-cell subsets: Th1, Th2, and more. 

Immunol Today 17(3):138–46.

11 Engelhard, V.E. August 1994. How cells process 

antigens. Sci Am:54–61.

12 National Institutes of Health. 1995. Mind-body 

interactions and disease. Health Dateline Press.

13 Brugger, W., Heinfeld, S., Berenson, R.J., Mertelsmann,

R., Kanz, L. August 1995. Reconstitution of Hematopoiesis after high-dose chemotherapy by autologous

progenitor cells generated ex vivo. New Engl J Med

333(5):283–87.

14 Office of Research on Women’s Health. 1996. Final 

Report of the Office of Research on Women’s Health: Fiscal

Years 1993–1995. Bethesda, MD: National Institutes 

of Health, p. 21.

15 Lawrence, R., Helmick, C., Arnett, F., et al. Prevalence 

estimates of arthritis and selected musculoskeletal 

disorders in the United States. Arthritis and 

Rheumatism, in press.

16 Salmon, J.E., Millard, S., Schacter, L.A., Arnett, F.C., 

Ginzler, E.M., et al. March 1996. Fe gamma RIIA alleles

are heritable risk factors for lupus nephritis in African

Americans. J Clin Invest 97(5):1348–54.

17 Felson, D.T., Anderson, J.J., Meenan, R.F. October 1994.

The efficacy and toxicity of combination therapy in

rheumatoid arthritis. A meta-analysis. Arthritis Rheumat

37(10):1487–91.

18 Karlson, E., Daltroy, H., Lew, R., et al. January 1997. The

relationship of socioeconomic status, race, and modifiable risk factors to outcomes in patients with systemic

lupus erythematosus. Arthritis Rheumat 40(1):47–56.

19 Institute of Medicine. 1996. Changing Health Care Systems

and Rheumatic Disease. National Academy Press.

Infectious Diseases and

Emerging Infections

BACKGROUND

The startling advances since 1991 in the detection and treatment of infectious diseases inwomen help indicate what still needs to be

accomplished. The 1991 Hunt Valley report grouped

together research recommendations in immunology

and infectious diseases. The current report recognizes

the growing importance of both these areas and treats

their discussion and research recommendations in 

separate sections.

It was not possible for this working group to 

cover all infectious diseases of particular importance 

to women. Time was, of course, a consideration; 

however, the expertise of the working group, as well 

as evidence of the increasing scope of the epidemics, 

led to a focus on sexually transmitted diseases (STDs)

and HIV/AIDS, with limited discussion of a significant

number of other infectious diseases. For instance, 

the group did not discuss urologic diseases of women

because none of the group’s members were experts 

in this area. Therefore, the four sections that follow 

will focus on STDs and HIV, with passing references 

to other infectious diseases from which women suffer

disproportionately. Discussion within each section of

this report is divided into basic science, epidemiology,

clinical practice, and behavior and education.

Sexually transmitted diseases, including HIV/AIDS,

require a continued concentrated research effort. Many

of the STDs are more difficult to detect in women than

in men, and in many ways, these diseases affect women

more severely. As a consequence of STDs, women may

experience infertility, tubal pregnancy, genital cancer,

early fetal loss, and congenital or perinatal infection.

Efforts should be continued to reveal more about the

microbial and behavioral etiology of these infections;

their differential effects on women across the life span;

measures women can take to prevent contracting them

or prevent their progression to later stages; and the

effects of these diseases on the communities and subcommunities in which women live.

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT

OF ORWH

Advances in Basic Science

Basic research progress in the fields of HIV and

STDs in the past 5 years is evidenced in the many new

studies being undertaken and in the significant increase

over the past several years in research funding. The

ambitious research and program agendas of the National

Institutes of Health and the Centers for Disease Control

and Prevention have included an increase in funding

by the National Institute of Allergy and Infectious Diseases of STD centers that are focusing on an examination

of the vaginal ecosystem. Other projects have begun to

characterize the endogenous defense systems of the

vagina and cervix. Grant-funded research is currently

focusing on vaginal immunology and physiology, and 

Cochairs

Sharilyn K. Stanley, M.D.

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Howard Minkoff, M.D.

SUNY Health Science Center at Brooklyn

Rapporteur: Donna R. Savage

37

VOLUME 4
38

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

is examining normal and abnormal vaginal ecosystem

responses to preventive and therapeutic agents. Examples of basic scientific progress include the development of single-dose azithromycin for treatment of

chlamydia and research on mucosal factors in 

relation to STDs.

The medical literature has reported new advances 

in basic science research on HIV/AIDS. For example,

the recent findings of the AIDS Clinical Trial Group

076 showed that in pregnant women with HIV, antepartum and intrapartum zidovudine (AZT) treatment 

of the mother, followed by short-term treatment of the

baby, reduced the risk of vertical transmission of HIV

infection from approximately 24 to 8 percent. New

antiviral drugs have been studied and approved for

treatment of HIV-infected persons, including protease

inhibitors, which are an entirely new class of antiviral

drugs. People who elect antiviral therapy can now take 

a combination regimen that results in sustained suppression of virus production, increased CD4 cell

counts, and improved quality of life. Specifically with

regard to women’s health, recent advances in basic

research on HIV include, in addition to the focus on

perinatal transmission of the virus, research on the 

natural history of the virus and its disease progression 

in women. The case definition for AIDS in women 

has been expanded to include new diagnostic criteria

for HIV-positive persons (including invasive cervical

cancer); this has resulted in improved identification 

of previously unsuspected HIV infection in women.

Epidemiologic Advances

Epidemiologic research has highlighted both the

extent of the STD epidemic in the United States and its

consequences. For example, a major finding in recent

years is the demonstration of a causal relationship

between human papilloma virus (HPV) and cervical

cancer; so strong is that causal relationship that cervical

cancer can now be considered an STD. With the advent

of urine-based testing and regulations to obligate STD

reporting, epidemiologists revised the estimates of the

magnitude of chlamydia infections in the United States;

whereas the estimate of American women infected

annually had been around 4 million, that figure 

is now 8 to 10 million infections per year. The 

estimates for Americans infected with genital herpes 

and HPV are 43 and 40 million, respectively. In addition, scientists are beginning to identify individuals

who are either nonprogressors or are resistant to 

STDs despite exposure or infection.

One of the biggest steps forward in understanding the epidemiology of STDs and HIV is the finding 

that the diagnosis and the treatment of STD decreases

the risk of HIV transmission. One study has demonstrated that the treatment of persons with STDs 

resulted in a significant reduction in the incidence 

of HIV infections in the treated population. In 

addition, routine screening for asymptomatic 

chlamydia has proven efficacious in reducing 

the incidence of pelvic inflammatory disease.

Natural history studies of HIV in women have

helped determine how HIV is acquired and the appropriate clinical utility and prognostic significance of viral

load and CD4 counts. The gynecologic manifestations

of HIV are also being defined. More accurate and more

timely diagnoses of HIV in women have resulted from

the broadening of the case definition for AIDS, which

includes increasing the range of symptoms that defines

the presence of HIV in women, as well as the increasing recognition by clinicians that women are at risk 

for HIV infection. The risk factors for heterosexual

transmission of HIV are now better defined.

Advances in Clinical Practice

Clinical and therapeutic triumphs in the past 5

years are evident in the availability of new diagnostic

tests and new drugs, including antiretrovirals (especially protease inhibitors). The findings of the AIDS

Clinical Trial Group 076 showed that when AZT was

given to pregnant women during pregnancy and delivery, and to infants in the first 6 weeks of life, the risk of

vertical transmission of HIV was reduced substantially

(25.5 percent to 8.3 percent). Single-dose therapies,
39

VOLUME 4

such as azithromycin for treatment of chlamydia, show

great promise in large part because ongoing patient

compliance is not required. Better diagnostic methods

have been developed, such as polymerase chain reaction (PCR) and liquid chain reaction techniques using

urine-based (and therefore noninvasive) sampling for

the diagnosis of chlamydia infection; multiplex PCR 

for congenital ulcer disease; and home-based tests for

HIV. Other clinical progress includes earlier diagnosis

of infections such as chlamydia and HIV that allows 

the prevention of complications of disease, and the

development of the second-generation hepatitis B 

vaccine and the improved acellular pertussis vaccine.

Advances in Behavior and Education

Epidemiologic data have helped to describe 

the occurrences and transmission of STDs and have

helped bring about an increased sensitivity to the

importance of behavior as an area that should be 

studied and addressed. For example, documentation 

of the increasing numbers of women diagnosed with

HIV has led to growing awareness that the HIV epidemic is not limited to the homosexual male population. This awareness has prompted more diverse 

educational messages about HIV, resulting in significantly increased awareness that women may be at 

risk for HIV infection; with counseling, voluntary 

testing for HIV infection has increased. In some settings, condom use has increased substantially; the 

Thailand prostitute study indicated that consistent condom use can substantially reduce STD transmission.

Advances in Scientific Perspective

What has begun to underlie the scientific progress

described above is progress in the conceptual perspective about research on women’s health. No longer is 

the vagina viewed, in research terms, merely as a 

repository for semen and a vessel for fetal and/or

microbial growth, but rather as a complex ecosystem

that should be studied in this context in order to

advance biomedical knowledge about the infectious 

diseases that afflict women.

GAPS IN KNOWLEDGE

Gaps in Basic Science

The consensus about the importance of a research

focus on the vagina as an ecosystem brings to light a

myriad of gaps in basic science: general knowledge

about the vaginal ecosystem, interactions of the vaginal

ecology with multiple exogenous substances (topical

microbicides, sperm, and douching), effective topical

microbicides that are not necessarily spermicidal, and

vaginal microbiology across the woman’s life span. Gaps

in prevention and diagnosis include the lack of an

effective procedure for diagnosing syphilis at certain

stages, understanding the role of STDs in adverse outcomes of pregnancy, the lack of an effective vaccine for

most STDs, and the unavailability of rational advice 

to offer on the management of human papilloma virus

infection. The need for useful animal models, identified

in the 1991 Hunt Valley Report, still exists. Other gaps

include understanding what happens once an organism

invades the host and how the host controls or eliminates the infection; adverse neonatal outcomes related

to maternal STDs, including why herpes-infected newborns develop a wide range of different symptoms; 

and the pathogenesis of infertility and tubal scarring,

including why some women recover reproductive 

ability after pelvic inflammatory disease whereas 

others do not.

Gaps in basic science knowledge of HIV infection

range from understanding the precise mechanisms 

of transmission to delineating the pathogenesis of 

full-blown AIDS in women. Gaps in knowledge about

transmission and initial infection include how to quantitate the infectious viral load in genital secretions; how

infection is established (what is the first cell that gets

infected?); the in vivo role of peptides that inactivate

HIV and other organisms and viruses in test tubes; 

and the effectiveness of natural defense mechanisms

such as pH level and the presence of lacto-bacilli. Gaps

in knowledge about HIV, pregnancy, and hormones

include the role of the placenta as a viral barrier, since
40

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

75 percent of infants born to an infected mother are

not themselves infected; whether pregnancy increases

susceptibility to HIV infection; the role of HIV in

adverse outcomes of pregnancy; hormonal influences 

on viral expression; and the safety of antiretroviral drug

treatment during pregnancy. Additional gaps include

the biologic interaction of STDs and HIV, particularly

with regard to effects on the regulation of HIV expression, oral markers for HIV infection, vaginal yeast

infections as early markers, and HIV strain differences

regarding susceptibility to and progression of infection.

Epidemiologic Gaps

Gaps in epidemiologic knowledge of STDs and

HIV include the need to re-address what should be

reportable as an STD and the legal and ethical barriers 

to reporting. Barriers exist to enrolling women in natural history studies, especially in the use of consent

forms and conforming to study guidelines. Research is

sorely lacking on women in underserved communities,

such as correctional facilities, where rates of STD and

HIV infection are very high. There is a paucity of data

on STDs in sexually abused children and adults. Longterm epidemiologic studies on STDs are needed; for

example, research is needed to evaluate the long-term

outcome in babies who were given AZT for 6 weeks

after birth to prevent HIV vertical transmission from

the mothers.

Structural methods are needed to design community-based studies and to evaluate these data in a

manner that leads to valid conclusions. These studies

would focus on risk factors that occur on a communitywide level, including sociocultural factors.

Additional research is needed to better define the

transmission and epidemiology of herpes simplex virus;

to determine the optimal timing for administration of

the hepatitis B virus vaccine and how long its protective effect will persist; to understand chlamydial disease

progression and the development of complications; to

describe the natural history of T. vag. infection in men as

asymptomatic transmitters to women; to define, using

population-based studies, the role of lacto-bacillus and

other normal vaginal flora in preventing infection; and

a better understanding of the findings of previous surveys that indicate that gonorrhea, syphilis, and HIV

infection all overlap within the same population. Research is also needed to understand the natural history

of human papilloma virus. Epidemiologic studies

focusing on the serotypes of HIV and the relationship 

of these serotypes to mechanisms of HIV transmission

and course of disease are needed. Finally, more powerful microbiologic tools are needed to facilitate epidemiologic research.

Gaps in Clinical Practice

Despite progress since the 1991 Hunt Valley

Report, women are still not being sufficiently enrolled in

clinical trials. This is true particularly for underserved

women such as substance abusers or women who are

incarcerated. In some prisons, women are screened for

infectious diseases and are isolated if infected, while in

other prisons this does not occur. For a variety of reasons, women who are incarcerated or who are drug

abusers also do not have access to the latest treatments

for infectious diseases. The failure to screen and treat

incarcerated women not only presents a health concern

inside prison walls but also creates a serious public

health issue in the community, since most of the incarcerated women will return to the general population.

Clinical practice still does not have available inexpensive, rapid, noninvasive, reliable diagnostic methods

and vaccines for all viral STDs, including HIV. Other

clinical concerns include the increasing development 

of microbial resistance to therapies, the diagnosis and

treatment of tertiary syphilis, methods for the complete

elimination of chlamydia infection and subsequent prevention of tubal scarring, and the development of singledose therapies for infections other than chlamydia. In

addition, significant gaps exist in our understanding 

of the acceptance of, compliance with, and optimal

immunologic time and techniques for STD vaccination protocols; the immunologic consequences of 

such vaccines are also not currently understood.
41

VOLUME 4

Two additional factors may have contributed to 

the continued gaps in the laboratory diagnosis of STDs.

First, the well-intentioned requirement of the CDCissued Clinical Laboratory Improvement Act (CLIA) —

mandates that clinics that routinely perform STD tests

obtain special certification — may have had the unexpected result of a decline in laboratory testing for

STDs. Second, the emergence of managed care will

almost certainly impact STD screening and may result

in a decrease in prevention and screening. An emphasis

on the cost effectiveness of prevention and screening

over the treatment of established infection will be 

necessary to avoid a reduction in the availability 

and utilization of these services.

More information is needed about the effects 

of therapy for STDs and HIV on pregnancy. Finally, 

optimal methods for the prevention of perinatal 

infections remain an area for further investigation.

Gaps in Behavior and Education

Fundamental knowledge and research are lacking

on the conduct of patients and health care providers.

For instance, given that messages from physicians have

been shown to make a behavioral difference, we still 

do not understand how to successfully motivate

providers to discuss behavior with their patients.

Knowledge about sexual behaviors is also inadequate, particularly with regard to adolescent behavior.

The complex issues surrounding choices about reproductive health are not understood. For example, what

are the behavioral outcomes related to the competing

choices of birth control versus STD control? How can

women effectively negotiate for safer sex and for riskreducing behavior in their steady or casual consorts?

CHANGE IN QUESTIONS

SINCE HUNT VALLEY

The working group felt that, in the 5 years since

the Hunt Valley Report, a conceptual paradigm shift

has occurred regarding research on women’s health.

Because society and the health professions are now 

less likely to view women as mere reproductive beings,

the concept of “women’s health” has expanded beyond

reproductive health issues; serious attention is being

paid to the great variety of morbidity and mortality

health issues affecting women.

The female genital tract is not simply a “receptacle”

and conduit of infection or reproduction, but rather 

an ecological system not yet well understood. Complex

and multiple events occur in the vaginal ecosystem,

leading to questions such as “What does it mean to

study the vagina?” and “How does what happens in 

the vagina affect the whole woman?”

To direct and develop the research questions and

recommendations, the working group identified three

crosscutting themes: emphasis on prevention; recognition of the changing parameters throughout the

woman’s life span; and understanding the continuum 

of health issues that ranges from the individual to the

community. These themes are defined below and

should be applied as a filter for all recommendations 

for research on women’s health.

• Emphasize prevention. Research should focus on 

a continuum of prevention methods to avoid 

infections and their complications:

– primary: prevention of infection;

– secondary: prevention of disease; and

– tertiary: prevention of disease complications.

• Consider the changing context throughout women’s life

cycles. Research on women’s health should take into

account the full biological life cycle of the woman

and the concomitant physical, mental, and emotional changes that occur. Easily identifiable stages 

in a woman’s life are childhood, puberty, age of

reproduction, and menopause. For example,

research should elucidate the impact of the given

life stage of the individual on the progression of

infectious disease from exposure to asymptomatic

carriage to full-blown disease. In addition, there

may be significant differences in the acceptance
42

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

and efficacy of vaccines and therapy due to 

the effects of hormonal variations that occur

throughout the menstrual cycle.

• Address the full continuum from the health of the 

individual to the health of the community. Research

studies should be undertaken that will affect not

only an individual woman’s health but also the

health of her family and the communities within

which the woman lives and works. Different infectious diseases impact certain communities to varying degrees; the reasons for this, and the influence 

of community on the diagnosis and treatment 

of the individual, must be better understood.

RESEARCH 

RECOMMENDATIONS

Basic Science

The Vagina. STD research should focus on the

human vagina. Research is needed to increase knowledge about the vaginal ecosystem: the “normal” state,

alterations caused or enhanced by exogenous factors;

effects of the menstrual cycle on disease; effects of the

frequency of intercourse, both with single and with

multiple partners, on disease; and changes in the 

vaginal ecosystem across the life span.

Primary Prevention Tools. Research should focus 

on the effectiveness of exogenous hormones, topical

microbicides, barrier methods, and vaccines as primary

prevention of STDs, including HIV. The development

of nonspermicidal microbicides is necessary for women

who want to prevent infectious disease but not necessarily pregnancy. An important public perception for

researchers to consider is that, when the individual

feels protected against pregnancy and/or against one

STD because of the use of a barrier method, they also

incorrectly feel protected against all STDs. For example, a condom does not protect the individual from

contracting chlamydia or human papilloma virus; 

nevertheless, the public perceives condoms as protection against all STDs. This must be considered 

in STD primary prevention research. 

Pathogenesis of STDs. Research on the pathogenesis

of STDs should focus on the requirements for microbial

growth, survival, and reproduction, and on environmental factors that enhance microbial growth; on 

determining whether genetic predispositions render 

certain hosts more or less susceptible to microbes; 

and on how the status of the host’s immune system

affects microbial growth and reproduction. Thus,

research must address microbial, host-genetic, and 

host-immunologic factors. Research to investigate 

the interactions within the host between STDs and 

HIV is needed.

Basic Pathogenesis of HIV. Research to elucidate 

the pathogenesis of HIV/AIDS in women should be 

continued and include the study of the influences 

of hormonal and other natural defenses on viral 

expression, the local vaginal factors that affect 

susceptibility and disease progression, and 

mechanisms of vertical transmission. 

Therapeutics for Adverse Outcomes of Pregnancy.

Continue and increase research to prevent the myriad 

of adverse outcomes of pregnancy caused by STDs 

and HIV. Conduct research on infertility, its causes, 

and methods to reverse it.

Hormonal Birth Control Methods. A systematic

research agenda is needed for the study of the potential effects of hormonal birth control methods on a

woman’s susceptibility to infection. Such research must

include girls and women across a wide range of reproductive ages. A safe, female-controlled contraceptive

method that would be effective in preventing pregnancy and the transmission of STDs, including HIV,

should be developed. In this regard, studies are 

needed on the efficacy of the female condom for 

contraception and prevention of STDs.

Animal or Other Reproductive Models for Effective

Study of STDs. While important, the development 

of animal models should not be undertaken at the

expense of research devoted to women. Caveats of

using animal models include the substantial differences between the mechanisms of action of hormones
43

VOLUME 4

and microbes in humans versus other species, and 

the differences in frequency of sexual contact and 

number of sexual partners.

Epidemiology

Followup Studies. Followup studies should be 

conducted to determine the long-term sequelae 

of vaccines, treatments, and disease progression. 

For example, babies who were given AZT in utero 

and during their first 6 weeks of life to prevent 

vertical transmission of HIV are being followed, 

with particular emphasis on identifying potential 

late adverse effects of AZT. A few additional longterm epidemiologic studies exist for HIV, but very 

few exist for other STDs. Gonorrhea, syphilis, 

and HIV overlap significantly in some populations; followup studies should be done with 

these populations as well.

Community-based Studies. Risk behavior and 

risk factors for STDs, including HIV, that occur 

on a community-wide level need to be identified.

Methods to design community interventions and 

evaluate the resulting data can then be developed.

Link Between Race and Disease. Conduct research 

to determine whether a relationship exists between

race-based factors and specific infectious diseases. 

For example, gonorrhea is 60 times more prevalent 

in African Americans than in whites; this could result

from several different factors, such as genetic susceptibility or community behaviors. Understanding the

reasons is essential to the development of effective 

prevention and treatment. Factors that may be 

implicated in disease progression and infection 

include genetic, environmental, socioeconomic, 

and sociocultural factors.

Access to Underserved Groups. Research should 

be conducted on populations with high rates of 

infectious diseases, which have typically been understudied or underaccessed. For example, STD/HIV 

rates in prisons are very high, and epidemiologic

research on this population is sorely lacking.

Natural History of T. Vag. in Men. Conduct research

to determine the role of men as reservoirs for T. vag. and

as asymptomatic transmitters of the disease to women.

HIV Serotypes. Conduct epidemiologic studies to

provide data on the effect of HIV serotypes on HIV

transmission and development of disease. Delineate 

the factors that contribute to differences in virulence 

as well as differences in regional transmission of 

certain serotypes.

Microbiologic Tools. Develop microbiologic 

tools to facilitate epidemiologic research. 

Clinical Practice

Product Development. The phrase “diagnose everything easily and cure everything simply” sums up the

long-term recommendation for product development.

New diagnostic methods and treatments should be

inexpensive, rapid acting, as noninvasive as possible,

reliable, accurate, and easy to use; product research

should make these characteristics a priority.

Clinical Trials. Enroll more women in efficacy and

safety trials. This recommendation has two implications: (1) conduct more clinical trials on women’s

health issues, and (2) enroll more women in clinical 

trials in which men have previously prevailed in numbers. Specifically, clinical trials on microbicides and

other barrier methods are needed to define the efficacy, the safety, and the long-term sequelae of STD 

and HIV therapy not only on the “typical” patient 

but also on pregnancy and neonatal outcome.

Researchers will need access to clinical trials and 

treatment for women with HIV and women who are

pregnant; both groups have often been excluded from

studies in the past. In addition, studies should be 

conducted on patients with multiple infections.

Cures and Vaccines. Continue research to find 

cures for viral STDs and HIV, to develop methods to

combat microbial resistance, and to develop treatments and vaccines to prevent or eradicate these 

infections entirely. Train dental personnel to recognize oral lesions as a sign of HIV infection.
44

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Public Health Policy Research. Evaluate ways to

reduce the negative consequences of changes in public

health policies (e.g., the Clinical Laboratory Improvement Act). Begin to think about how to implement

nationwide vaccine-delivery programs, patterned 

perhaps on the delivery of the measles vaccine, so 

that the medical establishment is prepared for the

upcoming completion of the herpes simplex vaccine as the first in what will hopefully be a series 

of vaccines for STDs.

Prevention and Treatment for Underserved Women.

Study the consequences of inadequate comprehensive prevention and therapy for STDs/HIV in prisons.

Study the impact of needle exchange programs on 

the spread of HIV.

Behavior and Education

Behavioral Methodologies and Measurement.

Conduct behavioral science research on both 

patients and health care providers. For behavioral 

theories that already exist, determine if they are 

being validated and used effectively to alter behavior. 

For new theories that may be formulated, provide 

access for utilization and validation in the field.

Sexual Behaviors, Especially of Adolescents. Develop 

a catalog of sexual behaviors as a base for any intervention strategy. This recommendation underpins

many of the other research recommendations in this

report. The development of effective vaccines, cures,

and prevention messages relies on an understanding 

of sexual behavior across the life span and within 

and across communities.

Subject Participation and Compliance. Conduct

research on how to increase recruitment and retention 

in clinical trials and how to enhance compliance with

treatment regimens. If treatment compliance research

results in only a 10-percent increase in compliance,

this will indicate a substantial need for improvement 

in screening, prenatal care, vaccinations, condom use,

microbicide use, and other prevention methods. There

should be a focus on pregnant women and women

who use illegal drugs, since compliance issues are 

often of particular concern within these groups.

Effects of Public Health Messages and Societal Norms

on Behavior. Information is necessary, but not sufficient,

for behavior change. Research is needed to determine

not only what information should be disseminated but

also how information is delivered. For example, most

people know that HIV is fatal, but this information

often does not change risk-taking behaviors. Public

health messages must be evaluated with the understanding that societal beliefs and social norms are

essential components of behavior change. Evaluation 

of public health campaigns should consider the behavioral outcomes of the competing choices women must

make; for instance, a choice to prevent STDs but not

necessarily to prevent pregnancy. Research on the

impact of popular culture and societal norms on 

individual and group behavior change is crucial.

Other Research Recommendations

In addition to STDs and HIV, many other women’s

health issues related to infectious diseases should

receive research attention in the next 5 years. The

working group did not have the time or the expertise 

to deal with these issues in depth but believed they

should be addressed in this report. These issues

include the following:

• Urinary tract infections. Morbidity associated with

urinary tract infections encompasses such problems as “honeymoon cystitis” and incontinence.

• Tuberculosis. After adolescence, a woman’s risk 

of disease progression after exposure to tuberculosis is significantly higher than a man’s risk. 

An understanding of the factors contributing to 

this increased susceptibility to disease, such as 

hormones, pregnancy, contraceptives, or lifestyle, 

is needed.
45

VOLUME 4

• Chlamydia and heart disease. More women die 

from heart disease than from breast cancer. With

recent findings that chlamydia may be involved 

in atherosclerotic lesions, this relationship in

women must be evaluated.

• Chronic fatigue syndrome. Investigators are currently searching for an infectious disease cause 

for chronic fatigue syndrome, a condition that

affects women twice as often as men. Further

research into the pathophysiology of this condition is warranted.

• Malaria. Initial research indicates that pregnancy

increases the death rate from malaria and that 

the disease has an affinity for certain placental 

cells. More research is needed on this re-emerging infectious disease.

• Group B Strep. This infection is the number one

cause of neonatal septicemia. With additional

research, particularly vaccine development, 

this disease could be diagnosed, treated, 

and eliminated.

Other infectious disease issues for women’s 

health research include bacterial vaginosis and other

nonsexually transmitted vaginal diseases, hepatitis C,

H. pylori, infectious etiologies of rheumatoid diseases,

toxic shock syndrome, and the long-term immunologic sequelae of rubella vaccinations.

Emerging Infections. Emerging infections are infections that either have newly appeared, appeared in

species previously unaffected, or are rapidly increasing 

in incidence or geographic range. Recent examples

include outbreaks of plague in Surat and India and the

Ebola virus infection in Zaire. Most emerging infections

are not caused by genuinely new pathogens. Shifting

ecological, environmental, and demographic factors

precipitate the emergence of disease either by placing nonimmune people in increased contact with a

pathogen or its natural host in its native environment,

or by promoting dissemination into new regions or

new hosts. The current volume, speed, and reach of

international travel make emerging infections a significant global problem. The working group made specific

note of the importance of cooperative research and

information sharing with other countries.

RECOMMENDATION 

FOR DEVELOPING 

A FULL AGENDA

The working group recommends that a 2-day

retreat be arranged to delve more fully into the 

diseases listed. Infectious diseases are critical health

issues for women, and a longer period of time is 

needed to develop a full agenda for women’s health

research in infectious diseases.

HIV

• David Ho’s Viral Dynamics;

• Rosenthal, “Changing Face of the HIV Epidemic” 

in a 1995 edition of Science;

• Monthly statistics from the MMWRs;

• Quinn, on the global HIV epidemic, in Lancet;

• Scott Holmberg (from CDC) in the American 

Journal of Public Health, on calculating HIV 

infection rates in 58 metropolitan centers; and

• Jeff Kelly article (from Penny Hitchcock) on 

what has worked in HIV prevention.

HPV

• Ho and Burke, “Natural History of HPV,” 

in Cancer; and

• Pulaski articles.

Herpes

• Brown, Natural History and Pregnancy; and

• Use of PCR for diagnosis.

Mental and Addictive

Disorders

BACKGROUND

Although mental and addictive disorders were

not formal topics for discussion at the 1991

Hunt Valley conference, many recent findings

indicate body and mind cannot be separated. Inclusion

and equal status at the “Beyond Hunt Valley” symposia

is a significant change that represents progress for these

areas of research, placing mental and addictive disorders on a par with physical disorders. The integration

of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse

(NIDA), and the National Institute of Mental Health

(NIMH) into the National Institutes of Health (NIH)

has given national impetus for mental and addictive

disorders, represented by these institutes, to be placed

on a par with physical diseases, disorders, and conditions. While mental and addictive disorders were

included on the list of priorities of the Office of

Research on Women’s Health (ORWH) from its inception, the integration of the Institutes supporting

research on these important women’s health concerns

ensures systematic attention to these disorders.

The biological and sociological roles of gender

have been recognized as powerful factors in the causes, 

correlates, and treatment of mental and addictive disorders. With new awareness about how the differences

between men and women affect wellness, it is critical

to present, study, evaluate, and implement changes

based on gender-based research to positively impact

the treatment of mental health and addictions in

women. Concerns about mental and addictive disorders must be addressed on a multi-tiered level; 

clinicians and researchers must be willing and able 

to work even more closely together to promote wellness in mental health for women in the 21st century.

Mental Disorders

Taken as a group, mental disorders affect both

sexes with equal frequency; however, important gender

differences exist in the prevalence, symptoms, and

treatment responses of specific disorders. For example,

major depression and dysthymia (a less severe, more

chronic form of depression) affect approximately twice

as many women as men. An estimated 21 percent of

U.S. women experience a major depression during

their lifetime, compared with 12.7 percent of men; 

and additional 8 percent of women have dysthymia.

Women are two to three times more likely to have 

anxiety, panic, and phobic disorders. The eating disorders anorexia nervosa and bulimia nervosa affect

women at an eight to ten times greater frequency then 

in men. While schizophrenia and manic-depressive 

illness are equally prevalent among men and women,

they also appear to be marked by gender differences 

in age of onset, pattern of symptoms, treatment

response, and natural course.

Mental disorders in women are inextricably linked

to their own physical health and to the health and well

being of their families. Because women are often care

givers for their parents and children concurrently, a

Cochairs

Delores L. Parron, Ph.D.

National Institute of Mental Health 

Elizabeth Young, M.D.

Mental Health Research Institute

47

VOLUME 4
48

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

woman’s mental disorder may affect two or three generations. Conversely, the burdens of women’s multiple

responsibilities often create stresses that can amplify

mental disorders.

Simply studying a group termed “women” is not

enough. Multiple variables, in addition to gender, affect

research and treatment: age, physical health, stage of

menses, ethnicity and race, marital status, parental status, education, income, occupation, sexual orientation,

labor force participation, and geographic location;

other differences exist in accessibility of services, and

administration of services. Furthermore, study groups

that often are not identified by gender, such as studies

on children and animals, need to be recorded and analyzed by gender in the future in order to understand

the biological processes and developmental course 

of gender-related risk and protective factors.

Addictive Disorders

Alcohol Abuse. Alcohol remains the drug of 

choice among Americans today. According to the 

1992 National Longitudinal Alcohol Epidemiological

Survey (NLAES) one-third of women age 18 and older

are current drinkers, 21 percent are former drinkers,

and nearly 4 million women (4.1 percent) were found 

to be alcohol abusers or alcohol dependent according 

to Diagnostic and Statistical Manual, Fourth Edition

(DSM-IV) criteria.

Fewer women than men drink alcohol, and

women who drink consume less alcohol and have

fewer alcohol-related problems and dependence symptoms than men. However, among the heavier drinkers,

women equal or surpass men in the number of problems that result from their drinking. Studies of alcoholdependent women in treatment suggest that they often

experience greater physiological impairment earlier in

their drinking careers, despite having consumed less

alcohol than men. The interval between onset of drinking-related problems and entry into treatment appears

to be shorter for women than for men. Women become

intoxicated after drinking smaller quantities of alcohol than are required to produce intoxication in men.

Female alcoholics have premature death rates 50 to 100

percent higher than those of male alcoholics. Women

develop alcoholic liver disease, heart muscle damage

(alcoholic cardiomyopathy), and brain damage with

lower daily alcohol intake and at an earlier time in 

their drinking careers. Proportionately, more alcoholic

women die from cirrhosis than do alcoholic men.

Drug Abuse. The 1994 National Household Survey

on Drug Abuse indicates that females comprise 45 percent of those who reported ever using illicit drugs in

their lifetime, and 37 percent of individuals reporting

use in the prior month. The survey also found that

more women than men reported having taken prescription drugs for nonmedical purposes during the past

month. The National Pregnancy and Health Survey,

conducted by the National Institute on Drug Abuse,

reported that in 1992, among women who gave birth

in the United States, an estimated 221,000 used illicit

drugs while they were pregnant. The National Comorbidity Survey, conducted between 1990 and 1992, estimated that 6 percent of all women 15 to 54 years of age

have met the criteria for lifetime drug dependence.

Women frequently have predisposing psychiatric

disorders prior to their drug abuse. Research on antecedents of crack cocaine abuse has found pre-existing

psychiatric problems, particularly depression, to be a

major co-factor. Additionally, drug-abusing women

have been reported to have conflicting relationships

with, and less attachment to, their mothers. Women

who have been victims of crime, also, appear to have

increased vulnerability to substance abuse.

A high correlation exists between eating disorders

and substance abuse. Moreover, research indicates that

the more severely a woman diets and engages in binge

eating the more likely she is to meet the criteria for

substance abuse or dependencies and the more likely

she is to experience negative consequences from 

drinking alcohol and using drugs.
49

VOLUME 4

Women present a unique set of physical, social,

and psychological problems that require specific interventions to meet their needs. Many women at risk 

for drug use/abuse have low self esteem, are single

mothers (often with limited parenting skills), come

from minority communities, are often school dropouts

and therefore have few marketable job skills, and have

had at least one sexually transmitted disease. Women

look to men for protection and support but, unfortunately, many of those men are themselves involved 

in drugs and influence the woman to become drug

involved also.

There is growing evidence that the effects of drug

abuse and addiction do not always affect men and

women in the same manner. For example, data indicate

that for illicit drugs, women may proceed more rapidly

to drug dependence than do men. There is also evidence that nicotine dependence in females, relative to

males, is controlled less by the nicotine itself and more

by psychosocial factors, including the use of cigarettes

as a “nicotine delivery system” for use in weight loss.

One of the most devastating consequences of drug

use for females is the risk of HIV/AIDS. AIDS is now

the fourth leading cause of death among women 15 

to 44 years of age. In the United States, over 78,000

cumulative cases of AIDS were reported in women and

female adolescents by mid-1996 and 64 percent of the

AIDS cases among women are related to injection drug

use. Injection drug use and heterosexual sex with an

injecting drug user (IDU) play a major role in AIDS for

women. Seventy to 80 percent of AIDS cases ascribed

to heterosexual contact in the United States have been 

in women, most of them in young women who use

crack cocaine and who trade sex for money or more

drugs. Forty-six percent of AIDS cases in women are

attributed to injection drug use and 18 percent to 

heterosexual contacts with IDUs; in comparison, 22

percent of AIDS cases in men are related to injection

drug use, and one percent to heterosexual contacts

with IDUs. Additionally, among the total cases of 

pediatric AIDS in the United States, 54 percent are

related either to the mother’s injection drug use 

or to the mother having had sex with an IDU.

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT

OF ORWH

Recommendations from 1991 Hunt Valley Report

In the 1991 Hunt Valley Report, the Working

Group on Mental and Addictive Disorders recommended attention to the following:

• Comorbidity among mental illness, substance 

use, and physical illness — the identification of

certain subgroups of women at risk (genetically, 

by psychosocial history, chronic stress) for comorbid illness could prove useful for preventive 

treatment efforts.

• Genetic and environmental factors contributing 

to mental and addictive disorders through genetic

epidemiology — in order to develop promising

prevention strategies.

• Significant gender differences in prevalence of

mood, anxiety, and personality disorder.

• Biological and psychosocial gender-related variables related to the development, onset, course,

treatment, and relapse of mental and addictive 

disorder, including early developmental history 

— the role of sexual and physical abuse.

• Gender differences in cognitive and/or personality

variables that may influence onset or recurrence 

of disorders.

• Psychological and biological factors linked to 

gender in suicide attempts and completions 

across the life span.

• Gender differences in grief reactions and depression following bereavement.

• Gender differences in the development of phobic

avoidance for social and specific phobias and 

agoraphobia.

• More refined behavioral and pharmacologic 

interventions for alcohol and substance use 
50

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

disorders that consider issues unique to women,

including demands of caregiving for children 

and other family members.

Progress in the 5 years since the establishment 

of ORWH includes the following:

Mental Disorders in Women — Progress

The latest data from epidemiological studies continue to show that depression, anxiety disorders, and

eating disorders affect women more often than men.

While some progress has been made in the search for

the causes of this gender-based disparity, investigators

are generating novel hypotheses that are now propelling research forward. For example, preliminary data

raises the possibility that estrogen’s interactions with

the circadian pacemaker may somehow be involved in

seasonal affective disorder and rapid-cycling bipolar

disorder, illnesses that affect women more than men.

There is much to learn about mental disorders by

studying gender differences in the biology, behavior,

epidemiology, and treatment of these illnesses. The 

past decade has seen research flourish along these lines,

and out of that effort has come a new understanding 

of the burden that mental disorders place on women.

Research targeted specifically on women’s mental 

health problems, including those resulting from violence, is necessary to help women reach their full

potential — and society to reap the benefits of 

healthy women’s full participation.

Research on gender differences in mental 

illnesses is shedding light on the roles and interactions of biological and environmental factors 

in the following disorders.

Depression and Related Disorders. Out of the recent

wealth of mental health related clinical and epidemiological data, gender emerges strongly and consistently

as a major risk factor for depression, with depressive

disorders affecting more than twice as many women as

men. Yet despite the robustness of this finding, much

less is known about specific etiologic factors that

underlie this association. Further complexity stems

from the reality that the mood disorders represent 

a broad spectrum ranging from those that arise primarily in reaction to environmental stressors to those

related more strongly to endogenous factors. The role

and relative weight of various gender-specific factors

may differ across this spectrum, and may also influence symptom patterns, comorbidity, course, 

treatment response, and outcome.

Community and clinical samples have indicated

that gender-specific risk for mood disorders varies with

the specific type of mood subtype. Men and women

differ little in rates of bipolar disorder, but have been

shown to vary strikingly in the broader spectrum of

unipolar disorders. Nonetheless, there is evidence that

men and women with bipolar disorder may differ in

clinically significant ways in phenomenology, comorbidity, and course. Recent research indicates that the

course of bipolar illness in women is characterized by

more depressive and fewer manic episodes, and that

women are more likely to develop the rapid-cycling

form of the illness. Gender differences in prevalence are

more pronounced in unipolar depressive illness, with

some early evidence that differences may be greater in

the less severe forms. Clinical studies have found that

women predominate in seasonal affective and rapid

cycling bipolar disorders and in dysphoric mania.

The differential actions and beliefs of socializing

agents — parents and teachers holding different expectations and behavioral norms for boys and girls —

combined with the impact of differences in how boys

and girls construct gender identities may cause girls,

more than boys, to exhibit high levels of self-evaluative concerns that increase their later vulnerability 

to depression. Gender stereotypes and socialization

processes may lead males and females to feel differently

about themselves and to attach different importance 

to meeting evaluative standards imposed by parents,

teachers, and other people important in a child’s life.
51

VOLUME 4

An NIMH-funded longitudinal study of social

development in young children found evidence supporting the idea that girls (but not boys) as young as

age 4 have lower scores on measures of perceived competence, self confidence, and self esteem, and have

more negative feelings following failure, and that these

correlated with higher scores (more depressed feelings)

on the Children’s Depression Inventory. Scores on the

depression inventory move toward normal as the girls

move through the first 4 years of school, suggesting

that girls are more vulnerable during periods of transition — entering school and entering puberty — than

during times of stability. If future longitudinal research

finds that these observations are reliable developmental

markers, then it may be possible to take steps to help

at-risk girls and women through transition periods and

thus reduce their vulnerability for depression.

Anxiety Disorders and Posttraumatic Stress Disorders.

Phobias, a type of anxiety disorder, are extremely common in the general population. Two to three times as

many women as men are affected by phobias, making

research on these disorders a particularly important

issue for women’s mental health. Data suggest that 

even simple phobias predispose to more serious 

anxiety and depressive disorder in late life.

Posttraumatic stress disorder (PTSD) is an anxiety

disorder first characterized in male combat veterans,

but soon was found also to affect female victims of

trauma. Core symptoms of PTSD include:

• experiencing a distressing event that involved 

actual or threatened death or serious injury, 

or a threat to one’s physical integrity, and that

involved intense fear, helplessness, or horror;

• re-experiencing the trauma in nightmares, 

intrusive thoughts, or flashbacks;

• numbing of responsiveness or avoidance of

thoughts or acts related to the trauma; and

• symptoms of dysphoria and arousal.

Although many forms of intervention exist for

rape-related PTSD symptoms, only a few well-controlled studies have been conducted to systematically

evaluate the treatment response of women who have

been the victims of sexual assault. Overall, cognitivebehavioral interventions for rape-related PTSD, with

single or multiple treatment components, have been

found to produce a decrease or remission of posttrauma

problems when compared to no treatment. Cognitive

desensitization, in which the victim practices relaxation

techniques in a safe environment while mentally reliving the trauma, weakens the fear response triggered 

by these terrible memories. Few women receive such

therapy, however, since the most common professional

intervention for rape victims is the limited crisis intervention counseling offered in rape crisis centers. Recent

data show, however, that such limited therapy is not

enough to help many women overcome PTSD following sexual assault, suggesting that the nation’s rape

counseling network can be significantly enhanced.

Studies of women victims of violent crimes have

shown that cognitive-behavioral interventions can

reduce posttrauma problems that plague these women

and help them escape the fear-induced anxiety that can

limit their daily activities. Unfortunately, few women

receive such therapy, pointing out the need to increase

outreach and educational efforts aimed at women and

women’s health centers.

Eating Disorders. The eating disorders anorexia 

nervosa and bulimia are primarily seen in women. 

People with anorexia starve themselves into extreme

weight loss, a behavior that is associated with an irrational fear of becoming obese and severe body-image

disturbance of near psychotic proportions. Those 

with bulimia engage in repeated binge-eating episodes

followed by self-induced vomiting, fasting, or using

laxatives or diuretics. It is not uncommon for the 

two disorders to occur together.

It is well established that individuals with bulimia

recover more often than do those with anorexia or 
52

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

both disorders. However, a recent NIMH-funded 

survey of women with anorexia found that nearly half

the anorexic and mixed subjects no longer met full

diagnostic criteria for at least 8 consecutive weeks 

during the first year after completing psychotherapy 

for the disorder. Total recovery at 1 year — no 

symptoms of the disorder — was seen in 56 percent 

of bulimia patients, compared to 18 percent of women

with both anorexia and bulimia and 10 percent of

women with anorexia alone. It is not known how 

many of these “recovered” patients stay symptom 

free beyond 1 year, suggesting that a long-term 

monitoring effort is needed to gain a better understanding of the prognosis for these disorders.

Though little is known about the central nervous

system mechanisms involved in these eating disorders,

researchers are focusing currently on cholecystokinin

(CCK), a neuroactive peptide that exists in high concentration in the gut and in regions of the brain associated

with satiety. Measurements of CCK in the cerebrospinal

fluid of women diagnosed with bulimia and in healthy

volunteers found that bulimia sufferers had significantly

lower levels of this peptide.

Mental Health and AIDS

Issues of mental health and behavior arise at every

point in the progression of AIDS — from the risk-taking behavior that contributes to transmission of HIV, 

to the early signs of HIV entry into the central nervous

system, to the psychological, social, and behavioral

challenges faced by all HIV-infected individuals and

their friends and families, to the devastating late-stage

dementia that affects many AIDS patients, and ultimately to the profound loss and bereavement suffered 

by those left behind.

Recent accomplishments of basic and behavioral

research related to mental health and HIV/AIDS

include:

• Successful behavioral interventions developed to

address the risk factors of specific groups with

increasing rates of HIV transmission, including

women and people with severe mental illness.

• Methods refined for the early detection of cognitive

impairment in people infected with HIV who have

no other medical symptoms.

• Scientific understanding of the biochemical events

that take place in the brain and central nervous

system during various stages of HIV infection.

• Animal models developed that permit closer 

investigation of different aspects of HIV infection 

of the central nervous system.

Research on the pathogenesis of HIV infection will 

ultimately lead to better ways to treat — and possibly

prevent — the cognitive and motor impairments

caused by HIV/AIDS.

Addictive Disorders in Women: 

Alcohol Dependence — Progress

At least three factors have been found to account 

for differential susceptibility of women to alcohol. 

First, women have less total body water than men of

comparable height and weight. After ingestion, alcohol

diffuses uniformly into all body water, both intra- and

extracellular. Because of their smaller amount of body

water, women achieve higher blood alcohol concentrations (BAC) than men after consuming identical

amounts of alcohol. Second, research indicates that

diminished activity of gastric alcohol dehydrogenase

(ADH) in women may contribute to the gender-related

differences in BAC as well as heightened vulnerability

to the physiological consequences of drinking among

women. First-pass metabolism (when alcohol is metabolized in the stomach by gastric ADH) decreases the

availability of alcohol to the body. Due to decreased

activity of gastric ADH, first-pass metabolism is

decreased in women relative to men, and is virtually

nonexistent in alcoholic women. Third, fluctuations 

in gonadal hormone levels during the menstrual cycle

may affect the rate of alcohol metabolism, according 

to recent studies, making women more susceptible 

to elevated BACs at different points in the cycle.

The relationship between alcohol consumption

and bone density/calcium metabolism is a complicated
53

VOLUME 4

one. Male alcoholics are known to be at markedly

increased risk for osteoporosis; however, in postmenopausal women, low levels of alcohol consumption

appear to contribute to increased bone density. Now 

a recent study raises questions about the long-term

health consequences of drinking even a small amount

of alcohol while taking estrogen replacement therapy.

The study found that when postmenopausal women 

on oral estrogen therapy drank half a drink, the levels

of estrogen circulating in their blood nearly doubled.

After three drinks, estrogen levels tripled. Recently,

many large epidemiologic studies have indicated that

alcohol consumption, even at levels as low as one to

three drinks per week, is associated with a moderately

increased risk of breast cancer. Since alcohol consumption has been shown to elevate estrogen levels, this is 

a possible mechanism for causing breast cancer.

Recent treatment research indicates that women 

do as well as men in top-quality alcoholism treatment.

However, more research is needed to determine if outcomes for women in treatment can be optimized by

using gender-specific modalities.

Addictive Disorders in Women: 

Drug Abuse — Progress

Animal studies have shown that fundamental gender differences may exist in the reinforcing and stimulus properties of abused drugs. On several measures 

of stimulant-induced activity, females exhibit more

responsiveness than males; moreover, this responsiveness varies with the estrus cycle. Gender differences

have also been reported in self-administration of

cocaine. When cocaine infusions were made contingent upon an increasingly higher number of bar 

presses, female rats made substantially more presses 

than males and their level of cocaine self-administration varied as a function of the estrus cycle.

In human studies, the progression or developmental stages of drug involvement appear to differ

according to gender. In the progression from legal 

drug use to illicit drug use, for example, cigarettes

seem to play a major role for girls; for boys, alcohol

alone is sufficient. Women’s initiation into drug use 

also differs from that of men. A study on gender differences in cocaine initiation and abuse indicated that

approximately 90 percent of women reported that 

men played some role in their involvement with crack

cocaine; by contrast, only 17 percent of men reported

that women were involved in their initiating or maintaining the use of crack cocaine. Women were more

likely to begin or maintain cocaine use in order to

develop more intimate relationships, while men were

more likely to use the drug with male friends and in

relation to the drug trade. Since current unisex drug

abuse prevention efforts may be neglecting the primary

issues of females, the necessity of a female-specific 

program needs further investigating.

Childhood sexual abuse has been associated with

drug abuse in women in several studies. For example, 

a study of women in drug abuse treatment found that

70 percent of the women reported histories of physical

and sexual abuse, with victimization beginning before

11 years of age and continuing on a serial basis. Additionally, a risk-reduction study found that 74 percent 

of the women interviewed reported sexual or physical

abuse at some time in their lives (childhood, adolescence, or adulthood) and that 15 percent were abused 

at all three periods in their life. Women who were physically or sexually abused as adults reported engaging

in more drug use than women who had not been

abused in adulthood. Although, there is a growing 

literature on violence against women and its relationship to substance abuse, the path by which substance

abuse develops following childhood sexual abuse experiences in women is unclear. Further research is needed

to understand the etiology of this strong correlational

finding and address its implications for prevention 

and treatment efforts for women.

Women who abuse drugs may be more vulnerable to crime victimization than men. A recent study 

of homicide in New York City found that 59 percent 

of white women and 72 percent of African-American

women had been using cocaine prior to their death,

compared with 38 percent of white men and 44 
54

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

percent of African-American men. Although cocaine 

is used by more men than women, this study suggests

that its use is a far greater risk factor for victimization

for women than for men. In another study, conducted

among a population of women in residential or outpatient drug treatment programs, 80 percent had been

crime victims. Female crime victims were more likely

to have major drug and alcohol problems than nonvictims, and female crime victims who suffered from

PTSD were almost ten times more likely to have major 

alcohol problems and 17 times more likely to have

major drug abuse problems than nonvictims. Numerous studies have shown PTSD to be a strong predictor 

of substance abuse.

The long history of making pregnant women the

exclusive focus of drug abuse has shifted; the focus is

now on all females, regardless of their age or reproductive status. This new focus applies to all areas of drug

abuse research from determining women’s vulnerability

to substance abuse to determining specific treatments

for women. Researchers are also beginning to examine

drug effects affected by the menstrual cycle, including

the possible need to time cessation with a woman’s

body rhythms. Other studies are examining the hormonal status of the subject, acknowledging that the

presence of estrogen, for example, affects response.

There is general acknowledgment that, due to a

variety of barriers, female drug abusers have difficulty

accessing treatment and successfully completing a

course of treatment. Barriers have been identified in

treatment entry, engagement in treatment, and longterm recovery. Examples of such barriers have been

shown to be:

• lack of economic resources, referral networks, 

and woman-oriented services;

• conflicting child-related responsibilities;

• models of drug treatment that are primarily 

male oriented; and 

• lack of treatment modalities that address the 

specific treatment needs of women.

In past research on drug abuse, human and animal

subjects have been almost exclusively male; as a result,

little data has been available on women. Recently, however, gender differences have gained attention in the

field of drug abuse research, and preliminary data indicate that the biological mechanisms involved in drug

abuse and dependence vary considerably between men

and women. For example, a study examining gender

and menstrual cycle difference in response to acute

intranasal cocaine reported that mean peak cocaine

plasma levels in women were higher in the follicular

phase than in the luteal. This study also found that,

overall, male subjects achieved the highest mean peak

plasma cocaine levels, detected cocaine effects significantly faster than females, and experienced a greater

number of episodes of euphoria.

Studies on Comorbid and Addictive Disorders

Studies of comorbid psychiatric disorders in opiate

and cocaine abusers have reported findings consistent

with the epidemiology of these disorders in the general

population, specifically, a higher percentage of affective

and anxiety disorders in women than in men. The rate

of co-occurring substance abuse disorder and PTSD is

relatively high for women. Data from a study on female

crime victims, for example, indicate that women suffering from PTSD were 17 times more likely to have

major drug abuse problems than nonvictims. Furthermore, it has been shown that individuals with a trauma

history and PTSD symptoms use substance abuse inpatient services more frequently than do their non-PTSD

counterparts. This has led researchers to speculate that

the co-occurrence of substance abuse and PTSD often

predict a more severe course than would ordinarily 

be present with either disorder alone.

Additionally, a high correlation appears to exist

between eating disorders and substance abuse. For

example, recent research reported that as many as 

55 percent of bulimic patients have drug and alcohol 

use problems. Conversely, 15 to 40 percent of females

with drug abuse or alcohol problems were reported 

to have eating disorder syndromes, usually involving

binge eating.
55

VOLUME 4

OPPORTUNITIES TO

ADVANCE KNOWLEDGE

Research Across the Life Span

Gender differences in age of onset, and in 

age-related differences in the course of mental and

addictive disorders, suggest the need for both basic 

and applied research related to women’s mental and

addictive disorders across the life span. Attention to

differences in developmental trajectories within biological and psychosocial contexts is necessary in research

that considers either gender differences in mental and

addictive disorder or variation among females. There 

is a need to study postmenopausal women from their

70s through their 90s to find out why women in this 

age group often are more resilient than men.

Ethnic Minority Females

Knowledge about ethnic minority women’s mental

health and use of addictive substances is limited in

terms of understanding the etiology and prevalence,

the clinical course, intervention effectiveness, and service use related to these disorders. The meaning of ethnic identity as it pertains to acculturation, social class,

and sex-role socialization requires careful refinement

when considering associations with psychopathology.

Differences in response to high blood pressure medications among men of different ethnic groups suggest

that there may be possible differences in the pharmacokinetics and pharmacodynamics of psychotherapeutic

drugs among ethnic groups of women. Outreach to

ethnic communities is needed in order to fashion

research that addresses these concerns.

Impact of Violence

Overwhelmingly, women are the more likely 

victims of violent abuse. A study of a representative

national sample of women indicated almost 13 percent 

of women (about 12 million) have been raped and 11

percent more have been the target of aggravated assault 

at least once. Evidence indicates that there is more

drug abuse among women with a history of child

abuse. There is a possible association between a history

of sexual trauma and chronic gastrointestinal symptoms. Long-term studies are necessary to determine the

psychological and biological consequences of sexual

assault and other abuses. It is critical that the factors

involved in the relationship between drug abuse and

physical and sexual victimization (including partner

violence) be identified and understood.

HIV/AIDS in Women

Women’s unique HIV transmission contexts and

behaviors, including the link between drug dependence

and risky sex and the potential for vertical transmission,

have implications for the development of targeted, 

gender-specific risk reduction interventions, including 

programs for pregnant women. The following provide

direction for future gender-specific, HIV/AIDS-related

intervention research:

• An obvious gender difference is biological, with

HIV-infected women having the potential to transmit the virus to their infants. Pregnancy and childbearing (and childrearing) also create experiential

differences between men and women and may

have the effect of isolating women from participation in HIV risk-reduction interventions.

• Other experiential differences between men and

women include interpersonal power differentials

and the experience of physical or emotional violence. Being in an abusive relationship may negatively affect a woman’s ability to adopt protective

behaviors such as using condoms. Studies show

that women with abusive partners practice more

HIV-risk behaviors than nonabused women and 

are less likely to seek drug treatment, or disclose

their HIV status to their partners.

• Economic strategies are sometimes different

between men and women. Studies show that 

drug- dependent women are more likely men 

to engage in sex trade, raising the risk of HIV 

infection (women are also more likely to engage 

in other high-risk sex practices).
56

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

• Men and women sometimes have differential 

access to other resources, such as a greater 

number of drug treatment slots available 

for men than women.

• Cultural norms and gender-based role expectations

may affect women’s HIV risks relative to men’s; for

example, a recent study of IDU networks shows

that in multiperson drug injection scenes, men

were more likely to start an injection sequence 

and women were more likely to use a needle 

that had been previously used by someone else.

• Differences in psychosocial development may 

result in different communication styles for 

men and women and their interpretations 

of HIV risk-reduction messages.

Gender Differences in Pharmacology

Epidemiologic surveys indicate that women comprise 45 percent of those who report having used an

illicit drug in their lifetime, they are prescribed and use

psychotropic medication at twice the rate of men, yet

large gaps remain in the knowledge base of gender differences in pharmacology. Historically, this difference 

is due, in part, to the exclusion of women of childbearing age from drug-development trials because of fear 

of unintended birth defects. In addition, men have

been considered less complicated research participants

because their levels of sex hormones were assumed to

remain relatively constant, thus reducing the chance of

confounding results. By excluding women, researchers

have not had to concern themselves with questions

about the effects of the menstrual cycle, or whether 

the women were pre-, peri-, or postmenopausal or 

on hormone medications. This research strategy has

not furthered the understanding of gender differences

in pharmacokinetics and pharmacodynamics of psychotherapeutic drugs. Research should be undertaken 

to study the effects of psychotropic drugs and hormones over time, because millions of women take 

antidepressant drugs and hormone replacement 

medications regularly.

Drug Abuse

In addition to the above issues related to drug

abuse, studies are also needed to examine:

• the nature and extent of drug abuse in females 

of all ages, ethnic backgrounds, SES groups, 

and sexual orientations;

• the role of the menstrual cycle in modulating 

drug use and drug effects;

• gender-specific behavioral, biological, and 

medical effects of drug abuse; and

• gender-specific biological and behavioral mechanisms that underlie drug abuse and addiction.

Prevention research should be expanded to include

interventions based on female-specific antecedents,

pathways, and risk and protective factors.

Gender-focused drug abuse research is needed to

study the role of dieting and eating disorders in drug

abuse etiology, the relationship between affective and

anxiety disorders and drug abuse, and the role of PTSD

as a risk factor in drug abuse. Additionally, genderbased research is needed to examine the factors that

result in over-prescription and abuse of psychotherapeutic agents.

The development of well-designed, theoretically

based drug treatment models that address female-specific issues is necessary if treatment is to be effective.

The models should be broad based and comprehensive;

include pharmacological, psychotherapeutic, behavioral, and psychosocial treatment modalities; and

address co-existing psychiatric disorders (especially

depression, anxiety, PTSD, and eating disorders). These

models must also address service needs including child

care, transportation, assertiveness training, and vocational training. Such services, by themselves, do not

constitute treatment. However, if they are not provided,

women are likely to experience barriers to accessing

treatment and/or to remaining drug free. Within the

context of treatment, there is also a need to examine,
57

VOLUME 4

from the perspective of gender, the complex issues

involved in relapse.

Longitudinal studies from childhood through adulthood should be aimed at investigating gender differences

in the nature and extent of drug-using behaviors; gender differences in the pathways and determinants of

initiation, progression, and maintenance of drug use;

and gender differences in the basic behavioral mechanisms underlying drug dependence, vulnerability, and

protective factors need to be studied.

Alcohol Dependence

Research is currently lacking on:

• gender differences in alcohol metabolism;

• differential susceptibility of women to alcoholic

organ damage;

• effects of alcohol consumption on bone density 

and osteoporosis;

• long-term consequences of alcohol use while 

on estrogen replacement therapy;

• the relationship between alcohol use and breast

cancer; and 

• determination of optimal treatment methodologies

for women alcoholics.

Integration of Mental and Addictive Disorders into

Primary Care and Community Settings

The primary care setting presents an ideal opportunity for screening for mental and addictive disorders.

This opportunity is lost, however, if clinicians are either

not adequately trained or, because of the stigma attached

to these disorders and difficulties associated with reimbursement, are unwilling to address them. Primary care

clinicians are uniquely positioned to screen, diagnose,

treat, and refer. Their ability and willingness to provide

the full range of services is essential if mental and

addictive disorders are to be integrated throughout 

the health care delivery system.

Research Environment

Research is not user friendly to the average person,

in part because patient and researcher often do not

speak the same “language.” The actual service setting 

is an important variable: a person’s comfort level determines whether she will return, will be honest, or will

benefit optimally from care. The community could be

an important source of information to aid treatment;

therefore, outreach to the community, religious institutions, and into the home should be considered

important adjuncts to treatment regimens.

CHANGE IN QUESTIONS

SINCE HUNT VALLEY

In addition to the questions that fine-tune the

focus on studies of disorders most prevalent in women,

there are now questions that address variation among

women. Learning more about the roles of ethnicity, age,

sexual orientation, genetically and biologically based

variation, and social and economic resources in the 

etiology, course, and outcomes of mental and addictive

disorders among women will lead to more effective

treatment efforts. Examples of new questions include:

• What are the roles of specific (e.g., pregnancy,

divorce) and chronic stressors (e.g., single parenthood, caring for a dependent family member)

across the life span with regard to risk and course 

of mental and addictive disorders? What factors

compound the stressors to produce greater risks

(e.g., genotype, limited social and financial

resources), and what factors can protect against 

negative effects of these stressors?

• Less severe symptoms may cause as much, if not

more, impairment across the population due to

great prevalence as more severe clinical disorders

among fewer people. This may be particularly the

case for minor depression, with women assumed to

have higher rates than men. What is the prevalence

of minor depression? What is its functional impact

on work and relationships? And what are some
58

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

promising clues to prevention and treatment of

minor depression among both women and men?

• How does variation in a women’s physiological

response to drugs, possibly due to menstrual 

cycle or estrogen medication, affect treatment

approaches to both mental disorders (e.g., dosing

antidepressants) and interventions aimed at substance use (e.g., nicotine addiction)?

• What are the factors that contribute to more userfriendly preventive approaches for women at risk

for mental or addictive disorders, and similarly,

more user-friendly intervention strategies for

women already suffering from these disorders?

• What are the best treatment approaches to address

the more common comorbid disorders, such as

depression and nicotine addiction, depression 

and anxiety, or PTSD and depression, for certain

subgroups of women?

RESEARCH 

RECOMMENDATIONS

Summary Recommendations

Mental and Addictive Disorders Across the Life Span.

Encourage research on the interactions among biological, psychological, and social factors related to mental

and addictive disorders across the life span of women.

Predisposition to Mood, Eating, and Anxiety Disorders.

Encourage research to identify the social, developmental, and biological factors that predispose adolescent

girls and young women to a sharp increase in rates 

of mood, eating, and anxiety disorders.

Gender Differences in Brain Function. Stimulate

research on gender differences in brain function, 

specifically the effect of gonadal hormones on the

developing brain and their relationship to the formation of sexually dimorphic brain structures and

processes and how these distinctions could be related 

to gender differences observed in persons affected 

by mental and addictive disorders.

Neuroactive Peptides in Women with Bulimia. Further

explore the findings that levels of neuroactive peptides,

such as cholecystokinin (CCK), may be altered in

women with bulimia and that lower levels of this peptide also correlate with higher scores on measures of

anxiety and anger. Attempt to link these findings with

studies showing that CCK interacts with serotonergic

neurons, which have been implicated in the etiology 

of bulimia.

Long-term Effects of Violence and Victimization.

Encourage and support research on (1) psychological

and biological effects of sexual assault in childhood,

and (2) intervention research designed to prevent

and/or treat the long-term mental health effects 

of experiencing abuse and violence.

Gender Differences in Etiology and Consequences.

Conduct basic research (both human and animal) as

well as epidemiological and longitudinal research

directed at identifying gender differences in the etiology

and consequences of drug use, abuse, and addiction.

Antecedents, Pathways, Risk Factors, and Protective

Factors. Conduct research on antecedents, pathways,

risk factors, and protective factors involved in drug

abuse by girls and women, with emphasis on early

identification and the full spectrum of prevention 

interventions.

Co-existence with Mental Disorders. Conduct

research on the co-existence of drug dependence 

with psychiatric disorders, especially depression, 

PTSD, anxiety disorders, and eating disorders.

Drug Abuse Treatment Models. Expand research

examining the development and effectiveness of drug

abuse treatment models that are specific to the unique

needs of women. Such models should include treatment

for addiction as well as any co-existing psychiatric disorder (e.g., depression, anxiety, PTSD, eating disorders).

These models must also be culturally relevant.

Women and Alcohol. More research is needed to:
59

VOLUME 4

• Ascertain mechanisms of gender differences 

in alcohol metabolism;

• Determine the causes and mechanisms of differential susceptibility of women to alcohol 

organ damage;

• Explain and quantify the relationship between 

alcohol consumption and bone density and 

osteoporosis;

• Examine the long-term consequences of consuming

alcohol while on estrogen replacement therapy;

• Determine if the relationship between alcohol 

consumption and breast cancer is causal and, 

if so, by what mechanisms(s); and

• Determine optimal treatment methodologies 

for women alcoholics.

Address Diversity in All Research Studies. Many measurement tools used today were normed on white male

reference groups. These tools need to be re-examined

and validated for use with female and diverse ethnic

groups. Similarly, there is need for female-centered

models of treatment. In developing these models,

researchers need to be cognizant of the variables

important in women’s mental health, including racial,

religious, socioeconomic status, and sexual orientation.

Integrate Cross-disciplinary Research from Molecular

Level Through Societal Level. Mental disorders and drug

abuse are complex problems that involve mutually

interactive biological, behavioral, and societal factors.

Research is needed that integrates across these levels 

of analysis in order to understand this complexity 

and provide comprehensive solutions. Given that

researchers typically receive training in only one 

of these levels, cross-disciplinary collaborations are

needed to develop more integrated programs of

research. Prime topical areas for such cross-disciplinary collaborations in women’s mental health and

addiction include, AIDS/HIV, abuse, posttraumatic

stress disorder, and depression.

ACKNOWLEDGMENTS

This report was prepared with the assistance of

Mary Dufour (NIAAA); Adele Roman and Cora Lee

Wetherington (NIDA); and Mary Blehar, Emily Gause,

Della Hann, Howard Kurtzman, Ellen Leibenluft,

Delores Parron, and Jane Pearson (NIMH).

References

Alfier, T., Ruble, D.N., Higgins, E.T. (1996) Gender stereotypes during adolescence: Developmental changes and the

transition to junior high school. Dev Psychol 32(6):1129–37.

Beary, M.D., Lacey, J.H., and Merry, J. (1986). Alcoholism 

and eating disorders in women of fertile age. Br J Addiction

81:685–89.

Blehar, M.C. and Oren, D.A. (1995) Women’s increased vulnerability to mood disorders: Integrating psychobiology and

epidemiology. Depression 3:3–12.

Boyd, C., Blow, F., and Orgain, L. (1993). Gender differences

among African-American substance abusers. J Psychoactive

Drugs 25(4):301–305.

Boyd, C., Gutherie, B., Pohl, J., Whitmarsh, J., and Henderson, D. (1994). African-American women who smoke crack

cocaine: sexual trauma and the mother-daughter relationship.

J Psychoactive Drugs 26(3):243–47.

Centers for Disease Control and Prevention. HIV/AIDS 

Surveill Rep 1995; 7(no. 1):10.

Foa, E.B., Hearst-Ikeda, D., and Perry, K.J. (1995) Evaluation

of a brief cognitive-behavioral program for the prevention of

chronic PTSD in recent assault victims. J Consult Clin Psychol

63:948–55.

Griffin, M.L., Weiss, R.D. Mirin, S.M., and Lange, U. (1989).

A comparison of male and female cocaine abusers. Arch Gen

Psychiatry 46:122–26.

Heckman, T.G., Kelly, J.A., Sikkema, K., Cargill, V., Norman,

A., Fuqua, W., Wagstaff, D., Solomon, L., Roffman, R., Crumble, D., Perry, M., Winett, R., Anderson, E., Mercer, M.B., and

Hoffman, R. (1995). HIV risk characteristics of young adult,

adult, and older adult women who live in inner-city housing

developments: implications for prevention. J Women’s Health

4(4):397–406.

Hobfoll, S., Jackson., E., Lavin, J., and Britton, P.J. (1994).

Reducing inner-city women’s AIDS risk activities: a study 

of single, pregnant women. Health Psychol 13:397–403.
60

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Hudson, J.I., Weiss, R.D., Pope, H.D. Jr., McElroy, S.K., 

and Mirin, S.M. (1992). Eating disorders in hospitalized 

substance abusers. Am J Alcohol Abuse 18:75–85.

Jonas, J.M., Gold, M.S., Sweeney, D., and Pottash, A.L.C.

(1987). Eating disorders and cocaine abuse: a survey of 

259 cocaine abusers. J Clin Psychiatry 48:47–50.

Kalichman, S.C. and Coley, B. (1995). Context framing 

to enhance HIV-antibody-testing messages targeted to

African-American women. Health Psychol 14:247–54.

Kandel, D.B., Jamaguchi, K., and Chen, K. (1992). Stages 

of progression in drug involvement from adolescence to

adulthood: further evidence for the gateway theory. J 

Studies Alcohol 53(5):447–57.

Kelly, J.A., Murphy, D.A., Washington, C.D., Wilson, T.S.,

Koob, J.J., Davis, D.R., Lepezma, G., and Davantes, B.

(1994). Effects of HIV/AIDS prevention groups for high-risk

women in urban clinics. Am J Public Health 84:1918–22.

Kendler, K.S., Kessler, R.C., Walters, E.E., MacLean, C.,

Neale, M.C., Heath, A.C., and Eaves, L.J. (1995) Stressful 

life events, genetic liability, and onset of an episode of major

depression in women. Am J Psychiatry 152(6):833–42.

Kessler, R.C., McGonagle, K.A., Zhao, S., Nelson, C.B.,

Hughes, M., Eshleman, S., Hans Ulrich, W., and Kendler, 

K.S. (1994). Effects of HIV/AIDS prevention groups for 

high-risk women in urban clinics. Lifetime 12-month 

prevalence of DSM-III-R psychiatric disorders in the 

United States: results from the National Comorbidity 

Survey. Arch Gen Psychiatry 51:8–19.
Reproductive Health

BACKGROUND

The discussions of the Working Group on

Reproductive Health built on a foundation of

three components: (1) the changing status of

reproductive health in women’s health research, (2) the

Hunt Valley Report, and (3) an outline of topics developed by the cochairs as a framework for discussion.

As an area of research, the female reproductive system has fallen in and out of favor with the biomedical

establishment. Historically, “women’s health research”

was limited to the study of obstetrics and gynecology.

In the 1970s, however, societal shifts including, most

notably, feminist concerns about women’s interactions

with the medical system, resulted in broadening the

research agenda to encompass a more comprehensive

definition of women’s health. This agenda drew attention

to the lack of research on the major causes of morbidity and mortality in women, including cardiovascular

disease and cancer (especially breast cancer), and to 

the problem of ineffective or inappropriate treatment 

of diseases and conditions. As the agenda broadened,

the focus on women’s reproductive capacity was seen 

as a form of medical reductionism, and research on

female reproduction fell out of the mainstream.

Not until the late 1980s through the early 1990s,

in the context of increased government attention to and

funding of women’s health research,1 did the female

reproductive system begin to make its way back onto

the research agenda. The Hunt Valley Report, produced

during this period, reflected this renewed interest in

the papers of working groups that examined the current issues in women’s health from two perspectives:

(1) from a developmental perspective, looking at

women’s health throughout the life span; and (2) from 

a basic science perspective, looking at women’s health

in terms of the state of current biological knowledge. 

The Hunt Valley Report set out a series of questions intended to guide the women’s health research

agenda. The questions about female reproduction

encompassed basic biology and clinical practice. The

report emphasized the need for research on the physiology of the female reproductive system; on the links

between sex hormones and human behavior; and on

the etiology and treatment of a number of reproductive

abnormalities including preterm labor, polycystic ovary

syndrome (PCOS), premenstrual syndrome (PMS),

endometriosis, and uterine fibroids. From a developmental perspective, the report called for research on

sexually transmitted diseases (STDs) and contraception

(particularly pertinent to adolescent and young adult

women) and for attention to menopause issues including, most prominently, hormone replacement therapy

(HRT). In addition, the Hunt Valley Report emphasized

the need for interdisciplinary work to study the effect

of social context on women’s health.2

The present Working Group on Reproductive

Health (the change in terminology reflects the intent to

broaden the perspective of the field) has built directly

upon the foci and recommendations of the Hunt Valley

Report. Using the report, the cochairs developed a

Cochairs

Donna Vogel, M.D., Ph.D.

National Institute of Child Health and 

Human Development

National Institutes of Health

Eugene Washington, M.D., M.P.H., M.Sc.

University of California at San Francisco

Michelle Berlin, M.D., M.P.H.

University of Pennsylvania

Rapporteur: Nora Jacobsen

61

VOLUME 4
62

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

framework to help the working group participants

structure their discussions. The framework delineates content areas (i.e., reproductive health, reproductive disorders, and special populations) and

research strategies (i.e., basic biology, clinical 

research, and social and behavioral approaches). 

Working within the matrix formed by content and 

strategy, the working group addressed the agenda —

progress, gaps in knowledge, change in questions, 

and research recommendations — set by NIH’s 

Office of Research on Women’s Health (ORWH).

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT

OF ORWH

Pregnancy

Progress has occurred in four major areas of

research on pregnancy. First, knowledge has advanced

about infectious diseases during pregnancy. Recent

research has identified several infections — for example, bacterial vaginosis, chlamydia, and trichomoniasis

— in the etiology of preterm labor. In the interests of

preventing poor birth outcomes, attention has focused

on finding accurate methods to diagnose such infections and effective treatments that may be administered

during pregnancy. Continuing research on HIV/AIDS

has led to the finding that the use of antepartum and

intrapartum zidovudine (AZT) appears to reduce the

risk of perinatal transmission of the virus. 

Second, knowledge has advanced about the 

prevention of fetal malformations. Improvements in

genetic testing and prenatal diagnosis have provided

parents with better information for making choices

about whether to continue a pregnancy of a malformed

fetus. There is greater understanding of the role of

maternal nutritional factors in the development of fetal

malformations. Recent research on the role of folic acid

(a B vitamin) in preventing neural tube defects (spina

bifida and anencephaly) has led to the recommendation that all women of childbearing age consume 0.4

mg of folate per day and that folate be added as a 

supplement to bread and other grain products. 

The third area of progress has been in identifying

risk factors for preterm labor. Screening for the presence of fetal fibronectin in the vagina or cervix of a

pregnant woman seems to hold promise as a predictor

of preterm labor. The presence of fetal fibronectin also

appears to be a good indicator of upper reproductive

tract infection in pregnant women. The link between

vaginal infections and preterm delivery suggests that

screening and, if necessary, treatment of high-risk

women might have potential in preventing poor birth

outcomes. Data have improved on the disparities in

preterm delivery rates among racial and ethnic groups.

Preterm delivery rates may be higher among AfricanAmerican women because they have higher rates of

reproductive tract infection. The new research confirms 

a likely heterogeneity in the etiology of preterm labor. 

Fourth, in the social and behavioral realm, there

has been progress in understanding and promoting

measures to improve the health of women during 

pregnancy. Recognition of the safety and benefits 

of exercise, increased awareness (among health care

providers and pregnant women) of the detrimental

effects of alcohol consumption during pregnancy, 

legislation prohibiting smoking in public places,

improved management of ectopic gestation, and 

new methods of medical abortion have all improved 

the health of the pregnant woman.

Contraception

Progress has been made in several areas of research

on contraception: the development of new methods

(and the reintroduction of some old ones), research on

the safety of existing methods, and recognition of the

need for a new generation of contraceptive technologies.

Since Hunt Valley, Norplant (levonorgestrel subdermal implants), Depo-Provera (medroxy-progesterone

acetate injection), and the female condom have all been

introduced to women in the United States. The innovative delivery systems used in Norplant and DepoProvera seem particularly promising for adolescent

women. The female condom has met with problems 

— cost, ease of use, provider resistance — but has 
63

VOLUME 4

been shown to be popular among women who have

received good health education and support. The concerns about HIV/AIDS that prompted the development

of the female condom have led to a resurgence in the

use of the male condom. Recently, women and providers also have taken a new look at the intrauterine

device. Finally, progress has been made in the area of

emergency contraception. The Food and Drug Administration issued an advisory regarding off-label use of

mifepristone (RU 486) and oral contraceptives for 

postcoital contraception (“morning after pill”). 

Perhaps most important is the increased awareness on the part of researchers and clinicians of the

need for new methods. This awareness derives from

research showing the ambivalence of certain racial/

ethnic groups about using some methods and, more

broadly, the recognition that women need different

contraceptive choices at different periods of their lives.

The worldwide epidemic of STDs has led to calls for

the development of new microbicides and microbicide/spermicide combinations. Early research on these

combination methods looks promising. In addition,

some progress has been made in developing a new

male contraceptive — a hormonal injection being 

tested by international researchers.

Infertility

Substantial progress has occurred in the treatment

of infertility and understanding of the many etiologies

of the condition. Technological advances have included

many new (or improved) assisted reproductive technologies: in vitro fertilization, embryo transfer, the use

of donor eggs, and intracytoplasmic sperm injection;

laser surgery for the treatment of pelvic inflammatory

disease; the use of GnRH analogs in ovulation induction; and improved provider expertise at using these

technologies. In addition, the recent expansion in

knowledge about ovarian physiology and conception

(e.g., the timing of intercourse relative to the LH surge

and the importance of egg quality) promises to result

in new clinical applications. 

Advances also were made in understanding the 

etiologies of infertility. The evidence does not support

the suggestion that video display terminals are a cause

of recurrent spontaneous abortion. Research on the

part played by STDs in causing infertility has led to the

development of a screening test (urine PCR) for

chlamydial infection. Early detection of chlamydial

infection can reduce the development of pelvic 

inflammatory disease, thus preventing later problems with infertility. A provocative new area of 

research is the role played by cell-mediated 

immunity in male and female infertility. 

Progress has been made in the psychosocial and

policy areas relevant to infertility treatment. There has

been an increased awareness of the trend toward women’s

delaying first birth3 and the necessity for quick, appropriate treatment in those cases. Policy and science have

interacted in the field: science has influenced policy

(e.g., institution of screening for chlamydia) and policy

has influenced science (e.g., development of qualitycontrol guidelines for infertility clinics).

Ectopic Gestation

Diagnosis and treatment of ectopic gestation have

improved, thus reducing associated morbidity and

mortality. Specifically, transvaginal ultrasound and the

timely measurement of serial hCG have improved diagnosis. New treatments, including methotrexate, have

improved medical management and reduced the need

for surgical intervention.

Ovarian Failure

Much of the progress in ovarian disorders has 

been in increased awareness of their definition and

prevalence. Conceptually, the recent distinction made

between ovarian failure and “premature menopause”

has been extremely important. In some cases, premature ovarian failure can remit, with return of cyclic

menses and ovulation. There has been a recognition 

of iatrogenic ovarian failure. Clinicians and researchers

have determined the inefficacy of estrogen and ovulation induction to treat the condition. 
64

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS), which

involves absent or disturbed ovulation and excessive

androgen secretion, is a leading cause of female infertility and is difficult to treat. There has been a new

awareness of the occurrence of PCOS in adolescent 

and middle-aged women. Research has shown a link

between PCOS and increased risk for diabetes, cardiovascular disease, and breast cancer. The role of insulin

resistance in the etiology of PCOS has been recognized,

and researchers are looking at the use of insulin sensitizers and a follicle-stimulating hormone for treatment.

Endometriosis

Awareness of endometriosis has increased, and

health care providers and researchers are more likely 

to take it seriously. Retrograde menstruation now is

recognized to be a background condition, not a sole

cause. Laser treatment to remove endometrial masses is

not thought to be efficacious, but infertility caused by

endometriosis may be successfully corrected through

assisted reproductive technologies. An exciting area 

of research is the role of abnormal cell-cell adhesion

molecules in endometriosis. Realization that biological

activity of this disease may not correlate well with 

the appearance of lesions, has cast doubt on the 

usefulness of the current classification scheme.

Myoma

Researchers have begun to make progress in 

determining the etiology of myoma. Active research 

is seeking to elucidate the roles played by gap junction proteins and the extracellular matrix. Among

providers, there is a decreased concern about malignancy and a trend toward more conservative management (i.e., treating for symptoms, not presence).

There has been some progress in treatment — an

improved radiographic technique for assessing presence and severity, laparoscopy for removal, and the 

use of GnRH analogs for the treatment of anemia

before surgical removal.

Abnormal Uterine Bleeding

There is an increased awareness among clinicians

and researchers of abnormal uterine bleeding. Progress

has been made in understanding the differences

between normal menstrual shedding and abnormal

bleeding. Research is focusing on the endometrium

itself and the control of uterine vasculature.

Pelvic Floor Relaxation

Researchers have begun to recognize the 

neuromuscular etiology of pelvic floor relaxation. 

In addition, surgical methods to treat it have 

improved, resulting in less morbidity.

Pelvic Pain

Pelvic pain has been recognized as a condition, 

but it has not yet been well defined. Researchers 

have presented preliminary findings suggesting a

myofascial etiology. Most progress, perhaps, has been 

in the recognition of the psychosocial ramifications 

of this condition among women and their families.

Premenstrual Syndrome

Awareness has increased of the variability of definition and presentation of premenstrual syndrome, 

as well as of its multifactorial etiology. There is more

knowledge about which treatments are not effective

(e.g., vitamin B-6, evening primrose oil). Promise exists

in the seeming efficacy of GnRH analogs for the suppression of ovulation and in the use of sophisticated

imaging technologies to describe the neurological and

endocrine pathways involved in the condition.

General Issues

While progress in specific strategic areas has 

been uneven, there was a consensus that awareness 

of all conditions has improved and that such awareness could help serve as a blueprint for the future. 

A general theme in the working group’s discussion 

of progress was the idea that even negative results 

in research, that is, results that do not support the
65

VOLUME 4

hypothesis of the research, represent an advance in 

that they narrow the specific avenues of inquiry. As 

one participant noted, “We know a lot more about

what we do not know.”

GAPS IN KNOWLEDGE

Pregnancy

There are gaps in all areas of knowledge about

pregnancy. Research is needed on the basic biology of

preterm labor, growth restriction, preeclampsia, and

spontaneous abortion. Better data are required on the

sociodemographic correlates of pregnancy outcomes,

including data on the effects of race/ethnicity, poverty,

abuse/battering, housing instability, and immigration.

Little is known about postpartum depression or the use

of alternative therapies during pregnancy. In addition,

there is a need for technology assessment and outcomes research on many of the medical interventions

related to pregnancy care (e.g., home uterine monitoring, cesarean section, prenatal care). Such outcomes

research should look at both short-term and longitudinal outcomes of treatment and use multidimensional

measures for assessment. Researchers should begin to

look at the pharmacodynamics and pharmacokinetics

of drug therapies during pregnancy. Finally, more work

needs to be done to determine the effects of pregnancy

(or of never being pregnant) on women’s health

throughout the life span.

Contraception

Three major topics related to contraception are 

priorities for research. First, research is needed to

determine the long-term effects of currently available

methods — in particular, the metabolic and long-term

effects of hormonal methods and the possible role of

the intrauterine device in causing primary tubal infertility. Second, options for contraception should be

expanded through the development of new methods.

Research should focus on immunologic methods, on 

a reversible method for men, on new microbicide/

spermicides (as well as on microbicides that are not

spermicides), and on new materials for barrier contraceptives. Recent research points to a need for better

provider knowledge of certain methods — the IUD 

and the female condom. Finally, there is a tremendous

dearth of knowledge of the psychosocial context in

which women (and men) choose and use (or do not

use) contraceptives, especially about decisionmaking

related to contraceptive choice and the determinants 

of early, unprotected intercourse.

Infertility

There are gaps in current knowledge about almost

all aspects of infertility. Questions remain about the

epidemiology of infertility, about the role of environmental and occupational exposures in the etiology of

some types of infertility, about the psychosocial aspects

of infertility (e.g., the social/psychological effects of

anonymous egg donation), and about male infertility.

Too little is known about the effectiveness of specific

treatments in specific populations, the quality of infertility treatment, and the cost effectiveness of currently

available treatments. In addition, there is a lack of

knowledge about the long-term effects of certain treatments for infertility (e.g., the possibility of a link

between ovulation induction and later development 

of ovarian cancer). Many questions remain about recurrent spontaneous abortion — etiology (including

the role played by environmental and occupational

exposures), epidemiology, the immunology and

endocrinology of the condition, and management 

(e.g., the effectiveness of bed rest). Finally, there 

is a gap between the advances in basic science 

and the clinical application of this knowledge.

Ectopic Gestation

Research is needed to determine the epidemiology

of ectopic gestation. More needs to be learned about

the role of local effectors, biochemical stimuli, cytokines, douching, and other factors in the etiology of 

the condition. Research also is needed to determine 

the long-term effects (for example, on fertility) of 

using medical instead of surgical treatment.
66

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Ovarian Failure

A multitude of questions remain about disorders 

of ovulation. In contrast to the relative ease of treating

infertility due to hypothalamic or pituitary hormone

deficiency, premature ovarian failure is extremely difficult to treat. Gaps in knowledge exist about almost

every aspect: connections between epidemiology and

etiology (e.g., the possible role of smoking and occupational/environmental exposures in ovarian failure);

pathophysiology; markers of reversibility or remission;

and somatic, psychosocial, and functional effects of

ovarian dysfunction. 

Polycystic Ovary Syndrome 

Polycystic ovary syndrome is now recognized as an

important cause of infertility and of morbidity even in

women not trying to conceive. More work is needed 

on the complex hormonal interactions involved in the

etiology and pathogenesis of this common and distressing condition. In this way, improved treatments can be

devised based on a foundation of scientific knowledge. 

Endometriosis

Little is known about the epidemiology and etiology of endometriosis and how to treat it effectively.

The pathway by which the condition causes infertility

remains unclear. Research is needed to establish the

impact of the condition on women’s quality of life and

economic functioning. Perhaps the greatest need is for

noninvasive markers to aid early identification of these

conditions. Such markers would facilitate identification

of risk factors, early diagnosis, and better monitoring 

of treatment. It is expected that this would make conservative management more viable, and thus more

attractive to both providers and patients, reducing 

the use of hysterectomy.

Myoma

Studies of the epidemiology and etiology of

myoma are needed. Technology assessment of laparoscopic and other treatments (including alternative

therapies) must be performed to provide better 

management. Questions remain about the implications of large fibroids and pregnancy, about hormone

replacement therapy and regrowth of fibroids in 

postmenopausal women, and about the use of GnRH

analog treatment. New combination or low-dose 

therapies need to be developed that will control

myoma symptoms yet avoid the somatic effects of 

estrogen deficiency seen with present regimens. 

There is a need for education of the public and 

professionals on the issue of treating intolerable 

symptoms, not simply presence of myomas.

Abnormal Uterine Bleeding

Research is needed to determine treatment effectiveness and to look at the long-term effects of treatments currently in use (e.g., endometrial ablation).

Pelvic Floor Relaxation

Little is known about the etiology or pathophysiology of pelvic floor relaxation. More attention should be

paid to finding effective treatments with minimal complications. Questions remain about the effectiveness of

physical therapy, Kegel exercises, and biofeedback in

ameliorating the condition. Perhaps most important,

research should look at how management of labor and

delivery might be changed to prevent its occurrence.

Pelvic Pain

Very little is known about pelvic pain. A clear 

definition and effective management strategies are

needed. In addition, research is needed on the psychosocial issues involved (e.g., the link between 

sexual abuse and pelvic pain).

Premenstrual Syndrome

Work is needed to better define PMS and to

explore what it can teach us about the connection

between hormones and behavior. Too little is known

about the quality of life issues for women who suffer

from the condition. Research on treatment should 

look at the use of antidepressant medications and 

the role that complementary therapies might play 

in ameliorating symptoms.
67

VOLUME 4

Special Populations

No rigorous data exist on reproductive health 

in women with disabilities. Too little is known about

issues of access to care for reproductive health services

in underserved populations (e.g., adolescents and

minority women) and the phenomenon of differential

treatment for women from different socioeconomic

groups. In addition, more attention should be paid 

to understanding the cultural aspects of reproductive

health (e.g., acculturation and favorable birth outcomes

among ethnic subpopulations and immigrant groups;

female genital mutilation).

General Issues

Two themes recurred in the working group’s discussion of gaps in knowledge. The first theme was the

impact of new systems of reimbursement on medical

research and practice. Because the effects of managed

care on quality of care have yet to be determined and

because of the new emphasis on cost in the medical

setting, the working group saw a great need for studies

in the areas of outcomes research and cost-effectiveness

assessment. Although aware that such research traditionally has not fallen under the NIH research mandate, the working group suggested that the increased

importance of such issues might argue for more flexibility. The second theme was the difficulty of acquiring

funds for research on conditions such as pelvic pain

and PMS. Because such newly recognized conditions

are believed to have psychogenic components, it is

unclear which NIH institute has purview over them.

This point led to a more general observation: many

health concerns of women cut across various aspects 

of their lives, such as physical, emotional, and social;

however, the NIH structure is organized by disciplines

and organ systems. This mismatch makes it difficult to

institute the multidisciplinary approaches best suited 

to studying women’s health.

CHANGE IN QUESTIONS

SINCE HUNT VALLEY

The managed care environment is prompting

researchers and clinicians to ask questions about 

outcomes and the cost effectiveness of current and 

new treatments. Outcomes are being conceptualized

broadly, encompassing multidimensional measures

(e.g., quality of life) and longitudinal designs. Perceived problems with the new reimbursement systems 

are prompting questions about access to care for

underserved populations and quality of care for all

patients. A related change is the need for better education of generalists (because they function as gatekeepers) to increase their awareness of reproductive

health issues and to improve their competence in 

treating these conditions, including when to refer 

to a specialist.

While discussing progress made in understanding

pregnancy and improving pregnancy care, the working

group noted that although many of the advances were

directed at improving the health of the fetus, attention

recently has shifted to a concern for the woman during

pregnancy. Many of the interventions to improve 

maternal health are social, directed at lifestyle, rather

than biological. 

In contraception research, only recently has attention turned to the man’s role in contraception. New

questions are being asked about contraceptive technologies that serve women’s and men’s broader needs

across the life span. In infertility research the importance of psychosocial issues has come to be understood. The demographic shift — women delaying 

their first pregnancy until well into their 30s — has

driven the demand for infertility services. That demographic shift is prompting researchers and clinicians to

ask new questions about when to begin to treat infertility, about how far treatment should go, and about the

meaning of infertility in women’s and men’s lives.

Changes in policy and technology also have

shaped the questions being asked about women’s 

reproductive health. NIH’s policy guidelines requiring
68

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

the inclusion of women in clinical trials4 will give

researchers an opportunity to look at the pharmacodynamics, pharmacokinetics, and pharmacoeconomics

of drugs in women of reproductive age. Advances 

in computerization technology have improved data 

collection, thus expanding the kinds of research 

questions that may be pursued.

A final change — a paradigm shift in the field 

of reproductive health — has been the recognition of

heterogeneity: women are different from one another,

and individuals vary across the life span. The integration of this paradigm of heterogeneity into the reproductive health research agenda promises to fulfill the

expectation implicit in the term “reproductive health”

and to change the scientific questions.

RESEARCH 

RECOMMENDATIONS

Pregnancy

The working group’s research recommendations reflect its assessment of the two most pressing

problems in this area — preterm labor and maternal

health — and the need for continuing to emphasize 

the social context of reproductive health. The working group recommends:

• research on the basic biology of preterm labor 

and the role of social factors; and 

• research on the effects of external factors — lifestyle,

pharmacology, and environmental and occupational

exposures — on the health of pregnant women.

Contraception

These recommendations reflect the increased concern with understanding the psychosocial factors

involved in contraception. They also focus on the 

serious problem of STDs among women of reproductive age, particularly adolescent women. The 

working group recommends:

• research on contraceptive-use behavior 

(decisionmaking and compliance);

• research leading to the development of contraceptive options appropriate under different circumstances and for different populations; and

• research on interactions between contraceptives

and STDs.

Infertility

The working group’s recommendations emphasize

the importance of conceptualizing infertility as the

problem of a couple and also of developing more 

specific and efficacious management strategies. The 

recommendations call for:

• recognition that infertility is a problem of the 

couple in which the male factor must not be

neglected; and

• efficacy research on management strategies for

more focused treatment selection based on the biomedical and psychological needs of each couple.

The research recommendations for the following

reproductive disorders reflect the very preliminary

stage of current knowledge about the biology and management of these conditions.

Ectopic Gestation

The working group recommends research on the

etiology and risk factors of ectopic gestation and on the

efficacy and long-term effects of current and evolving

management of this condition. Data are needed on

whether maintaining tubal integrity through conservative management results in preservation of fertility

potential and a decrease in repeat ectopic gestation.

The HPO Axis (Polycystic Ovary Syndrome, 

Anovulation, and Ovarian Failure)

The working group recommends research on the

etiology and pathophysiology of ovarian dysfunction,

on the amelioration of infertility, and on the long-term

effects of these conditions and their treatments on 

general health.
69

VOLUME 4

Endometriosis, Myoma, and Abnormal 

Uterine Bleeding

The working group recommends:

• research to find noninvasive markers of disease

activity (endometriosis) to establish prevalence 

and risk factors; and

• recognition of the inadequacy of current therapies

and the need for an understanding of pathophysiology to develop new and better treatment options.

References

1 Kirschstein, R.L. 1992. Introduction. Report of the National Institutes of Health: Opportunities for Research on Women’s

Health. Bethesda, MD: The National Institutes of Health.

2 Hazzard, W.R. and M.L. Polan. 1992. Overview. Report of

the National Institutes of Health: Opportunities for Research

on Women’s Health. Bethesda, MD: The National Institutes

of Health.

3 Mosher, W.D. and W.F. Pratt. 1993. The demography 

of infertility in the United States. In Annual Progress in

Reproductive Medicine, R.H. Asch and J.W.W. Studd 

(eds.). New York: The Parthenon Publishing Group.

4 Rothenberg, K.H., et al. May-June 1996. The NIH 

inclusion guidelines: Challenges for the future. 

IRB 18, no. 3: 1–4.

Cancer

BACKGROUND

Although the death rates for many cancers 

have decreased over the last 20 years, 

cancer remains the leading cause of death 

for women 35 to 74 years old. In 1997, an estimated

596,600 women will be diagnosed with cancer, and

265,900 women will die from the disease.1 Lung 

cancer now surpasses breast cancer as the leading 

cause of cancer deaths for women, followed by 

cancers of the breast, colon, and rectum. Cancer

remains a major public health problem, causing 

untold anxiety and suffering for patients and their 

families, as well as generating a substantial part 

of the nation’s health care expenditures.

SCIENTIFIC PROGRESS

SINCE ESTABLISHMENT 

OF ORWH

The major event since Hunt Valley in 1991 is the

decrease in the U.S. cancer mortality for the first time. 

In addition, the field of genetics has advanced the 

scientific understanding of cancer significantly. The

genetic loci for some hereditary cancers of the breast,

colon, endometrium and the ovary have been identified. Already, inherited susceptibility to cancer accounts

for 5 to 10 percent of these cancers. This number is

likely to increase as other genetic factors are identified.

Further, the genetic pathways responsible for the loss

of normal cellular-control mechanisms may lead to 

an understanding of the process of carcinogenesis in

sporadic (or nonfamilial) cancers. Furthermore,

research has demonstrated similar changes in oncogenes and tumor-suppressor genes across many 

cancers, suggesting common mechanisms of loss 

of cell cycle control. 

The links between infectious agents and some cancers have also been clarified since 1991. These include

the association between H. Pylori and gastric cancer,

specific human papilloma viruses and cancers of the

cervix and vulva, the Epstein-Barr virus and Burkitt’s

lymphoma, nasopharyngeal carcinomas and leiomyosarcomas, and human herpes virus 8 (HHV8) and

Kaposi’s sarcoma. The observation that integration of 

the viral genome into the host DNA is necessary for

carcinogenesis suggests a mechanism for viral carcinogenesis in cancer etiology.

Broad population-based studies have documented

the impact of diet and lifestyle in the development of

cancers of the head and neck, esophagus, stomach, and

colon. These observations have fostered the design of

intervention trials; attempts to change diet or habits 

to reduce the incidence cancer. The fall in cancer mortality underscores the importance of research into diet

and environmental factors in carcinogenesis, as well 

as screening and more effective treatments.

Since Hunt Valley, differences in response to carcinogens, drug metabolism, and response to treatment

have been observed between women and men, between

different racial and ethnic groups, and between older

Cochairs

Edward Trimble, M.D., M.P.H.

National Cancer Institute

National Institutes of Health

Karen Antman, M.D.

Columbia University

Rapporteur: Rea Kerr Howarth

71

VOLUME 4
72

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

and younger individuals. For example, compared to

men, women develop lung cancer after lower doses

and shorter intervals of cigarette smoking. Research 

has begun to describe the interplay of genetic, environmental, socioeconomic, and other factors which

determine whether an individual will develop cancer

and whether that cancer responds to treatment.

Since 1991, important advances have occurred in

cancer therapy. These include chemotherapeutic agents

with novel mechanisms of action, such as paclitaxel

and topotecan. 5 FU and leucovorin have been shown 

to be effective in preventing recurrences in patients

with stage 3 colon cancer. The use of minimal access

surgery, which has the potential to decrease morbidity

and improve quality of life for cancer patients, has

become much more common. Multi-modal, organsparing therapy has been proven effective in treating

breast, laryngeal, and rectal cancers.

In the years since Hunt Valley, consumer and

patient advocates have strengthened. These groups

have helped focus the nation’s attention on a variety 

of critical cancer issues, including laboratory research,

prevention, education, screening, treatment, and survivorship. They have helped set priorities for research

and have become involved in the design and conduct

of prevention, screening, and treatment trials. Consumer groups and cancer investigators have also

strengthened research on quality-of-life issues for 

those undergoing treatment for cancer and for cancer

survivors who have completed primary treatment.

Since 1991, major changes have occurred in 

health care delivery. Enrollment in health maintenance

organizations and other managed-care organizations

has increased dramatically. Many cancer patients have

reported difficulties in gaining referrals to the appropriate cancer specialists, as well as in gaining access to

NCI-sponsored cancer trials and treatment at NCIdesignated cancer centers. Changes in reimbursement

have limited investigator time and institutional monies

available to support basic and clinical research. These

changes, together with the persistence of a major 

portion of the population without health insurance,

have had a major impact on the conduct of basic 

and clinical cancer research.

CHANGE IN QUESTIONS

SINCE HUNT VALLEY

The areas of scientific progress and societal change

since 1991 have also expanded the questions considered critical in cancer research. For example, genetic

advances in cancer required addressing the medical,

social, ethical, and legal issues of screening for genetic

abnormalities. Knowledge about the heterogeneous 

etiology of cancer, including genetics, diet, cigarette

smoking, and hormonal and environmental influences,

has led to small- and large-scale cancer prevention 

trials. These have included evaluation of retinoids in

the prevention of secondary lung and head and neck

cancers, as well as of tamoxifen in the prevention of

secondary breast cancers and breast cancer recurrences.

Consumer and patient advocate groups have appropriately encouraged a closer look at quality-of-life

issues during and after cancer treatment.

In this report, the working group addresses 

gaps in knowledge about the most common malignancies affecting women, including cancers of the 

lung, breast, colorectum, uterine corpus, cervix, 

and ovary. General research and policy recommendations are presented below.

GAPS IN KNOWLEDGE

Lung Cancer

In 1992, lung cancer was the cause of death for 

54,348 American women. The American Cancer Society (ACS) estimates that 64,000 women died of lung

cancer in 1996,2 25 percent of all cancer deaths among

women. The incidence of lung cancer varies by gender

and ethnicity, representing historical patterns of cigarette smoking. In 1990, for example, the incidence 
73

VOLUME 4

of lung cancer per 100,000 individuals was 78.6 

for white men, compared to 41.5 for white women, 

116 for black men, and 45.3 for black women.3

Among women, the number of adenocarcinomas 

of the lung, a type of lung cancer less associated 

with tobacco smoke, is rising.

Recent molecular evidence definitely links tobacco

smoke with cancer causation. Men and women appear

to respond differently to the carcinogens found in

tobacco smoke. Compared to men, women develop

lung cancer after smoking fewer cigarettes over a 

shorter period of time. There is some evidence that 

vitamins A, C, E, selenium, and other micronutrients

may be beneficial in preventing lung cancer.4 Diets 

rich in fruits and vegetables appear to lower the risk 

of lung cancer by up to 50 percent. Epidemiology 

studies of lung cancer may help identify other potential chemopreventive agents, as well as the etiologic

agents for pulmonary adenocarcinomas.

Smoking cigarettes has been identified as a risk

factor not only for lung cancer, but also for cancers of

the mouth, larynx, pancreas, bladder, kidney, cervix,

and vulva. Prevention of smoking onset, therefore,

would decrease the risk of lung and other cancers and

chronic lung disease. Since 90 percent of all smokers

report that they began smoking during their teens, 

the key to primary prevention is to prevent smoking

among adolescents and young adults. Unfortunately,

smoking rates, which had previously been falling

among adults, are now increasing. In 1994, 48 million

adults reported smoking, compared to 46 million in

1993. Twenty-eight percent of men smoke, and 23 

percent of women smoke. Almost three-quarters (71

percent) of high school students have tried cigarettes.5

The most urgent research priority must be 

focused on optimizing prevention efforts targeted 

to children and adolescents. Education about the

health hazards of smoking, beginning in early childhood and repeated into adolescence, may be effective.

Recognition of the role of peer pressure and the urge 

to rebel against adult authority must be incorporated

into educational strategies.

Messages should be nuanced to address a variety 

of ethnic, racial, and socioeconomic groups, and to

counteract the pro-tobacco messages promulgated 

by cigarette advertising and promotions. Advertising

aimed at adolescents and young adults, which connects smoking with slenderness, social activity, and

popularity, exercises a powerful impact on adolescent

girls. Specific advertising campaigns aimed at black 

and Hispanic young women, which may have sparked

recent increased usage among these groups, must be

challenged in the public forum. Research must determine the optimal forum of oppositional advertising.

Self-esteem issues such as weight, peer pressure, 

mood, and depression also play a role in the decision 

of many young girls to smoke. Researchers should 

focus on these factors to develop effective antismoking messages for this age group.

Nicotine, a stimulant which can ameliorate negative emotions such as depression, may be particularly

important to women who have higher rates of depression and, as a group, take more mood-modifying 

medications than do men. Research should examine 

the interactions among gender, mood modulation, 

and smoking patterns and their relevance to prevention and cessation interventions.

Ongoing research into optimal strategies for 

smoking cessation should focus on the many influences in smoking behavior from peer groups, school,

work site, and the community institutions in which

women participate. Clinical and research findings suggest that social support can play a significant role in

successful smoking cessation, particularly for women.

Additional research on the role of social support in

smoking cessation is recommended. 

Smoking Average Among High School Students

White Black Hispanic

Boys 37% 28% 35%

Girls 40% 12% 33%
74

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Smokers whose parents have had lung cancer are

twice as likely to develop lung cancer as the general

population of smokers. Research to address genetic 

and metabolic risks for lung cancer, as well as cessation approaches and supports for this more vulnerable

population, is also important.

Phase I, II, and III chemopreventive trials are

needed to prevent first and second primary lung cancers. Large-scale screening approaches for people at

risk could have a major impact on death rates. The

National Cancer Institute is supporting a randomized

study of screening with chest radiography as part of the

Prostate, Lung, Colon, and Ovarian Cancer Screening

Trial (PLCO). Development of reliable biomarkers and

imaging technologies are urgently needed to improve

the early detection of lung cancer.

Advances in cancer treatment are urgently needed,

since only 16 percent of individuals with lung cancer

are alive 5 years after diagnosis.6 The timely completion of randomized clinical trials evaluating surgery,

chemotherapy, and radiation therapy are critical to

progress in the treatment of lung cancer. These studies

should be large enough to address the interaction

issues of gender and race/ethnicity with treatment. 

All Americans must have access to the appropriate 

cancer specialists, as well as to lung cancer prevention programs, screening, and treatment trials.

Breast Cancer

The incidence of breast cancer per 100,000

women rose dramatically between 1980 and 1987,

from 85 to 112, but it appears to have leveled off 

in 1990 with a rate of 109 per 100,000 women.7

In 1996, the National Cancer Institute (NCI) estimates that 184,300 women were diagnosed with 

breast cancer, and 44,300 died of the disease. For 

the first time, the mortality rate appears to be 

falling, particularly for premenopausal women.

Understanding the etiology of breast cancer is 

critical to developing new prevention, diagnosis, and

treatment strategies. Research priorities include the

basic biology of the breast, mechanisms of carcinogenesis, and genetic, hormonal, reproductive, environmental, and other factors. For example, changes in the

dose or schedules of hormonal contraception and hormonal replacement therapy might reduce the risk for

breast cancer and significantly lower the incidence of

breast cancer. Study of plant-based phyto-estrogens

could prove useful. As the development of breast cancer is better understood, detection of precancerous

lesions may become more accurate. New imaging

modalities may help to identify persons at high risk 

for developing breast cancer, as well as identify 

smaller cancers before metastasis has occurred.

Prevention trials have been initiated. The Breast

Cancer Prevention Trial, which is evaluating tamoxifen

versus placebo for 5 years in women at high risk for

breast cancer, will complete its accrual of 13,000

women shortly. Phase I, II, and III trials of new preventive strategies, particularly important for women at

high familial risk for breast cancer, should continue.

Data continue to support the use of routine 

screening mammography for detecting breast cancer.

Between 1983 and 1990, the incidence of detection 

of in situ cancers rose.8

Black women continue to have a lower survival

rate than white women. The 5-year survival rate for

white women diagnosed between 1986 and 1991 was

84 percent, whereas it was only 69 percent for black

women.9 A recent study suggests that 75 percent of 

the difference in survival between black and white

women may be explained by late diagnosis, tumor

characteristics, concomitant illness, and social and

demographic factors.10

Detection of In Situ Cancer Cases in 1990 Compared to 1983

Aged < 50 Years Aged > 50 Years

(Percent) (Percent)

Black 131 150

White 82 157
75

VOLUME 4

Data from the 1992 National Health Interview Survey indicate that only 30 percent of women age 50 

or older had a mammogram during the previous year.

Poverty and lack of insurance are the chief factors associated with low utilization. Improved access to screening

and education to increase utilization rates for all ages

and racial/ethnic groups would be a major priority.

Major progress has been made in the identification

of genetic loci responsible for many cases of familial

breast and ovarian cancer. In 1994, two of the most

common genetic loci, BRCA1 and BRCA2, were isolated.

Fifty percent of women with mutations in BRCA1 and

a strong family history will develop breast cancer by

age 50 and 85 percent by age 70.11 These discoveries,

however, introduce new questions. Tests for mutations

in BRCA1 and BRCA2 are now commercially available.

The ethical, legal, and social implications of such testing deserve study. Under what conditions are these

tests most helpful and least harmful to women and

their families?

Treatment issues remain of great importance.

Developmental diagnostics may help better define

which women with breast cancer may be safely treated

with surgery alone, and which would benefit from

adjuvant chemotherapy or radiotherapy. The activity 

of new drugs, such as paclitaxel and taxotere, in breast

cancer suggests that we can improve adjuvant and salvage chemotherapeutic regimes. The effectiveness of

tamoxifen in reducing the risk of recurrent or contralateral breast cancer supports further investigation of

endocrine therapy for both prevention and treatment.

The efficacy of high-dose chemotherapy, coupled with

hematologic support (stem cell transplant), is currently

under evaluation in randomized, controlled clinical 

trials. Finally, an area for active study is how to

improve the quality of life after treatment for breast 

cancer; for example, ways to restore a positive body

image and sexuality, ensure fertility after adjuvant

chemotherapy, and prevent osteoporosis after 

surgical or natural menopause.

Cancer of the Reproductive System

Corpus Uteri. A projection based on SEER data is

that 34,000 women will be diagnosed with cancer of

the uterus in 1996; 6,000 will die of the disease. Most

of these cancers arise in the endometrial lining of the

uterus (endometrial adenocarcinoma); the remainder

arise in the muscle wall at the uterus (uterine sarcomas

and carcinosarcomas).

Risk factors for endometrial adenocarcinoma

include anovulation, obesity, diabetes, and estrogen

unopposed by progesterone. Elevated estrogen levels

may be endogenous (associated with obesity or certain

ovarian tumors), or exogenous (from estrogen replacement therapy or tamoxifen). Protective factors include

pregnancy, lactation, and oral contraceptives. Atypical

endometrial hyperplasia is a precancerous lesion.

Research on the basic biology of endometrial cancers, uterine sarcomas, and carcinosarcomas is critical

to develop effective prevention and treatment programs.

Clinical trials aimed at preventing endometrial

cancer should be encouraged, particularly for obese 

or anovulatory women or women on tamoxifen or

unopposed estrogens.

Eighty percent of women with endometrial cancer

develop abnormal vaginal bleeding, prompting early

evaluation and treatment, usually hysterectomy. The

role of ultrasound in screening for endometrial cancer

deserves further evaluation.

Mortality from endometrial cancer is higher 

for black women (6.0 per 100,000) than for white

women (3.3 per 100,000).12 Although the time from

onset of symptoms to treatment appears similar for

black and white women, the incidence of carcinomas associated with normal estrogen levels is higher

among black women. These tumors are associated 

with higher stage at diagnosis, greater propensity 

to metastasis, and worse survival. A better understanding of the biology of endometrial cancer may 

facilitate development of prevention and treatment

strategies for endometrial cancers.
76

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

The association of many cases of endometrial 

cancer with elevated estrogen levels, however, suggests

that progesterone might be an effective prevention for

women with atypical endometrial hyperplasia, thus

sparing some women a hysterectomy. Other clinical 

trials might evaluate the role of laproscopic surgery, adjuvant radiotherapy, and chemotherapy, as well as systemic chemotherapy for patients with metastatic disease.

Cervical Cancer. The estimated number of American women with a new diagnosis of cervical cancer in

1996 was 15,700; some 4,900 women are estimated to

have died of the disease.13 Worldwide, cervical cancer

is second only to breast cancer in incidence and mortality from cancer. More than 471,000 new cases are

diagnosed each year, predominantly among the economically disadvantaged, in both developing and

industrialized nations.

Invasive cervical cancers and precursor lesions

have been firmly associated with the presence of specific strains of sexually transmitted human papilloma

virus (HPV). Studies have demonstrated that the HPV

genes E6 and E7 are integrated into the host genome

and inactivate P53 and Rb, thus resulting in malignancy.

The prevalence of infection decreases with increasing

age suggesting that most infections resolve over time

through host-immune responses. Cigarette smoking 

is a co-factor in humans. Other factors under study

include use of oral contraceptives, number of live

births, age at first intercourse, co-infection with other

sexually transmitted diseases, and immune response

including growth factors, cytokines, and humoral 

and cellular immunity. Immunosuppressed women,

whether due to corticosteroids or HIV infection, 

are at increased risk for precursor cervical lesions 

and cervical cancer.

Primary prevention of HPV infection will require 

(1) directing education efforts toward adolescents 

and health care providers regarding the strong causal

link between the acquisition of HPV as a sexually transmitted disease and the development of cervical cancer;

(2) encouraging delayed onset of sexual intercourse;

and (3) developing effective vaginal microbicides. 

Secondary preventive efforts must focus on the 

development of effective antiviral agents to treat 

HPV and/or prevent transformation by E6/E7 and 

of therapeutic vaccines to prevent HPV progression.

Squamous cell cervical cancer is an ideal disease

for screening because of the typically long preclinical

phase, which provides the opportunity for early detection. Use of the Pap smear is effective in reducing morbidity and mortality from cervical cancer. Despite the

recognized benefits of Pap smear screening, many

American women have not been screened or are not

screened at regular intervals. One-half of women with

newly diagnosed invasive cervical carcinoma have

never had a Pap smear, and another 10 percent have

not had a Pap smear in the past 5 years. The inadequately screened populations include older women, 

the uninsured, ethnic minorities (especially Hispanics

and elderly blacks), and poor women, particularly

those in rural areas. Data from the 1992 Health Interview Survey indicate that one-half of all women 

60 years old and older have not had a Pap smear 

in the past 3 years.14 Older women are screened 

less frequently, despite the same number of recent

physician visits as younger women, indicating the 

need to educate older women and their health care

providers about the importance of Pap smear screening. Reasons for nonparticipation in screening should 

be identified and appropriate interventions studied.

Research to improve current screening technology

should be encouraged. Liquid-based specimen collection methods are currently under study. Automated

instruments for screening smears, recently approved by

the Food and Drug Administration, need further evaluation in routine primary screening and in subsequent

screening. Their cost effectiveness should be evaluated.

Optimal management of patients with certain precursor lesions, atypical cells of undetermined significance, and low-grade squamous intra-epithilial lesion 

is not established. A large NCI clinical trial is currently

evaluating the different ways to manage these patients.
77

VOLUME 4

Strategies to develop more accurate imaging 

studies would better define the extent of disease 

at presentation as well as to plan radiation therapy.

Currently, no category of cervical adenocarcinoma,

which could be treated conservatively to preserve 

fertility, can be identified. Clinical trials should define

the benefit of neoadjuvant chemotherapy. Progress in

developmental diagnostics may identify which patients

with disease confined to the cervix might benefit from

adjuvant therapy after hysterectomy. The optimal adjuvant regimen for patients with disease confined to the

pelvis, whether radiation, chemotherapy, or both, has

not yet been defined. Clinical trials are also needed to

define the role, if any, of prophylactic or therapeutic

para-aortic node radiation.

Defining any impact of P53 status and HPV 

subtypes may allow customizing of treatment strategies. Dose-response relationship, time-dose relationship, improvements in technical instrumentation, and

optimization of brachytherapy techniques should be

further studied. Predictive assays for tumor and/or normal tissue radiation sensitivity might allow individualization of radiation prescriptives. Strategies to reverse

anemia and tissue hypoxia could improve the radiation

responsiveness of the tumor. The optimal management

of HIV-positive women with precursor lesions and 

cervical cancer remains to be determined.

Ovarian Cancer. Ovarian cancer accounts for 

about 4 percent of all cancers in women and 6.7 percent of all cancer deaths. In 1996, about 26,700 new

cases of ovarian cancer will be diagnosed in the United

States, and 19,800 women will die of ovarian cancer.

Known risk factors include BRCA1 and BRCA2 abnormalities; advancing age; nulliparity; North American 

or Northern European descent; a personal history of

endometrial, colon, or breast cancer; and a family history of ovarian cancer. Protective factors include pregnancy, lactation, and the use of oral contraceptives. 

A better understanding of the epidemiology, genetics,

and biology of ovarian cancer is critical. 

Based on current data on the etiology of ovarian 

cancer, prevention trials are problematic. Nonetheless,

the population-based data on the protective effect of

birth control pills, as well as some preliminary data 

on retinoids, suggests that prevention trials can be

designed for high-risk individuals. Data on the incidence of ovarian cancer in women with BRCA1 

mutations who undergo prophylactic oophorectomy are critical.

There is no effective screening test or combination of tests for ovarian cancer.15 Screening tests 

currently in use include serum, gynecologic exams,

CA-125, and transvaginal ultrasound. Even when 

used together, the sensitivity, specificity, and positive

predictive value are inadequate to warrant their use 

in the general population. NCI’s PLCO trial is currently evaluating the combination of transvaginal 

ultrasound and CA-125 screening for ovarian 

cancer. Other strategies should be evaluated.

A recent study showed that only 14 percent of

women with early-stage ovarian cancer received the

recommended surgical staging and treatment. In 40

percent of cases reviewed, no pathologic grade was

assigned to the cancers removed.

Women should be informed of the need to have

doctors with the appropriate expertise in gynecologic

cancer surgery and pathology available at the time 

of their surgery. In patients with advanced disease,

optimal surgical debulking followed by appropriate

paclitaxel and platinum-based chemotherapy prolongs

survival. More effective adjuvant therapy is required.

Intraperitoneal therapy, immunotherapy, radiotherapy,

and high-dose chemotherapy with hematologic support

are current research strategies. The current Phase III

trial of high-dose chemotherapy versus standard consolidation therapy should be promoted. New regimens

for women with recurrent or persistent ovarian cancer

should be constructed and evaluated with survival 

and quality of life as the major end points.
78

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Colorectal Cancer

In 1997, an estimated 65,900 women will be 

diagnosed with cancer of the colon or rectum and

24,300 will die of the disease. Familial adenomatous

polyposis coli and familial non-polyposis colon cancer

(Lynch II) are the most common familial syndromes.

Since the Hunt Valley conference, multiple genetic 

loci for these syndromes have been identified. 

Factors decreasing colon cancer risk include exercise; a low-calorie, low-fat, high-fiber diet; estrogen

replacement therapy; aspirin; and nonsteroidal antiinflammatory agents. Prospective, randomized prevention trials should evaluate these and other agents.

Keys to early detection include an annual digital

rectal examination after age 40, and yearly stool tests

for occult blood and a baseline sigmoidoscopy after 

age 50. The role of screening colonoscopy remains 

controversial. A more accurate screening method than

fecal screening for occult blood is needed. Imaging

techniques which could augment or replace signoidoscopy/colonoscopy merit study. Recent studies have

shown that women are not being screened for colon

cancer. Secondary prevention efforts must include 

evaluation of new strategies to educate both women 

and their physicians about the benefits of screening 

for colon cancer.

Many treatment-related questions remain 

unanswered. The current intergroup phase III trial 

is evaluating minimal access surgery in early colon 

cancer. After primary surgery in patients with Stage 3

colon cancer, the combination of 5FU and leucovorin 

is effective in reducing recurrences and death from

colon cancer; 6 months of therapy rather than 12

months appears adequate. Since Hunt Valley, several

new drugs have demonstrated activity in colon cancer.

New agents and combinations need to be evaluated 

to improve adjuvant therapy. Local approaches such 

as cryotherapy should be evaluated for women with

colon cancer metastatic to the liver.

Neoadjuvant chemoradiation has been effective in

preserving normal rectal sphincter function in patients

with rectal cancer. Improvements in chemotherapy and

radiation therapy may improve long-term survival in

patients with locally advanced rectal cancer.

RESEARCH 

RECOMMENDATIONS

• While a major recent focus in cancer research has

been on genetic factors in carcinogenesis, the federal research portfolio should be balanced with

substantial funding for epidemiology, prevention,

screening, treatment, and quality of life as well as

other aspects of molecular and tumor biology. 

• Research on genetic factors in familial cancer has

produced new commercially available tests, which

may allow individuals from affected families to

assess their personal risk. The social, ethical, legal,

and economic effects of the availability of these

tests must continue to be carefully studied.

• Research on how to communicate risks and 

how to encourage health-promoting behavior

remains a high priority. Communicating the 

risks of smoking and preventing the initiation 

of smoking by children and adolescents remains 

our only effective strategy in lung cancer. We 

need to communicate the risks of early sexual

activity, and of multiple sexual partners (or 

of sexual partners who have had multiple partners), and to encourage appropriate behavioral

changes to decrease the transmission of human

papilloma virus, HIV, and thus the risk of cervical cancer, and HIV-associated lymphoma 

and Kaposi’s sarcoma.

• Emerging patterns in tumor incidence, such as 

the increased incidence of pancreatic cancers,

melanoma, and brain tumors, as well as of adenocarcinomas of the lung, esophagus, and cervix,

may define new etiology factors.
79

VOLUME 4

• The ethical and legal implications of research on

tissues stored in repositories must be carefully

assessed, particularly involving issues of consent 

and confidentiality.

• Epidemiologic studies need to evaluate the 

interaction between genetic factors and 

environmental and endogenous carcinogens 

in cancer causation.

• Managed care has transformed the delivery 

and economics of health care, increasing stresses 

on academic medical centers and hampering 

education, research, and sometimes patient care.

Access of all Americans to optimal cancer treatment and representation of women and minorities

in clinical trials are high priorities. Barriers to 

participation in cancer screening and prevention

programs, and access to appropriate specialists,

clinical trials, and treatment in cancer centers, 

are unethical and shortsighted.

• Forty-one million U.S. citizens are without health

insurance. Many more are inadequately insured.

Uninsured individuals often do not have access 

to prevention or screening programs. Therefore,

precancerous lesions and early cancers may go

undiagnosed and untreated. They may finally 

seek medical care when treatment is no longer

effective. The medical research community must

work with policy makers to ensure that adequate

access to health care is viewed as a basic human

right and that health promotion becomes part 

of the activities of daily living.

• To facilitate evidence-based medical practice, 

we must support coordination of information 

and research results on clinical trials. 

References

1 Parker, S.L., T. Tong, S. Bolden, and P.A. Wingo. 

January and February 1997. Cancer statistics, 1997. 

CA Cancer J Clinicians 47, no. 1: 5–28.

2 Ibid.

3 Kessler, L.G., J.H. Lubin, and E. Feigal. Report on 

Lung and Bronchus Cancers. Bethesda, MD: National 

Cancer Institute.

4 Lung disease data – 996. American Lung Association.

5 Kann, L., C. Warren, W. Harris, J. Collins, B. Williams, 

J. Ross, and L. Kolbe. September 27, 1996. Youth risk

behavior surveillanc – United States, 1995. CDC 

Morbidity and Mortality Weekly Report 45, no. SS–4.

6 Cancer facts and figures – 1996. American Cancer Society.

7 Hankey, B.F., L.A. Brinton, L.G. Kessler, and J. Abrams.

Breast. Bethesda, MD: National Cancer Institute. Source:

Dr. Ted Trimble.

8 Ibid.

9 See footnote 1.

10 Eley, J.W. and B. Edwards. 1994. Racial differences 

in survival from breast cancer. JAMA 272: 947–54.

11 Breast Cancer Facts and Figures 1996. American 

Cancer Society. 

12 Kosary, C., L.A. Brinton, and E.R. Trimble. Corpus 

Uteri. Bethesda, MD: National Cancer Institute. 

13 See footnote 1.

14 Cancer Risk Report, Prevention and Control 1995.

American Cancer Society. 

15 Gloeckler Ries, L.A., P. Hartge, and E. Trimble. 

Ovary. Bethesda, MD: National Cancer Institute. 

Source: Trimble.

Research Designs: 

Multidisciplinary 

Perspectives

How can synergy between scientific disciplines be

achieved through a multidisciplinary perspective that 

incorporates biomedical, psychosocial, and socioeconomic

approaches to women’s health research?

Research aimed ultimately at improving the

health of women and subpopulations of

women across the life span focuses on a 

broad spectrum of factors. Investigations may examine basic, molecular, genetic, immunologic, and 

other mechanisms in the etiology and pathogenesis 

of disease, thus contributing to the biomedical knowledge base or to the development of innovative therapies. At the same time, psychosocial research seeks 

to improve understanding of the cultural, lifestyle, 

personality, cognitive, affective, motivational, social

support, and other factors associated with women’s

decisions to adopt or maintain healthy behaviors, or

seek health care services. In addition, socioeconomic

research seeks to better understand the effects of 

such variables as employment status and income 

on women’s health.

Much of the research on women’s health 

conducted in the past, and even today, addresses 

questions from a specific, singular perspective rather

than from a range of biomedical, psychosocial, and

socioeconomic points of view. Research projects 

involving investigators from multiple disciplines are 

not usually the norm. However, as available research

dollars shrink, innovative integration of expertise 

from various disciplines may become an increasingly

important strategy for maximizing funding potential.

During the past several years, a growing number of funding opportunities, made available through the National

Institutes of Health (NIH), have specifically encouraged

or called for multidisciplinary research teams.

Research on women’s health, because of the

encompassing nature of this area, provides a unique

opportunity to assemble researchers from multiple 

disciplines. Collaborative research projects on women’s

health can cut across disciplinary boundaries within

the basic and molecular sciences, within medicine, 

and with other disciplines including, but not limited 

to, nursing, pharmacy, anthropology, psychology, 

sociology, health education, social work, economics,

and demography. It must be noted that multidisciplinary research should not replace single-discipline

research but should supplement it, thereby enriching

understanding and permitting the development of

broad-based knowledge.

Despite the desire to encourage multidisciplinary

research on women’s health issues, there continue 

to be barriers to conducting this type of research. 

For example, academic systems typically have fewer

means of rewarding or recognizing multidisciplinary

efforts. Furthermore, there are still few funding mechanisms that focus on multidisciplinary research. Also

important is the fact that researchers have limited firsthand experience or training in building and working 

as part of multidisciplinary teams. This inexperience 

is sometimes also reflected in the evaluation of study

sections. Clearly, some changes within NIH and academic institutions are required if synergy between 

Cochairs

Patricia Grady, Ph.D., R.N.

National Institute of Nursing Research

National Institutes of Health

Brian Strom, M.D., M.P.H.

University of Pennsylvania Medial Center

Rapporteur: Susan Farer

81

VOLUME 4
82

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

disciplines is to be achieved. Overarching issues 

and specific recommendations that would encourage multidisciplinary research on women’s health 

are discussed below.

THE STRUCTURE 

OF NIH FUNDING

SHOULD ENCOURAGE

MULTIDISCIPLINARY

RESEARCH

Women’s health provides a unique, crosscutting

research realm in that it is multidisciplinary by definition, offering important opportunities for simultaneous

study of biomedical, psychosocial, and socioeconomic

variables. While opportunities for multidisciplinary

research with NIH funding do exist and are expanding,

further progress in this area should be encouraged. In

addition, coordination among NIH institutes and centers (ICs) should be heightened in support of multidisciplinary research activities, and NIH communication

about these opportunities should be enhanced. The 

following recommendations are proposed in support 

of these goals.

Identify Multi-institute Issues

Issues that cut across research disciplines and

across the missions of the NIH ICs should be identified, and funding for multidisciplinary research should

be made more readily available.

Encourage Inter- and Intra-institute 

Multidisciplinary Research

NIH should encourage the promotion and development of multidisciplinary research, both within individual ICs and across ICs. Program offices within the

Office of the NIH Director and directors of individual

ICs can play a vital role in stimulating crosscutting research by promoting research policies and funding in

support of mechanisms for multidisciplinary research.

The Office of Research on Women’s Health (ORWH),

the NIH Office on Minority Health, and NIH Office 

of Behavioral and Social Sciences Research are already

engaged in working closely with all of the NIH ICs to

enhance their respective portfolios in behavioral 

and social sciences research and to identify research

opportunities that foster trans-NIH collaborations.

Use RFA/RFP Mechanisms To Support 

Multidisciplinary Research

Despite philosophical support, NIH-funded 

multidisciplinary research will not be enhanced unless

funding mechanisms are made available for such research. Requests for application (RFA) and requests for

proposals (RFP) should be developed that specifically

seek multidisciplinary women’s health-related investigations. Furthermore, the time lines for application submissions must take into account the complexities of

developing collaborations among researchers from 

different backgrounds and perspectives.

Establish ORWH as a Broker

NIH ORWH is in a unique position to function 

as a “broker” and advocate for funding multidisciplinary women’s health research across NIH ICs. This 

broker/advocate role would be in keeping with ORWH’s

mandate “to strengthen and enhance research related 

to diseases, disorders, and conditions that affect women

and to ensure that research conducted and supported

by NIH adequately addresses issues regarding women’s

health.” By taking a leadership role, ORWH could 

provide a pivotal point for communication among the

ICs regarding multidisciplinary research on women’s

health and could proactively develop multidisciplinary

research opportunities. In addition, ORWH could serve

as a resource for investigators wishing to explore or

develop linkages with other investigators and research

programs concerned with similar research topics. 

ORWH Funding Priorities Should Explicitly 

Encourage Multidisciplinary Research

Today, ORWH vigorously implements its mandate 

to strengthen and enhance research on women’s health,

in part by providing co-funding to ongoing NIH grants

and special initiatives that have gender-specific research

objectives. In planning for the 21st century, ORWH

should identify as a priority, research that cuts across

disciplines, and then should emphasize co-funding 
83

VOLUME 4

of investigations that cut across biomedical, psychosocial, and sociocultural perspectives.

Establish Multidisciplinary Coordinating Groups

Communication across NIH ICs and within the

extramural research community is vital to increasing

opportunities for multidisciplinary research and to

building multidisciplinary teams of investigators. 

Coordinating groups, committees, and task forces 

comprising program-level IC staff with common 

interests should be established to identify shared 

goals and act upon priority women’s health research

areas. For example, the Coordinating Committee on

Research on Women’s Health, coordinated by ORWH,

brings together representatives of NIH ICs to discuss

directions for research on women’s health and provide direction to the ORWH director. Similar groups

could be established to discuss multidisciplinary

research addressing specific disease topics that affect

women, such as HIV/AIDS, autoimmune diseases, 

or heart disease.

Convene Multidisciplinary Conferences

Conferences, workshops, and symposia should be

convened to discuss research topics on women’s health

from multidisciplinary perspectives. Such meetings are

important in examining current knowledge, as well as

theoretical and methodological issues. The Women’s

Health Seminar Series, sponsored annually by ORWH,

serves as a model for such conferences, with topics

addressing such issues as genetic testing, hormone

replacement therapy, breast cancer, and domestic 

violence. The series is planned and implemented in 

conjunction with the NIH Coordinating Committee 

on Research on Women’s Health, ensuring that 

numerous perspectives are addressed.

Create Core Centers

The funding of “core centers” for research on

women’s health could be a method to encourage close

cooperation, communication, and collaboration among

investigators with similar interests who are conducting

individual research projects. The core center serves as

an identifiable organizational focal point within a 

single university medical center or among a consortium of cooperating institutions. This concept fosters

interdisciplinary cooperation and the sharing of

resources, such as instrumentation or assays, thus

enabling more efficient and productive work. Core 

centers for research on women’s health would not 

supplant investigator capabilities but would enhance

investigators’ opportunities to learn and advance. Core

centers may also provide funding for seminars, visiting

scientists, or other program-enrichment activities.

MULTIDISCIPLINARY

RESEARCH SHOULD 

BE REWARDED 

WITHIN ACADEMIC

INSTITUTIONS

NIH and academic institutions should collaborate 

to increase the amount of multidisciplinary research

conducted on women’s health issues. Institutions

should provide both philosophical support and

advancement opportunities for those who build 

bridges across biomedical, psychosocial, and socioeconomic research domains. In addition, academic

structure should follow, not dictate, research needs.

Matrices that match the multidisciplinary interests 

and expertise of individual faculty members provide

one model for encouraging crosscutting research 

within academic institutions. The following recommendations may assist institutions and faculty members in shifting toward a new way of thinking.

Encourage Promotion Criteria that Stimulate 

Multidisciplinary Research

Professional advancement in academic settings

today generally hinges on success in one’s discipline.

However, especially as federal research resources constrict, the academic environment should not discourage

but should reward faculty investigators who seek out

and develop multidisciplinary research programs. Promotion criteria should incorporate faculty members’

initiative and success in this regard.
84

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Encourage Scientists to Learn How to “Package” 

Multidisciplinary Careers

If efforts related to research on women’s health 

are to be successful, investigators need to increase 

their willingness to cross academic and disciplinary

boundaries. Individual investigators need to learn 

to channel their research to fit current models and

should draw on their multidisciplinary research 

abilities in developing their careers.

Encourage NIH-funding Mechanisms that Support

Multidisciplinary Research and Training at 

Academic Institutions

Academic institutions are more likely to encourage multidisciplinary research on women’s health if

NIH supports such research. Therefore, NIH-funding

mechanisms should encourage multidisciplinary

research and investigator training. Furthermore, 

NIH training and career development grants should 

also emphasize the importance of applications proposing multidisciplinary work.

TRAINING SHOULD BE

MULTIDISCIPLINARY

The environment in which researchers are trained 

is critical in influencing and is often a determining 

factor in the professional directions and interests of 

scientists. In the past, students of medicine, nursing,

and other professional disciplines participated in core

courses together, providing opportunities to share 

ideas and develop an awareness of varied perspectives.

Today, the academic environment may often segregate

the disciplines, thereby creating barriers to the crosspollination of ideas. In addition, NIH research training

and career development programs tend to be discipline

specific and organ specific. Training mechanisms, some

believe, are equal to or more important than funding

mechanisms in determining the amount of multidisciplinary research that is conducted. The following steps

are recommended to enhance the integration of disciplines during the crucial training years of scientists, 

as well as during the course of their research careers.

Establish Multidisciplinary Training Programs

First, there is a need to establish or reestablish 

professional training programs that require or encourage cross-disciplinary study. Such programs would shift

the learning process away from professional separatism

and toward broad-based learning. Cross-disciplinary

study would encourage students to consider the spectrum of biomedical, psychosocial, and socioeconomic

concerns that may interact to affect women’s health.

Publicize Effective Individual and Institutional 

Role Models

Individuals and academic institutions that serve 

as exceptionally effective models for multidisciplinary

training in the field of research on women’s health

should be recognized and publicized. Information

about model training initiatives that cross disciplinary

and departmental boundaries within medicine and

other disciplines should be disseminated widely

through professional meetings, journals, professional

organization publications, the Internet, and other 

print and electronic media.

Publish and Publicize the Process of Putting 

Together Multidisciplinary Teams

The process of building successful multidisciplinary teams for research on women’s health should be

documented and disseminated to encourage and teach

others to follow suit. Only through the sharing of ideas

about the team development process will these programs effectively serve as models. Information should

be disseminated widely at professional meetings, in

journals and the publications of professional organizations, on the Internet, and in other print and 

electronic media.

Recognize Mentors

Mentors play a vital role in the career development of professionals in any field. This role is even

more crucial in the relatively new field of women’s

health. Mentors who successfully build collaborative

teams and are involved in multidisciplinary training

and research efforts should be recognized and rewarded.
85

VOLUME 4

Encourage and Provide Funding Mechanisms for 

Continuing Education in Fields Other Than One’s

Area of Primary Expertise

Scientists wishing to pursue research careers in

women’s health that traverse scientific and disciplinary

boundaries must possess a practical understanding of

the concerns, science, and methodologies of fields

other than their own. Continuing education provides 

a formal means of developing this understanding,

although funding mechanisms are needed to encourage

and support researchers who wish to maximize their

capabilities in conducting multidisciplinary research.

NIH training and career development grants specifically designed for researchers wishing to study outside 

of their traditional disciplinary realms may be one

mechanism to provide such support.

Encourage NIH Institutes To Fund 

Multidisciplinary Training

To maintain a cadre of well-trained investigators 

in research on women’s health, NIH ICs should be

encouraged to fund research training and career 

development efforts that go beyond specific disciplines. Investigators-in-training, with interests in 

crosscutting research, should be considered for 

support through National Research Service Awards,

whether individual or institutional, career development awards, and fellowships.

Develop Inter-institute Review Processes and 

Funding for Training Awards

The process of reviewing and funding applications for research training and career development

often fosters single-discipline and single-organ system

approaches. If investigators-in-training in the field of

women’s health are to develop interests in multidisciplinary work, then application review policies and 

procedures should ensure review by appropriate 

multidisciplinary review groups that are also representative of multiple NIH ICs.

MULTIDISCIPLINARY

RESEARCH PROPOSALS

ARE OFTEN REVIEWED

BY SINGLE-DISCIPLINE

INDIVIDUALS

There has been a noticeable increase in the number of NIH funding opportunities that invite or require

multidisciplinary research. However, there is also a

belief within the research community that application

review committees evaluate applications for multidisciplinary projects from single-discipline perspectives and

represent the review committee’s purview. Anecdotal

accounts indicate that, in some instances, there has

been a lack of understanding on the part of reviewers

that multidisciplinary projects can truly represent highquality science, especially if the projects are innovative

and methodologically sound. Therefore, the NIH

review committee structure should be examined for its

ability to ensure that multidisciplinary research applications are evaluated by individuals who possess a clear

understanding of the disciplines and concerns involved

in multidisciplinary research projects. This issue may

be addressed through the following recommendations.

Expand Use of Ad Hoc Reviewers on 

Standing Committees

For most applications, the initial or first level of

review involves panels of experts established according

to scientific disciplines or medical specialty areas. The

function of these scientific peer review groups is to

evaluate the scientific merit of grant applications.

Expanding the use of ad hoc reviewers who represent

the behavioral and social disciplines on these standing

research review committees would help to ensure that

high-quality, multidisciplinary research projects on

women’s health are evaluated appropriately.

Use Ad Hoc Review Committees

Ad hoc review committees should also be considered for the review of multidisciplinary grant 

applications. Such committees would comprise 
86

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

representatives of multiple disciplines that cut 

across the biomedical, behavioral, and social 

sciences, depending on the application topic.

Solicit Reviewers with Appropriate 

Multidisciplinary Expertise

Selection of reviewers sitting on scientific peer

review groups is based in part on their expertise, 

experience, and knowledge of specific disciplines. 

Individuals with multidisciplinary expertise should 

be identified and made known to those scientific

review administrators who determine the composition of review committees.

Inform Applicants of How To Use Existing 

Review Structures

NIH grant applicants must learn as much about

the grant application and review process as possible.

Increased communication with applicants regarding 

the existing review structures could be accomplished

through the NIH Division of Research Grants home

page or by other means.

Identify and Publicize Successful Models

Research review committee structures that serve 

as successful models for the review of multidisciplinary grant applications should be identified and their

successes publicized so that they might be emulated

within the NIH review structure.
Racial, Ethnic, and

Cultural Diversity 

in Clinical Research

BACKGROUND

A merican women come from and continue 

to live in diverse racial, ethnic, cultural, 

and socioeconomic backgrounds. A growing number belong to groups commonly referred to 

as minorities — African American, American Indian,

Alaskan Native, Asian, Pacific Islander, and Hispanic. 

To a large extent, a woman’s health status may 

depend on the group or subgroup to which she

belongs, as is apparent in the following statistics:

• In 1993, life expectancy at birth was 79.5 years for

white women and 73.7 years for black women.1

• In every year from 1970 to 1993, heart disease 

was the leading cause of death for all women living

in the United States. However, between 1970 and

1980 the age-adjusted death rate for heart disease

was about 50 percent higher for black women than

for white women. Between 1980 and 1993, the

heart disease mortality differential between white

and black women widened to 67 percent, due to 

a more rapid decline in heart disease death rates

for white women (26 percent) than for black

women (18 percent).2

• In 1993, the age-adjusted death rate from heart

disease was 24 percent lower for American Indian

and Alaskan Native women and 43 percent lower

for Asian and Pacific Islander women than for

white women (99.3 per 100,000), and the rate 

was 29 percent lower for Hispanic women than 

for non-Hispanic white women.3

• In 1993, black women were 28 percent more likely

to die of breast cancer than were white women.4

• Since 1973, the age-adjusted incidence rate for

ovarian cancer, the most common female reproductive malignancy after breast cancer, has been

more than 50 percent higher among white 

women than among black women.5

• Most of the women diagnosed with AIDS during the 12 months ending June 30, 1995, were

black or Hispanic women (59 and 17 percent,

respectively).6

• Between 1988 and 1991, the age-adjusted prevalence of hypertension was higher for non-Hispanic

black women (31 percent) than for non-Hispanic

white women (21 percent) or Mexican-American

women (22 percent).7

• Between 1988 and 1991, being overweight was

more common among women whose family

incomes were below the poverty line than among

those with higher incomes. Among all women 20

years of age and over, the age-adjusted prevalence 

of overweight was 47 percent for women below 

the poverty line and 32 percent for those at or

above the poverty level.8

• In 1992-93, women were 6.6 times as likely as

men to experience violent crimes by a spouse, 

ex-spouse, or partner. However, the rate of violent

attacks by intimates among women in families with

annual incomes of less than $10,000 was 19.9 per

Cochairs

Virginia Cain, Ph.D.

Office of the Director

National Institutes of Health

Helen Rodriguez-Trias, M.D.

Western Consortium for Public Health

Rapporteur: Wanda Avila

87

VOLUME 4
88

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

1,000 women, compared with 4.5 per 1,000

women among those with annual incomes of

$50,000 or more.9

• In 1993, women below the poverty line were 

3.2 times as likely to be uninsured as women

above the poverty line (36 and 11 percent, 

respectively).10

• In 1993, women who lived below the poverty 

line were 57 percent more likely to lack a regular

source of medical care than women whose family

income was at or above the poverty line (16 and

10 percent, age adjusted). 11

• For women admitted to substance abuse treatment

in 1993, the type of substance abuse correlated

with race and ethnicity. Alcohol, and alcohol 

combined with another drug, were the primary

substances of abuse among non-Hispanic white

women, while cocaine was the predominant 

substance of abuse among non-Hispanic black

women, and heroin among Hispanic women.12

Despite these and other statistics that clearly 

indicate the disparities in health status among various

subpopulations of women, clinical research that has

included women at all has focused on white, middleclass, heterosexual, able-bodied women. This focus on

the majority group retards the advance of biomedical

information about minority groups, who make up over

25 percent of the population in the United States (see

Table 1), and who are different not only in biological

factors but also in cultural and behavioral factors that

are associated with health. The percentage of minority

groups in the population is increasing, and the disparity between the health status of the majority 

group and that of minority groups is widening.13

To develop the knowledge base that will yield 

benefits for minority women, enabling them to access

the remarkable advances in medicine and health care, 

population diversity must be ensured in all aspects 

of research, including training minority researchers,

awarding grants for research that includes diverse 

populations, designing research models to evaluate 

the differences among population groups, retaining

study participants from diverse populations, and 

publishing results so that the appropriate caretakers 

have access to the information.

The study of the health problems in diverse 

subgroups could also increase the knowledge base

about how to prevent and survive disease, with applications for the entire population. Research models that

study the assets on resiliencies of specific groups and

individuals might reveal the adaptive mechanisms that

make them healthy despite adverse environments. 

For example, the study of heart disease among AsianAmerican women, who have a much lower incidence 

of heart disease than women from any other racial or

ethnic group, might provide insight into the resiliency

factors and behaviors that protect from heart disease.

An examination of beneficial dietary or exercise patterns might suggest preventive strategies for all women.

NIH Guidelines on Inclusion of Women and 

Minorities in Clinical Studies

In the past 5 years, the National Institutes of

Health (NIH) has taken several steps to increase the

participation of women from minorities in clinical

studies. Most notably, early in 1994, the agency published its NIH Guidelines on the Inclusion of Women and

Minorities as Subjects in Clinical Research, which require

that researchers receiving NIH support include women 

TABLE 1 Detailed Race and Hispanic Origin of U.S. Women

1980 and 1990-1993

(Numbers in Thousands) 

1980 1990 1991 1992 1993

All persons 226,546 248,710 252,177 255,078 257,783

Women

White 99,835 106,561 107,631 108,584 109,515

Black 14,046 16,063 16,412 16,653 16,925

American Indian and 

Alaskan Native 718 1,041 1,068 1,081 1,099

Asian and Pacific

Islander 4,279 4,444 1,915 3,805 4,087

Hispanic 7,329 10,966 11,460 11,871 12,405

Source: National Center for Health Statistics. 1996. Health, United States, 1995.

Hyattsville, MD: Public Health Service.
89

VOLUME 4

and members of minority groups and their subpopulations, when appropriate, in biomedical and behavioral

research projects involving human subjects.14 NIH

issued these guidelines in response to the NIH Revitalization Act of 1993 (P.L. 103-43), which directed that

“the Director of NIH, in consultation with the Director

of the Office of Research on Women’s Health and the

Director of the Office of Research on Minority Health,

shall conduct or support outreach programs for the

recruitment of women and members of minority

groups as subjects in projects of clinical research.” 

The goal of this requirement is to increase the opportunities for obtaining critically important information

with which to enhance health and treat disease among

all Americans, and to detect and account for significant differences between genders or racial and ethnic

groups where they exist.

The guidelines also strengthened the previous 

policies published in the NIH Guide for Grants and 

Contracts, 1990, which required that NIH staff and peer

advisory groups “ensure that applications/proposals for

extramural support for clinical research studies involving human subjects include appropriate representation

of women and minorities, unless a compelling justification is made for their exclusion or inadequate representation.”15 The guidelines required NIH to take three

additional actions: (1) ensure that women and minorities and their subpopulations are included in phase III

clinical trials in a way that differences in intervention

effect can be analyzed, (2) reject cost as an acceptable

reason for excluding these groups, and (3) initiate programs and support for outreach efforts to recruit these

groups into clinical studies.

Ethical Issues for Institutions and IRBs to Consider

The importance of including women and minority

groups in health research must be balanced against the

right of individuals to refuse to participate in research.

To facilitate that process, in 1994, NIH’s Office of Protection from Research Risks issued a report outlining

the responsibilities of institutions and institutional review boards (IRBs) that are responsible for protecting

the rights of study participants in their consideration 

of ethical issues surrounding the inclusion of women

and minorities in research.16 The report lists seven 

key responsibilities:

1. To provide investigators with written guidance

clearly delineating expectations for inclusion of

both genders and minorities in the design and 

conduct of research.

2. To specify that, when scientifically appropriate,

investigators show how the research will address

any difference in the way a health situation or

intervention in the proposed research may affect

one gender or minority group. Investigators should

be prepared to describe the extent to which both

genders and minority groups have been involved 

in similar research.

3. To review the extent to which investigators are collaborating with researchers at other institutions to

ensure representation and sufficient involvement 

of participants of both genders from the various

minority groups. The review of such information 

is particularly important in phase III clinical trials.

4. To consider whether cash or material reimbursements are appropriate to the educational level and

socioeconomic status of the study participants and

to ensure that these reimbursements do not promote coercion or undue influence to participate 

or remain in the study.

5. To ensure that consent documents have been translated appropriately or that translators are available

when the study participants include speakers of

foreign languages or those who are illiterate.

6. To include women and members of minority

groups on the IRB, especially if the nature and 

volume of the research to be conducted at the 

institution routinely includes these populations.

IRBs should also consider consulting ad hoc 

advisors who could help with understanding the

perspectives of various groups. Also, institutions 

and IRBs can encourage investigators to seek out
90

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

such perspectives during the planning of 

research protocols.

7. To require that NIH-supported investigators specify

the gender and racial or ethnic composition of the

subject population, as well as their criteria for

including or excluding any subpopulation, or to

provide a clear rationale for excluding such information from the background data for the protocol.

Training of Minority Researchers

The diverse views that women and minorities

could bring to bear on the research agenda have been

significantly absent. Diverse populations pose diverse

and challenging issues that can be better researched

and understood only by a creative variety of research

approaches. Researchers who are homogenous in culture and experience are less likely to generate rich 

and varied research concepts than researchers who 

are diverse. Many people believe that clinical research

to date has focused on the health status of white men

because most investigators are themselves white men.

One of the best ways to improve the quality and quantity of research and alter its focus is to increase the

number of women and minority investigators. An additional advantage to cultural diversity among researchers

is the enhanced effectiveness of recruiting the participation of women from minority communities.

Since 1989, NIH has encouraged the training 

of minority researchers through such programs as its

Minority Research Supplement Program, which provides supplements to minority high school and college

students, graduate research assistants, individuals in

postdoctoral training, and investigators. In fiscal year

1990, NIH provided minority supplements to 376

members of ethnic groups: black (226), Hispanic

(114), Native American (20), Pacific Islander (10), 

and unknown (6).17

Collaborative programs between majority and

minority institutions can provide important training

opportunities for the students at both institutions. A

program established between Tulane University and

Xavier University, a black university in New Orleans,

provides a model for other institutions who want to

increase the number of minority investigators. The two

universities have established the Center for Bioenvironmental Research (CBR), which investigates the causes

and effects of environmental problems and devises

practical solutions for them.18 One way in which the

CBR fosters training for minority researchers is by 

offering fellowships to minority students of outstanding

academic achievement and scholarly promise who have

been formally admitted to a Ph.D. program and whose

research topic is environmentally related. For the academic year 1996-1997, two minority women were

among the six recipients of fellowships. Both women

are graduate students in the molecular and cellular

biology program. One will study the identification of

phytosterols that have anti-estrogenic activity in breast

and endometrial cancers. The second will investigate

mechanisms of lung injury induced by environmental

agents such as air pollutants and allergens.19 The CBR

also provides opportunities for investigators to work

with minority communities. For example, CBR members provide an ongoing occupational health research

and advisory function for the Southern Louisiana

Industry Council, placing special emphasis on minority health. CBR’s Coping with Community Stressors

Program examines minority community responses to

environmental risks, and the Environmental Justice

Partnership Project addresses the environmental research, education, and outreach needs of community

groups along the Mississippi River chemical corridor.

Also, in cooperation with the U.S. Department of

Housing and Urban Development, CBR members 

are working with residents of a public housing 

community in New Orleans to identify and act 

on environmental health issues.

Designing the Study To Include Minority Women

In planning clinical research, the NIH guidelines

encourage investigators to first consider whether their

scientific questions or hypotheses make the inclusion

of minority women in the study appropriate. Investigators may limit the population to women from a single

minority group if their scientific questions or hypotheses apply to majority women as well, and if the 
91

VOLUME 4

condition to be studied is more severe or prevalent

among a particular group of minority women than

among majority women, or if less is known about 

the disease or treatment in minority women than 

in majority women.

For an NIH-defined phase III clinical trial, the

investigator should determine whether important

minority differences are to be expected in the intervention effect. (NIH defines a phase III clinical trial 

as a broad-based clinical investigation to evaluate an

experimental intervention in comparison with a standard or control intervention or to compare two or

more existing treatments.) If so, the investigator 

should design the trial so that the intervention effect 

can be tested for minorities or their subpopulations. 

Understanding the Study Population

To obtain valid data, researchers must clearly

define the populations they are studying. Countries 

of origin, immigration status, level of acculturation,

socioeconomic status, and cultural and linguistic characteristics vary widely. A cultural or racial label for a

minority group may fail to reflect the heterogeneity of

individuals or groups to which the label is applied. For

example, the label “Southeast Asian” refers to Philippine, Hmong, Laotian, Vietnamese, and Cambodian

peoples, and the term “Native Americans” is used to

describe more than 500 federally recognized tribes.

Similarly, “Hispanic/Latino” populations include Mexicans, Puerto Ricans, Cubans, and other Central and

South Americans whose ethnic origins and racial characteristics are varied. Yet, health studies on “Hispanics”

commonly include a larger number of Mexican Americans (who constitute almost 65 percent of the Hispanic

population in the United States) than members of any

other Hispanic subpopulation. Generalizations based on

data from these participants may be valid for Mexican

Americans, but invalid for Hispanics of other origins.

An understanding of cultural and linguistic differences is essential to ensuring that methods used in

screening and interviewing are culturally sensitive. For

example, the Hmong have views regarding blood that

prohibit its sampling. Some groups take offense at

questions about sexual issues. One recent recruitment

effort among black women students at Howard University failed because the women thought that the

questions about sexual behavior were inappropriate,

and they simply refused to answer them. In addition,

important linguistic differences often exist among

speakers of the same language who come from different countries; an inoffensive word for an Puerto Rican,

for example, may be an obscenity for a Mexican.

Collaboration with the Community

Successful research efforts in minority communities depend on collaboration with members of the 

community at every phase of the research. Community leaders and other residents, as well as the study

participants themselves, should be involved in setting

research goals, designing appropriate methods for

informing the target population about the planned

research, determining appropriate instruments for 

collecting data, and evaluating outcomes.

A major barrier to recruitment in many minority

communities might be distrust of scientific researchers

because of historical incidents of abuses of research by

outside organizations and researchers, or because they

may feel that the researchers have been insensitive to

the health concerns of their community. Therefore,

enlisting the support of community leaders may be

essential to gaining access to a community. Researchers

who meet with community leaders to define the health

or disease problems they want to study and to explain

the benefits and risks of the research are likely to find

that the leaders are eager to provide a perspective on

the cultural, behavioral, social, and economic factors

that may contribute to or interfere with the research

protocol. The community leaders can also help researchers form networks with other community 

organizations that will facilitate development and 

acceptance of the planned research. 

Collaboration with religious leaders has been

found to be especially useful for several reasons. First,

churches are usually interested in participating in 
92

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

primary prevention efforts, operating health care and

wellness programs of their own. Also, since churches

serve as natural community centers, establishing the

church as the place of contact between researchers 

and participants partially eliminates the transportation

problems that constitute a barrier to participation in

studies. Furthermore, churches tend to involve entire

families. The importance of the family among many

minority groups makes the inclusion of the individual’s

family desirable in dealing with the individual’s health

problems. For example, smoking cessation research

shows that Latino men are more likely to stop smoking

if they are encouraged to do so to benefit their wives

and children. In the African-American community, 

too, a health care project is always a family project. 

Ministers and other community leaders may also

be able to help researchers gain access to those populations who can most benefit from the research effort,

such as those minority women who never use the

health care system or who use it only at times of crisis.

Too often, researchers in minority communities have

had to select their samples from the people who have

access to health care, simply because they had no

access to those who most needed health care.

Community leaders and other members can also

help define the problem to be studied, ensuring that

the priorities of the researchers pose no conflict with

those of the participants. For example, a community

concerned with alcoholism, drug abuse, and AIDS 

may have little interest in participating in a study 

on dietary cholesterol. 

Recruitment and retention efforts are much more

likely to be successful if the recruiters are local residents of the same race and ethnicity as the defined

study population. At one west Philadelphia clinic, for

example, nurse practitioners are collaborating with the

principal investigators from the university in a highly

successful weight loss program for black women. Also, 

a study on how to reduce prenatal transmission of

AIDS in southeastern Pennsylvania is using HIVpositive women as part of the investigative team. 

The researchers trained the women in how to gather

data through personal interviews and telephone conversations. As a result, the women have a sense of

accomplishment, and the project has reported a 

tenfold improvement in access to information.

Local residents may also have better insight into

the problems that are causing participants to drop out

of a study. For example, researchers assume that low

retention is the result of child care and transportation

problems, only to find out that the real reasons are

quite different. Community residents may be able to

suggest ways to retain participants in the study, such 

as by setting up a network relationship among the 

participants so that they will remind each other to 

visit the clinic at the appointed time. 

Giving Back to the Community

Researchers in minority communities have a moral

obligation to give something back — whether that

return be health care, education and training, or even

employment. Several institutions have established programs that can serve as models for a reciprocal relationship between researchers and the communities 

in which they work:

• The Emory School of Nursing has opened 

clinics in what are called “undeveloped” 

poor neighborhoods. 

• At the University of Wisconsin, professors from 

the School of Nursing and health professionals

donate their time on evenings and weekends to 

a community center. They also do intensive community education. In return, they ask the community to participate in their research projects. 

• In setting up the Navajo Research Program in early

1996, an institutional review board was first established to ensure that researchers would benefit the

health of the Navajo people. The board asks

researchers to (1) provide educational materials 

to help the people or the Navajo service providers,

(2) train the Navajo staff in existing health care
93

VOLUME 4

facilities and programs, and (3) return to the 

reservation when the research is completed to

explain the results of their studies in layman’s

terms and to explain the significance of those 

studies for the Navajo people.

Publication of Research Results and Experiences

Published research data should show results by

gender and minority group status. In spite of the general recognition of the importance of including minority

women as study participants, journals still frequently

publish studies that give no information on the race 

or ethnicity of the populations studied. For example, 

a recent survey of all the articles published in the New

England Journal of Medicine in 1995 revealed that 80

percent of the articles gave no information on the

race/ethnicity of the populations studied.

Biomedical science would also benefit from

increased reporting of research outcomes, successful

and unsuccessful, involving minority groups. Although

many research institutions have developed excellent

relationships with minority communities, they have 

not published these experiences, which would be 

useful to other investigators. 

Social, Cultural, and Psychological Issues

Clinical research is needed that takes into account

the social, cultural, and psychological issues relevant 

to health, especially in the study of health problems of

minority women. More studies are needed on the ways

that the cultural and social environments of minority

women, and their perceptions of these environments,

influence their health and quality of life. Working

member felt that progress in minority health research

depends on developing and applying research models

that integrate quantitative and qualitative methods to

study the social, economic, and biomedical determinants of health. A holistic approach that overcomes the

false dichotomy between body and mind is needed. In

that vein, a study of black working class women and

black professional men, conducted by epidemiologists

at the Harvard School of Public Health and the Kaiser

Foundation Research Institute, found a link between

hypertension and race, gender, and socioeconomic

class, and between hypertension and the way in which

an individual reacts to the perceived discrimination.20

More research of this type is needed to understand how

the variables of race, class, and gender affect health.

RECOMMENDATIONS

The Working Group on Racial, Ethnic, and Cultural Diversity recommended the following ways in

which NIH can more effectively involve and benefit

diverse communities of women in research projects:

• Give peer review groups strict criteria to follow 

in reviewing grant applications and proposals,

specifying requirements as to gender, race, and 

ethnicity of study participants.

• Diversify peer review groups, ensuring that they

include women and minorities.

• Encourage collaborative research with minority

institutions, states, and communities.

• Award more grants to minority women 

investigators.

• Examine the cultural and financial barriers to 

the participation of low-income populations 

in research.

• Increase the number of supplemental awards 

to minority students.

• Meet with journal editors to encourage them to

require that clinical studies report data classified 

by race and ethnicity. 

• Encourage researchers to publish their experiences, successful and unsuccessful, in working 

with minority populations.

• Establish a clearinghouse for the publication of

research experiences with minority populations.

• Relax guidelines for inclusion in studies so that

potential participants are not excluded from studies
94

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

because they have some disease or condition 

that makes them ineligible to participate. 

• Encourage a more comprehensive approach to 

the study of health problems of minority women

than the traditional medical model allows.

• Encourage the development of research models 

that study population assets and resiliencies that

prevent disease and promote survival.

The working group also recommended the following ways in which investigators can more effectively

involve and benefit diverse communities of women 

in research projects:

• Report data by gender and racial and ethnic 

categories.

• Analyze the data for their previously published 

studies by gender, race, and ethnicity, and 

publish an addendum to the studies.

• Report experiences, successful and unsuccessful,

working with participants from diverse racial, 

ethnic, and cultural groups.

• Design more studies that are homogeneous in

terms of ethnic and racial groups in order to 

find out more about a particular group.

• Collaborate on research projects with researchers

who have access to other populations, using the

same variables. 

• Examine substance abuse and violence in the 

general population, not only in low-income 

populations.

• Design more studies to include two groups of

women who are now usually excluded from clinical studies: handicapped women and lesbians.

• Ask women within the community to collaborate

on projects by helping to identify the problem to

be studied, suggesting appropriate recruitment

strategies and methods of data collection, and 

participating in the analysis and interpretation 

of study results.

• Include the participants’ families in subgroups

where family is of great importance.

• Collaborate with community church groups in

planning, conducting, and evaluating research.

• Collaborate with churches on research in minority

communities, where appropriate.

• Reach out to those minority women who never

enter the health care system or who do so only 

at a time of crisis.

• Develop culturally appropriate instrumentation 

and outcome measures.

• Determine what participants themselves want 

to achieve through participation in the study.

• Examine barriers to health care from the participants’ point of view, which may differ radically

from the researcher’s preconceptions as to what 

the barriers are.

• Use a qualitative model of health care rather than 

a quantitative model so that researchers can understand what the health care needs of the community

are and how well they are meeting those needs.

• In some situations, establish community-based centers for research, much like the community centers

that have been established for HIV and drug abuse.

• Find ways to give back to the community through

providing health care, education and training, and

employment.
95

VOLUME 4

References

1 National Center for Health Statistics. 1996. Health, United

States, 1995. Hyattsville, MD: Public Health Service, p. 17.

2 Health, United States, 1995, p. 21.

3 Health, United States, 1995, p. 21.

4 Health, United States, 1995, p. 22. 

5 Health, United States, 1995, p. 25. 

6 Health, United States, 1995, p. 26.

7 Health, United States, 1995, p. 34. 

8 Health, United States, 1995, p. 39.

9 Bachman, R. and L.E. Saltzman. 1995. Violence against

women: Estimates from the redesigned survey. U.S. Department of Justice, Office of Justice Programs, Bureau of 

|Justice Statistics.

10 Health, United States, 1995, p. 45.

11 Health, United States, 1995, p. 46.

12 Health, United States, 1995, p. 55. 

13 Council of Economic Advisers for the President’s Initiative on Race. Changing America: Indicators of Social 

and Economic Well-being by Race and Hispanic Origin.

September 1998. pp. 4, 40.

14 NIH guidelines on the inclusion of women and minorities as subjects in clinical research. Federal Register, 

March 1994. 

15 NIH Guide for Grants and Contracts, 1990. 

16 Office of Protection from Research Risks (OPRR). 

Inclusion of women and minorities in research. 

OPRR Reports 94–01, Bethesda, MD: OPRR. 

17 Rene, A. and J. Fakunding. 1992. Support of minority

training and career development in the biomedical and

biobehavioral sciences by the National Institutes of

Health. In Health Behavior Research in Minority Populations: Access, Design, and Implementation. Washington,

D.C.: National Institutes of Health. NIH pub. no.

92–2965.

18 Allen, A. 1996. The synergy of Tulane and Xavier 

Universities. Environmental Forum, no. l, 5. 

19 Gresh, C. 1996. CBR Scholars program. Environmental

Forum, no. l, 5. 

20 American Journal of Public Health. October 1996.

Research Designs: 

Gender

BACKGROUND

With the founding of the Office of Research

on Women’s Health and the enacting of

the mandate that women and minorities

be included in clinical studies, the National Institutes

of Health (NIH) has responded to the issues raised

about gender in medical research. The Food and Drug

Administration (FDA) has echoed this concern about

gender in medical research by changing its policy on

the study and evaluation of drugs in women. These

policy changes by NIH and FDA reflect the growing

concern for women’s health, and have also opened the

door to other issues regarding clinical studies, gender

differences, and new approaches to medical studies.

CLINICAL STUDIES

Designing Clinical Studies

NIH guidelines are still evolving; many in the

medical community view them as a starting point 

in the discussion of gender and clinical studies. For

example, the issues mentioned by the working group

included the implications of the semantics of the NIH

guidelines on “inclusion” of women and minorities in

clinical studies. That women and minorities should 

be included suggests that it is appropriate to design a

study with men as the major focus as long as women

are included. This concept should be addressed more

clearly to promote studies that are initially designed 

for women or minorities. The point is not to merely

increase the number of women in clinical trials, or

even how to determine if they are eligible for trials, 

but rather what is being studied, the nature of how 

the experimental groups are being determined, and

how drugs and devices are being tested. The design 

of the research study must derive from the questions

being asked. Designs will differ for the questions 

being asked, for example, whether there is a difference between men and women in response to a drug

and whether the drug works in women. Even when

women are included in clinical trials, the data may 

be aggregated in such a way that investigators 

analyze the data overall and not by sex.

Many researchers have noted that politics can 

prevent or hinder the study of sexual differences 

in clinical trials. For example, until recently, it was 

difficult to publish a paper with the words “sex differences.” The paucity of studies on neuroendocrine

aspects of female functions may be attributable to a

belief that it was not politically correct to acknowledge

different functioning at different times of the month or

to a fear of discrimination based on the differences.

Socioeconomic factors applicable to women can

complicate research design. Socioeconomic differences

cannot be measured in the same way in men and

women because there are no good gender neutral 

measures of socioeconomic status. Three basic measures of socioeconomic status are income, occupation,

and education. These factors tend to correlate better 

in men than in women. Women can be highly educated and have a low household income, and be 

in a pink-collar job.

Cochairs

George W. Counts, M.D.

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Otis Brawley, M.D.

National Cancer Institute

National Institutes of Health

Rosalie Sagraves, Pharm.D.

University of Illinois at Chicago

Rapporteur: Carollyne Hutter

97

VOLUME 4
98

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Finally, there is a lack of studies on healthy people,

an area for which research designs must be unique to

healthy women. For example, the effects of the menstrual cycle on drugs and other therapies should be

analyzed in clinical trials.

Although incorporating women into the designs 

of clinical studies may create logistical issues, it may

result in new areas of research, innovative research

designs, and cost-effective options. A well-designed

and well-conducted study involving women and

minorities can provide information about treatment 

and care of direct benefit to men and women alike. 

In addition, results from such studies can enable 

policymakers to make decisions that will improve 

the overall health of the nation.

Balancing Research Cost While Asking Clinically 

Significant Questions

Adding gender issues to a biomedical study 

can considerably increase study costs, at a time when

pharmaceutical companies and grant agencies are cutting costs. “All of our costs in industry have been cut,

are being cut, and will be cut in the future. What this

means is that any increase in cost in any area of drug

development will be carefully considered.”1 Although

the inclusion of women as research subjects may initially cost more, the savings will be realized in the

longer term. Excluding women from trials would 

result in inadequate data, which could lead to 

inappropriate treatment, added risks for women, 

and increased costs to society.

How can costs in clinical trials be kept at a minimum and still have women participate? One possibility

is for investigators to do multi-institutional, collaborative studies. Another possibility is for investigators to

ask smaller questions and be willing to be patient to

get meaningful answers. The focus of research should

be on clinically significant questions, the answers to

which will change how health care providers take care 

of their patients, whether women or men. The medical

research community is currently examining the role 

of managed care organizations (MCOs) in women’s

health research. Because large numbers of people use

the services of MCOs, there is an extensive pool of data

potentially available to researchers. However, the role

of MCOs in women’s health research is more extensive

than just as a data source — MCOs could significantly

affect clinical research in general.2 At the Society for

the Advancement of Women’s Health Research Annual

Corporate Advisory Council Conference in 1996, attendees generally agreed that MCOs could have a negative

effect on traditional clinical efficacy research because 

of financial, political, and operational concerns. These

concerns require that knowledge be practical and that

practicality be incorporated into research design, costs,

measurement, and potential application.3 MCOs that

perceive research as increasing costs, rather than generating profits, have been reluctant to become involved

in research.4 The trend of MCOs and women’s health

research is “improved processes for providing care, 

but reduced technologies for implementing cures. The

challenge for the research advocacy community will 

be to ensure the former without sacrificing the latter.”5

Recruiting and Retaining Women in Clinical Trials

Unless the appropriate women, in sufficient numbers, participate in clinical trials, the base of biomedical

knowledge about specific conditions and diseases will

always have major gaps. For example, generally women

do not use the health care system for menopause,

unless they need a hysterectomy. This absence creates

difficulties for capturing an accurate picture of women

and menopause, and is one of numerous barriers to

addressing the health issues of women: “Access to

health care, mistrust of the medical system, language

barriers, cultural beliefs, and even transportation and

child care are all issues that must be addressed to

ensure that women are able and willing to participate in clinical studies.”6

Designing research models to include women 

in clinical studies presents new questions about how 

to recruit women. The recruitment techniques that 

are used for men may not be effective for women. 
99

VOLUME 4

On some occasions, when pharmaceutical companies

opened trials to women, they did not come forward to

participate. In such cases, investigators may be inclined

to assume that women do not wish to participate and

may wish to proceed with the trial as before. Thus,

there is a need to train investigators to use different strategies to increase women’s participation. For example,

typically the first step in recruiting potential participants is to advertise in newspapers. Whereas newspaper advertisements may be effective in recruiting men,

studies indicate that women are more likely to respond

to radio messages or television advertisements. In

recruiting women for some AIDS trials, investigators

found that they had to offer incentives, such as transportation and day care, to enable women to participate.

Informing the appropriate people is key to recruiting for clinical trials, and yet two major considerations

are often overlooked. One, although physicians’ referrals

can be crucial to successful recruitment, many physicians are not informed about clinical trials. Two, if the

potential population to be recruited includes women

whose native language is not English, the recruitment

plan should include disseminating information in 

languages other than English.7

Once informed about a study, whether or not

women decide to participate may depend on their attitudes toward the medical profession, research team

members, and clinical studies in general. Participants’

confidence in those conducting the research, and even

their opinions about the quality of study design, can 

be important determinants of enrollment and retention.

The recruitment and implementation plans should take

into consideration establishing one-on-one relationships

between research staff and study participants, having 

as many women as possible be members of the clinical

staff, encouraging joint decisionmaking and informed

consent, and establishing educational and support 

networks of former and current study participants.8

The relation between the research institution 

and the community participating in the study should 

be considered when recruiting participants. Clinical

studies may fail if the researchers and community do

not have common goals or a shared recognition of the

needs of the community. Trust should be established

between the research institution and the community,

along with a partnership approach. Partnerships can 

be established by having members of broad-based

groups, such as religious groups, participate as early 

as possible in the recruitment process, preferably at 

the planning stage. Partnerships that create strong personal relationships between participants and clinical

staff can lead to such benefits as higher participant

retention and compliance with study protocols: “An

attitude of caring and assistance on the part of investigators and staff may keep participants returning to 

the facility not only to participate in the study, but 

also for the personal and social contacts.”9

When recruiting and retaining women in clinical trials, investigators need to consider all the abovementioned concerns, but these concerns should not 

be viewed as absolute obstacles to having women 

participate in studies — the obstacles can be overcome with careful planning and persistent efforts.

Ethical and Liability Considerations

A major ethical and liability consideration is 

the inclusion of women of childbearing age in clinical trials. In particular, pharmaceutical manufacturers

worry that including women of childbearing potential

in clinical trials can make manufacturers vulnerable 

to lawsuits. NIH and FDA guidelines address this 

issue. In 1993, FDA reversed its recommendation that

women of childbearing potential be restricted from 

participating in drug trials. FDA issued new guidelines

about including both genders in drug development,

analyzing clinical data by gender, assessing potential

pharmacokinetic and pharmacodynamic differences

between genders, and conducting specific studies in

women. It should be noted that excluding women 

does not exempt manufacturers from liability risks; 

the manufacturers are still responsible for knowing 

how pharmaceutical agents affect women.
100

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Scientists, pharmaceutical companies, and FDA

emphasize the problems of testing pharmaceutical

agents in pregnant women. They are concerned about

protecting fetuses from potential toxic therapies as 

well as the possibility of liability and law suits. 

During pregnancy, physiological changes occur in

the cardiovascular, renal, gastrointestinal, pulmonary,

and hepatic systems. These changes can affect how a

drug is absorbed, distributed, metabolized, and eliminated. According to a white paper by the American

College of Clinical Pharmacy, pregnancy significantly

influences the pharmacokinetics, and possibly pharmacodynamics, of various compounds.10 The fetus and

placenta should be regarded as different compartments

in the pharmacokinetic model in pregnant women.

Although pregnant women have been excluded

from clinical trials in the past, they use drugs during

pregnancy. Companies have marketed drugs used by

pregnant women without having knowledge about 

the maternal and fetal effects of the drugs. An Institute of Medicine report states that 75 percent of pregnant women use prescription and over-the-counter

medications.11 In 1992, investigators discovered 

that pregnant women with hypertension who used

angiotensin-converting-enzyme inhibitors during the

second and third trimesters sometimes experienced

fatal neonatal renal problems.12

FDA is examining the issues of having pregnant

women participate in clinical trials of new drugs and

biological agents. The agency has acknowledged the

importance of including pregnant women in trials that

use experimental therapies for life-threatening conditions, such as new therapies for AIDS. New models 

are needed, including animal models, and followup

procedures, such as postmarket surveillance for drugs.

Animal Studies

Research on animals can lay the foundation of

progress toward developing research designs for clinical trials, yet female animals are generally not used 

in research because of the rate and complexity of the

estrous cycle. Few animal models mimic the menstrual

cycle and when they are used it is almost exclusively

for contraceptive research. Otherwise, if a study uses

female animals, the animals are basically “castrated”

before being studied. Investigators should investigate

the use of female as well as male animals and differences in the hormonal milieus in these animals and

consider looking at several animal models, not just 

a rodent model.

GENDER DIFFERENCES

Women and men are obviously different in regard 

to the presence of hormones, such as testosterone,

estrogen, progesterone, and prolactin. Since these 

hormones affect gender-dependent physiological characteristics, they may also modify the pharmacokinetics

and pharmacodynamics of selected drugs. Yet, the scientific knowledge base does not provide information

about gender differences in responses to drugs. It is

vital that investigators determine under what conditions gender differences happen and design clinical

studies appropriately to examine these situations.

Women and men also differ biologically in body

composition, size, and metabolism. These factors may

influence the dosage, disposition, and metabolism of

drugs. Therefore, when determining drug dosing it

may be appropriate to consider these differences, 

especially body size and composition, instead of 

using standard fixed doses.

The way diagnostic technology and medical

devices are designed poses concerns. Most medical

diagnostic technology is built with a man in mind; and,

because some medical devices are designed for men,

women are often too small for the use of the devices.

Differences between women and men are more

than just biological. There are also behavioral and psychosocial differences between the sexes. Differences in

lifestyles, such as exercising, alcohol consumption, and

cigarette smoking, affect health. Women and men perform different roles in society, which influence their
101

VOLUME 4

health. Women are more often the victims of domestic

violence and have higher rates of depression and 

eating disorders.

Another important gender issue is aging. On 

average, women live 7 years longer than men; they

constitute the majority of the population over 65.13

Therefore, research on the aging process should 

include women. Women and men are affected by different diseases and conditions. Rheumatoid arthritis

and osteoporosis are more common among women

than men; whereas, more men than women suffer from

gout. In addition, older women tend to experience

more adverse reactions to medications than men.14

In 1994, the Institute of Medicine Committee on

the Ethical and Legal Issues Relating to the Inclusion 

of Women in Clinical Studies concluded that gender

differences are relevant to how clinical drug trials are

designed. They summarized that “differences in size, 

fat ratios, and metabolic rates are associated with differences in drug concentration, metabolism, and

response. Psychosocial differences are associated with

differences in risk factors and, more important, in

adherence to experimental protocols. These differences can change over time, both in the short term

(during menstrual cycle) and the long term (with 

pregnancy, lactation, and aging).”15

LONGITUDINAL AND

LIFE PHASE RESEARCH

Because of the unique role that female hormones

play in women’s lives, women go through various

stages based on hormone support. These stages influence the development of diseases such as myocardial

infarction and osteoporosis. Thus, a study in which

only premenopausal women participate may not reveal

findings that are applicable to postmenopausal women.

If women participate in pharmacokinetic and pharmacodynamic studies, it is vital to establish whether they

are premenopausal or postmenopausal and whether

they are receiving hormone replacement therapy 

or oral contraceptives.

It is essential to conduct studies that include and

describe the different phases of a woman’s life, and to

classify women by the menopausal stage, instead of by

age only. This was not done in breast cancer screening

trials. In these trials, women were grouped by age,

instead of by pre- or postmenopausal status.

Research designs and study instruments should 

be developed that describe the menstrual cycle longitudinally and assess hormone differences across menstrual cycles. Clinical trials that include premenopausal

women should study changes not only month to

month, but also week to week, plotting information

over two or three menstrual cycles. A single blood level

is not particularly helpful, because it represents a single

point in time, instead of a view of dynamic change.

New technologies may be needed to perform studies:

instead of blood measurements, investigators should

explore using less intrusive measures in populationbased studies, such as saliva and urine samples.

INSTITUTIONAL REVIEW

BOARD SHOPPING

Before conducting research, some pharmaceutical companies go “institutional review board (IRB)

shopping,” looking for the appropriate IRB for the

investigation. IRBs may find equitable selection criteria

confusing if the private and public sectors present 

conflicting policies. Sometimes IRBs get requests from

pharmaceutical companies to do research that specifically excludes women. When an IRB questions a protocol or tells a pharmaceutical company to change the

protocol to allow women in the studies, the company

may threaten to take their studies elsewhere. Money for

research is at such a premium that if a pharmaceutical

company has any conflict with an IRB, the company

can move the study elsewhere.

To deal with IRB shopping, IRB chairs have proposed establishing a network of IRBs so that IRBs can

communicate with each other and be aware of pharmaceutical companies’ studies and activities. Another way
102

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

to avoid IRB shopping is to have pharmaceutical companies contribute to a pool of funds (perhaps managed

by NIH), which would separate research money from

pharmaceutical companies’ perspectives. Such a pool

could also be established with funding from MCOs.

Another concern with IRBs is that the boards 

do not learn about the population composition of the

study until the annual or interim project review, which

restricts an IRB’s capability to secure a balanced population study. Involving IRBs in the early design phases

of research would help to ensure that there is an equitable representation of study subjects.16

IN SEARCH OF A 

NEW PARADIGM

In 1995, Gerhard Levy wrote about patientoriented pharmaceutical research that focuses on the

individual. This research would extend beyond pharmacokinetics, pharmacodynamics, and medication

adherence to include the behavioral sciences.17 In a

similar vein, the World Health Organization’s Tropical

Diseases Research Program uses a multidisciplinary

approach that views women’s health as a result of

sociocultural interactions and economics.18 A framework for health research is supported that would 

create a gender framework that incorporates research

from such diverse fields as medicine, pharmacy, public health, epidemiology, anthropology, economics,

entomology, agriculture, environmental engineering,

ecology, and health education. In this approach, women

and men are seen as principal agents of their own

health, with personal needs, priorities, and preferences.

EDUCATION

The issues discussed above all require education.

The general public needs to learn more about women’s

research issues and about participating in clinical trials;

pharmaceutical companies about inclusion of women

in trials; and investigators about how to design trials

for women’s participation and how to create new research models based on women. Moreover, society, 

the medical establishment, and investigators should 

be educated on the importance of having more 

women investigators.

CONCLUSION

Scientists will continue to struggle with the fact

that they serve a diverse society — diverse in sex, size,

age, culture, and income. The population is not only

diverse, but dynamic. Given the nature of society, it is

vital to recruit, retain, and observe diverse populations

in an ethical manner. The public needs to be informed

and educated about medical studies and their importance. Ultimately, scientists must search for the most

significant findings, those that will affect the practice 

of medicine. Part of science’s responsibility is to serve

all; yet, science must also focus on the most meaningful issues, and not be diverted by simplistic 

academic issues.

References

1 Bush, J. September 1994. The industry perspective 

on the inclusion of women in clinical trials. Acad 

Med 69:712.

2 Moore, D. and Bernard, S. 1996. The impact 

of managed care on women’s health research. 

J Women’s Health 5:197–202.

3 Ibid., 198.

4 Ibid., 201.

5 Ibid., 202.

6 Kaufman, B. and Rodriguez-Trias, H. 1995. Participant

and community issues in the recruitment and retention

of women in clinical studies. In Recruitment and Retention of Women in Clinical Studies. Office of Research on

Women’s Health, National Institutes of Health, p. 17. 

7 Ibid., 19.

8 Ibid., 18.

9 Kuller, L.H. 1995. Current experiences in women’s health

research. In Recruitment and Retention of Women in Clinical

Studies. Office of Research on Women’s Health, National

Institutes of Health, p. 27. 

10 Sagraves, R., et. al. 1993. American College of Clinical

Pharmacy White Paper. Women as research subjects.

Pharmacotherapy 13:534–42.
103

VOLUME 4

11 Mastrianni, A., Faden, R., and Federman, D. (eds.). 

1994. Women and Health Research: Ethical and Legal Issues 

of Including Women in Clinical Studies. Washington, D.C.:

National Academy Press, p. 93.

12 Merkatz, R., et al. 1993. Women in clinical trials of 

new drugs. New Engl J Med 329:295.

13 Mastrianni, A., Faden, R., and Federman, D. (eds.).

Women and health research, p. 93.

14 Ibid.

15 Ibid.

16 Henderson, M. and Lee, M.M. 1995. Investigator and

institutional issues in the recruitment and retention of

women in clinical studies. In Recruitment and Retention of

Women in Clinical Studies. Office of Research on Women’s

Health, National Institutes of Health, pp. 11, 14.

17 Levy, G. 1995. Patient-oriented pharmaceutical research:

focus on the individual. Pharm Res 12:943–44.

18 Rathegeber, E. and Vlassoff, C. 1993. Gender and tropical

diseases: a new approach. Soc Sci Med 37:513–20.

Health Impact and

Health Outcomes:

Advances in 

Biotechnology

How can advances in biotechnology be incorporated

into clinical care and health professional education programs for women’s health, including prevention, screening,

and treatment? What is the role of gender in access to 

care, diagnostic and therapeutic interventions, and patientprovider communication? What are the ethical, legal, 

and social issues? How can the diverse community 

of women benefit from state-of-the-art research?

INTRODUCTION

Avaccine offering protection against serious 

illness, an effective drug treatment for HIV/

AIDS patients, a diagnostic test capable of

detecting a treatable disease at its earliest stage, and

artificial joint replacement devices: these are examples 

of the biotechnological advances that offer immeasurable benefits for the health and quality of life of all

Americans. But as these “miracles of modern science” 

are developed, important gender-related questions

must be asked: Are the side effects of a vaccine the

same for men and women? Do men and women 

react the same way to new HIV/AIDS drugs? Are 

the biotechnology applications that have become 

standard clinical care appropriate and advisable for

women? Should artificial joint devices be designed 

differently for male and female patients? The answers 

to these questions are the essence of this discussion

because, in fact, many biotechnological advances 

are put into common use without regard to genderspecific considerations. 

Biotechnological advances are the result of a

lengthy process that most often begins as a new idea 

or concept in the laboratory, continues through various

clinical research stages, seeks approval for clinical care

applications, and ultimately reaches the marketplace

and the consumer. The extent to which this process

takes into account gender-specific considerations has

important ramifications for women’s health. It is important not only to look at new advances but also to

consider existing or older technologies that may not 

be considered in gender terms, that is, technologies

that are gender-neutral, and possibly not advantageous 

to women. The recommendations presented in this

report are intended to integrate and focus attention 

on women’s health concerns so that biotechnological

advances benefit all segments of the population.

BIOTECHNOLOGIES:

CONCEPT TO 

MARKETPLACE

Technology transfer has been defined by the

National Institutes of Health (NIH) as “the process 

by which the fundamental discoveries of laboratories

are brought forth into practical knowledge and useful

products for the benefit of humanity.” The Federal 

Government, particularly the Public Health Service,

including the Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and

the National Institutes of Health and its grantee institutions, plays a major role in biotechnology transfer.

Cochairs

Judy Norsigian

Boston Women’s Health Book Collective 

Maria Freire, Ph.D.

Office of Technology Transfer

National Institutes of Health

Rapporteur: Debra Powell

105

VOLUME 4
106

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

The Bayh-Dole Act of 1982 and the Federal Technology

Transfer Act of 1986 encourage greater interactions

between the Federal Government and universities,

foundations, and industry through cooperative research

and development agreements and through the licensing

of patented inventions developed by public health

agencies or by researchers at universities and notfor-profit institutions funded by NIH. 

Mechanisms for technology assessment to determine safety and effectiveness are evolving. Traditional

methods, based on peer review, are being transformed

by information technology that makes dissemination 

of research findings more immediate and eliminates 

filters. The criteria for such assessments are open for

debate. Although “safety and effectiveness” are important principles, many people — practitioners and consumers alike — hold different concepts of what these

terms mean. Disagreements persist about what level of

risk to the individual is acceptable, even in the face of

substantial public health benefits to society as a whole.

Is it appropriate to demand both the latest technology

— whether adequately assessed or not — as well as 

the right to “sue” if there is a problem? Who should

determine what level of safety and effectiveness is 

sufficient? An expanded public discourse on these 

matters is sorely needed. 

There is also a need to recognize the practical 

business and economic implications of new product

development. Traditionally, companies have looked at

new technologies and asked how they could make a

profit; some companies are now looking at unmet needs

and considering how to respond in a profitable way. 

BIOTECHNOLOGIES:

OPPORTUNITIES AND

RECOMMENDATIONS

The recommendations that follow are presented 

in four broad categories: (1) technology transfer and

assessment, (2) patient care, (3) clinical trials and 

FDA approval, and (4) communication and outreach.

Technology Transfer and Technology Assessment

The process of moving biotechnological inventions

and advancements from basic research to clinical testing to the marketplace inherently provides opportunities to consider and meet the unique needs of women.

Any new drug, vaccine, device, or diagnostic tool must

be methodically assessed as it moves from the laboratory to safe, efficacious clinical applications in women. 

The technology’s commercial viability must also be

appraised and confirmed before it is introduced as 

a new product.

The commercial introduction of a new product 

or procedure, however, is not the end of the process.

Even after a technology has been introduced to the

marketplace, there is a need for continual assessment

to ensure that the product remains safe and efficacious

and does not become obsolete. Prenatal ultrasound

testing provides one example of the need for such

assessment. The National Institute of Child Health 

and Human Development, along with the NIH Office 

of Medical Applications of Research, sponsored a 

workshop titled “Ultrasound Screening: Implications 

of RADIUS (Routine Antenatal Diagnostic Imaging

Ultrasound Study).” RADIUS, a large, randomized 

clinical trial, assessed the effectiveness of routine 

ultrasound screening for pregnant women at low 

risk for poor pregnancy outcomes. Although the 

study results indicated no real medical value of ultrasound for this population, practitioners have continued to use the technology. This is an example of an

adaption of a technology from an original application

in high-risk situations to an entirely different application, the efficacy and cost effectiveness of which 

may be questionable. 

The following recommendations encourage a 

more deliberate assessment of new biotechnologies as

they affect women and call for ongoing assessments

that consider women’s health perspectives:

• collaborate with technology transfer programs to

identify and evaluate technologies that warrant further research based upon the ORWH agenda; and
107

VOLUME 4

• assess, in a systematic way, which technologies 

are obsolete and/or used inappropriately.

Clinical Trials and FDA Approval Process

Clinical trials are designed to establish a level 

of safety and efficacy prior to the development and

marketing of a drug, device, or treatment. Usually

undertaken as a three-phase activity, clinical trials may

be sponsored and funded by the Federal Government

and for private industry. Participation in clinical trials is

voluntary and offers individuals who meet the specific

medical criteria access to promising drugs, devices, and

treatments long before they are approved for general

use. Institutional Review Boards seek to protect participants’ rights and safety by ensuring minimal risk

through careful research design, appropriate recruitment strategies, and thorough informed consent 

procedures. Participants should also be provided 

medical care throughout the investigation. 

As for all medical technologies, clinical trials 

are a key stage in the introduction of biotechnology

products and raise many crucial overarching questions. For example, how can research designs be

changed to encourage greater involvement by women

(i.e., clinical trial participation)? Which populations 

of women are not now participating in trials? Can 

new kinds of trials be designed? Is it possible to 

design sound prospective studies? What ethical 

and social issues are involved? When is participation truly in the best interest of the individual?

Ensuring diversity and pluralism is part of the

challenge. The involvement of communities in research

design, implementation, and recruitment must be

encouraged. The HIV/AIDS and breast cancer activist

communities have been heavily involved in the clinical

trials process in those disease areas, for example.

In addition to questions regarding research 

designs and recruitment, there are questions about

what constitutes “safe and efficacious” drugs, devices,

and treatments, and about what level of approval 

regulation is needed. FDA regulates medical devices

based on their degree of risk to the public. Devices 

that are life supporting, life sustaining, or implanted

must receive agency approval before they can be 

marketed. But what level of certainty should be

required? What are appropriate end points? The

approval process should take into account the 

range of societal values on these issues.

Another concern relates to the need for postmarket assessments to identify standard practices 

that may no longer be medically desirable or advisable, and to identify low-level effects not initially 

evident. The FDA continues to collect and analyze

reports on approved drugs and devices to monitor 

for any unexpected adverse reactions. 

There is general agreement that there is a need 

for systematic dissemination of clinical trials results.

Building on a congressional mandate to create a clinical

trials registry for women’s health, the NIH’s Office of

Medical Applications Research, the Office of Research

on Women’s Health, and the National Library of Medicine are working to assemble a database of trials that is

relevant not only to women’s health but also across the

spectrum of research. Such a registry would contribute

to a health care system in which evidence from clinical

trials can be more rapidly incorporated into clinical

practice. A systematic means of archiving and retrieving the experience of previous and ongoing research is

central to the timely and ethical use of therapies and

health resources. The Cochrane Collaboration is an

example of such an effort on an international scale.

Research on biotechnology applications in the 

area of prevention also deserve greater attention. Traditionally, prevention has been underfunded relative 

to other categories of research. Two such areas that

have and will continue to have a major impact on

women’s health are contraception and prevention 

of sexually transmitted diseases.

The clinical trial/approval process presents opportunities both for increasing the participation of women

in study designs and for seeking a balance in research
108

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

agendas. Recommendations to improve the process

include the following:

• participate in efforts to improve the quality of 

study design, data collection, and analysis; and

• advocate for a better balance of research among

preventive, diagnostic, and treatment initiatives.

Patient Care

The cost effectiveness of treatment, particularly 

in managed care environments, is becoming an essential part of choices in clinical care. But the question

remains: When are technologies advanced enough to

gain status for third-party reimbursement? Even in a

climate of cost containment, physicians in managed

care, specialists, and primary care physicians must be

held to certain standards of care. Improvements in the

education of health care practitioners and changes in

clinical care practices are essential. In addition, the

insurance industry should be included in the education process that addresses new and emerging 

applications of biotechnology. 

Clinical practice guidelines, which recommend

appropriate practices based on routinely available technologies and clinical experience, should incorporate

gender as a variable. There is need to define quality

and outcome measures that are broader and more sensitive to women’s needs and better measures of quality 

of care. To illustrate, a manufacturer of a hip replacement device refused to make a device that would be

compatible with the female anatomy despite problems

that women were experiencing with the hip replacement device because of its large size. The issue is not

just developing new technologies, but also refining

technologies and practices from a gender perspective,

particularly in managed care settings.

The NIH Consensus Development Program is a

significant health technology assessment and transfer

program. A consensus statement evaluates state-ofthe-art scientific information on a given biomedical

technology with the purpose of resolving a particular

controversial issue in clinical practice. Statements

answer a series of questions concerning efficacy, risk,

and clinical applications and recommend future use.

However, the effect of the Consensus Development 

Program on clinical practice is unclear, since there are

various nonmedical factors involved. The program has,

however, had measured success in influencing reimbursement policy and specialty organization policy,

thereby indirectly affecting physician behavior. The

Consensus Development Program offers one avenue 

for implementing the following recommendations:

• involve a broad constituency in developing 

professional practice guidelines that have sexand gender-specific components;

• identify quality and outcome measures that are

broader and more sensitive to women’s diverse

needs; and

• propose improvements to existing technologies

based on new information on gender differences.

Communication and Outreach

On matters pertaining to new biotechnology developments, communication and outreach to health care

providers, professionals, and the public remain an

enormous challenge. What are the best ways to disseminate information on biotechnology advances both

before and after they reach the marketplace? How can

practitioners keep informed and current on the range

and volume of developments in biotechnology? In

addition, the translation of technical information into 

lay terms must accommodate the needs of different

audiences. The role of the media in this process is 

also a factor. How do you create responsible media?

Identifying mechanisms by which new biotechnology advances may be integrated into the education

process for practitioners is critical. For example, how

can state-of-the-science information on such complex

and dynamic topics as genetics be incorporated into

medical school instruction? Epidemiologic and biostatistical training and education are also lacking despite

the fact that these skills are fundamental to medical,

nursing, and other disciplines. 
109

VOLUME 4

Seeking input from diverse populations regarding their most pressing needs should be an ongoing

process. How can we ensure that the interests of those

outside the scientific and business worlds are served?

For example, HIV/AIDS and breast cancer advocates

represent a new level of involvement by nonscientific

communities. How can meaningful forums be developed for the exchange of information between and

among scientists and nonscientists?

Recommendations to improve these channels 

of communication are as follows:

• continue to sponsor dialogs among clinicians, 

scientists, advocacy groups, managed care providers, insurers, and other parties to improve 

overall communication on such topics as values,

concepts of safety and efficacy, and consequences 

for both the individual and society;

• continue to seek input from diverse populations 

of women regarding their most pressing health

needs and concerns to ensure their inclusion 

in the research agenda; and

• work with health professions educators to integrate

gender-based science into the curriculum.

Preventive 

Interventions:

Addressing Gender

Differences

INTRODUCTION

Preventive interventions for specific syndromes,

diseases, or behaviors are typically developed

through a series of steps. Each step builds 

on its predecessor and supports its successor. The

sequence, as described in a report of the National

Academy of Sciences, consists of seven steps: (1) recognizing and defining the syndrome, disease, or behavior

to target; (2) delineating the risk factors involved; 

(3) conducting studies to identify relatively powerful

and malleable risk factors and protective factors, individually and in combination; (4) developing and 

testing a variety of approaches to decrease risk and 

increase protection; (5) conducting field trials to assess

the most efficacious and promising interventions; 

(6) implementing and evaluating the intervention in 

community settings, and assessing its effectiveness 

for the target population, sometimes at multiple sites;

and (7) transferring knowledge gained by the intervention programs to the public domain as widely 

and rapidly as possible.1

Whereas the developmental sequence for preventive interventions may sometimes be the same for

women and men, the nature of interventions designed 

for women, and the techniques for studying them, 

may require approaches that are different from those

based on models of men’s health and behavior (particularly in steps 1 through 4). Preventive interventions for

women should take into account the special attitudes

and values women tend to live by. Women feel social

and financial pressures to care for others as much as, 

if not more than, they care for themselves.2,3 Many

women do not believe that self care is valid or is a

highly prized facet of one’s identity; their socialization

too often promotes caring for others over caring for

oneself in the physical, mental, and spiritual domains 

of life.2,4 This issue varies in significance across ethnic

minority groups. If women do not value self care, their

attempts to adopt and continue preventive health measures are less likely to succeed. Basic self-caring behaviors, such as a healthy diet and adequate exercise, are

critical not only for immediate health gains, but also 

to reduce the risk of disease in later life (e.g., heart 

disease and osteoporosis).5

PROGRESS AND GAPS 

IN KNOWLEDGE 

Appropriateness to Life Transitions

One effective way of promoting good health 

practices among those at risk is to target preventive

interventions at life transition points.6 Examples of 

successful intervention programs aimed at particular

life transitions include Early Intervention for Preterm

Infants;7 the Perry Preschool Program;8 the Community Epidemiological Preventive Intervention: Mastery

Learning and Good Behavior Game (first graders’ adaption to school);9 the Family Bereavement Program (for

children surviving the death of a parent);10 the Positive

Cochairs

Jane Pearson, Ph.D.

National Institute of Mental Health

National Institutes of Health

Marilyn Gaston, M.D.

Health Resources and Services Administration

Phyllis Greenberger, M.S.W.

Society for the Advancement of Women’s Health Research

Rapporteur: Mary E. Cadette

111

VOLUME 4
112

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Youth Development (social competence for adolescents);11 the Prevention and Relationship Enhancement Program (for couples in marital distress);12 the

Prenatal/Early Infancy Project (enhancing personal

development of new mothers);13 the JOBS Project 

for the Unemployed;14 Comprehensive Support for

Caregivers of Alzheimer’s Disease Patients;15 and the

Widow-to-Widow Program: A Mutual Help Program

for the Widowed.16 Most of these programs are directed

to men and women alike. However, a number of early

intervention programs focus on women who are new

mothers, or mothers of young children, both as targets

of interventions and as “deliverers” of interventions 

to their children. Also, many available interventions

focus on women who, during late adulthood, become

widows or care givers for a dependent spouse.

Followup studies of a number of intervention programs for infants and toddlers have shown continuing

positive benefits.17 However, no one intervention, at

any one time, is likely to accomplish the comprehensive goals of sustained disease prevention and health

promotion for a lifetime. “Booster” interventions that

take place at time-defined intervals or at transitiondefined events (for example, the birth of a second

child) may therefore be necessary. Interventions,

including the promotion of certain values and norms,

that support individual change through multiple 

levels of community structures may be more likely 

to effect desired behavioral changes than interventions focusing only on individuals.

There is an unfortunate lack of prevention 

research programs designed for the needs of many

adults, such as middle-aged women or elderly men.

Likewise, limited attention has been paid to risk factors that can occur across generations in the same 

family. The research design of prevention programs to

reduce risks are beginning to evaluate outcomes and

compare benefits and costs across generations within 

a household.18 For example, interventions focused 

on helping an adult, child, or spouse care for a dependent parent within the household should consider 

the costs and benefits to both the care provider 

and the dependent parent.19,20

Cultural Relevance of Interventions

Advances in research on women’s health will not 

be effectively available to women of all ages unless 

the inequities of access to health care that arise from

poverty, racism, homophobia, and ageism are considered. These inequities are related to practical barriers,

such as cost and distance, as well as to cultural factors. 

A crosscutting issue in applications of research

advances for health promotion is the double need to

see that programs are designed to be culturally relevant 

to the targeted population and that researchers and

practitioners be culturally competent with the specific

population they are serving. “Cultural relevance” refers

not only to ethnicity but also to the cultures of the

inner-city poor, lesbians, older women, and of migrant,

homeless, and rural women. “Cultural competence”

refers to a person’s ability to be sensitive to the attitudes, values, beliefs, practices, and desired outcomes

of the cultural groups with whom one is working, as 

a matter of good science, therapeutic effectiveness, and

professional ethics.21–23 If beliefs and attitudes of certain cultures are maladaptive, developing programs 

to change them may be most efficacious if they begin 

with a good understanding of current beliefs or values.

For example, a researcher working with an aging population must realize that many older women respect

physicians deeply and will rarely question a doctor’s

recommendations or ask for information about alternative treatments. Certain cultures have evolved unique

beliefs about the causes of specific diseases; for example, Dressler has described the differences between the

beliefs of African-American women about the causes 

of hypertension and conventional models.24 Different

cultures also vary in the degree to which their members

can comfortably discuss sexual behavior;25 thus, programs designed to prevent sexually transmitted diseases

must offer several levels of discussion to avoid insulting

the intended audience and reducing participation.
113

VOLUME 4

Many effective preventive interventions include peerprovided counseling and peer supports, which promotes the community’s values in health behaviors and

lends credibility to the intervention.26 Cultural competence is achieved through personal experience, typically

by immersion in the field of treatment or research,

which leads to the mastery of the skills necessary to

develop or deliver preventive interventions.27,28

The degree to which prevention programs involve

ethnic minorities varies as a function of the degree to

which efforts are made to reach complete samples of

those at risk. Samples drawn from county death records,

unemployment records, or school registrations, for

example, will be more representative of a population

than samples drawn up in other ways. Programs whose

participants are recruited through participants’ selfidentification or clinical referrals tend to have a 

nonrepresentative sample.29

Overall, the availability of prevention programs

designed for women of ethnic or minority groups

known to be at risk is not proportionate to their needs.

Women known to be at high risk for certain health

problems include Native American adolescents and

adults for substance abuse, Hispanic and AfricanAmerican women for diabetes, and African-American

women for hypertension.30 Few studies have included

sufficient members of any ethnic or cultural minority 

to accommodate assessment of the variation within the

ethnic or cultural group. Among lesbians, for example,

random samples are difficult to obtain. White, middleclass lesbians tend to be overrepresented in study samples, and actual disease prevalence among lesbians as 

a whole is unknown.31 Knowledge of within-group 

differences is as important as knowledge of crosscultural differences as a basis for understanding 

health behaviors.32

Scope of Interventions: Comorbidity

Prevention efforts must increasingly recognize 

that physical health and mental health are not separate

entities. Posttraumatic stress disorder, often associated

with sexual abuse, is a common precursor of irritable

bowel syndrome and other gastroenterological problems.33 Rates of depression are highest among women34

and among persons who experience acute or chronic

physical disorders.35 Rates of depression are also high

among persons who have illnesses that predominately

affect women, such as multiple sclerosis,36 myasthenia

gravis,37 and chronic fatigue syndrome.38 Women of

ethnic minorities may be especially at risk for undetected (and untreated) depression, with negative physical and mental health consequences.39 Homeless

women have twice the prevalence of major depression

than the general population.40 Migrant and seasonal

women farm workers are at risk for psychosocial distress because of their lifestyle.41,42 Clinical depression

often can be effectively treated,43 and its successful and

continued treatment can limit morbidity and mortality. This has been demonstrated, for example, among

women with cancer 44,45 and among frail nursing 

home residents, the majority of whom are women.46

RECOMMENDATIONS

The working group made the following 

recommendations:

General Recommendations

• Encourage ORWH to promote further 

cross-agency prevention initiatives with relevance for women’s health, such as the recent 

violence prevention efforts by the National Institutes of Health (NIH), Centers for Disease Control

and Prevention (CDC), and the Health Resources

and Services Administration (HRSA); and

• Encourage ORWH to collaborate with 

the NIH Prevention Consortium to review 

portfolios and consider needed initiatives on 

understudied populations of women (e.g., 

women with disabilities, migrant women 

farm workers, and homeless women).
114

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Specific Recommendations

• Encourage ORWH to sponsor requests for application on violence prevention, with cross-agency

coordination by NIH, CDC, and HRSA;

• Expand the Women’s Health Initiative 

to include more research questions on 

preventive interventions;

• Identify and replicate models that work: 

annual HRSA competition to find innovative, 

creative community-based models;

• Encourage the NIH Prevention Consortium to 

assess research portfolios on women’s health;

• Document and enhance all research on women’s

health across all agencies (NIH, CDC, HRSA, 

the Indian Health Service, the Agency for Health

Care Policy Research, and the Social and Mental

Health Services Administration);

• Use technology to share strategies (i.e.,Websites);

• Utilize practice-based community research, 

physicians’ networks (combined AHCPR/HRSA 

initiative) to test preventive intervention;

• Promote federal/state coordination; public-private

partnerships in implementing effective preventing

interventions;

• HRSA National Clinical Network — state and

regional levels; and

• Collect data on the physical and mental health

needs and health status of homeless, migrant, 

and seasonal women farm workers.

References

1 Mrazek, P.J., and R.J. Haggerty, eds. 1994. Reducing risks

for mental disorders: Frontiers for preventive intervention

research. Washington, D.C.: National Academy Press.

2 Gilligan, C. 1982. In a different voice. Cambridge, MA:

Harvard University Press.

3 Moen, P., J. Robison, and V. Fields. 1994. Women’s work

and caregiving roles: A life course approach. J Gerontol:

Soc Sci 49:S176–86.

4 Markus, H. and D. Oyserman. 1989. Gender and

thought: The role of the self-concept. In Gender and

thought, eds. M. Crawford and M. Hamilton. New York:

Springer-Verlag, pp. 100–127.

5 U.S. Department of Health and Human Services. 1991.

Healthy people 2000: National health promotion and disease

prevention objectives. DHHS pub. no. (PHS) 91–50212.

Washington, D.C.: U.S. Government Printing Office.

6 Mrazek and Haggerty. Reducing risks for mental disorders.

7 Field, T.M., et al. 1980. Teenage, lower-class, black 

mothers and their preterm infants: An intervention 

and developmental follow-up. Child Dev 51:426–36.

8 Berruta-Clement, J.R., et al. 1984. Changed lives: The

effects of the Perry Preschool Program on youths through 

age 19, High/Scope Educational Research Foundation.

Monograph 8. Ypsilanti, MI: High/Scope Press.

9 Kellam, S.G. and G.W. Rebok. 1992. Building developmental and etiological theory through epidemiologically

based preventive intervention trials. In Preventing antisocial

behavior: Interventions from birth through adolescence, eds.

J. McCord and R.E. Trembly. New York: Guilford Press.

10 Sandler, I.N., et al. 1992. Linking empirically based 

theory and evaluation: The Family Bereavement 

Program. Am J Comm Psychol 20(4):491–523.

11 Caplan, M., et al. 1992. Social competence promotions

with inner-city and suburban young adolescents: Effects 

on social adjustment and alcohol use. J Consult Clin 

Psychol 60:56–63.

12 Renick, M.J., S.L Blumberg, and H.J. Markman. 1992.

The prevention and relationship enhancement program

(PREP): An empirically based preventive intervention

program for couples. Fam Relat 41:141–47.

13 Olds, D.L., et al. 1988. Improving the life-course development of socially disadvantaged mothers: A randomized

trial of nurse home visitation. Am J Public Health

78(11):1436–44.
115

VOLUME 4

14 Price, R.H., M. van Ryn, and A. Vinokur. 1992. Impact 

of a preventive job search intervention on the likelihood 

of depression of the employed. J Health Soc Behav

33:158–67.

15 Mittleman, M.S., et al. 1995. A comprehensive support

program: Effect on depression in spouse-caregivers of 

AD patients. The Gerontologist 35:792–802.

16 Silverman, P.R. 1988. Widow-to-widow: A mutual 

help program for the widowed. In Fourteen ounces of 

prevention: A casebook for practitioners, eds. R. Price, 

et al. Washington, D.C.: American Psychological 

Association, pp. 175–86.

17 Mrazek and Haggerty. Reducing risks for mental disorders.

18 Beardslee, W.R., et al. 1992. Initial findings on preventive

intervention for families with parental affective disorders.

Am J Psychiatry 149:1335–40. 

19 Department of Health and Human Services Advisory 

Panel on Alzheimer’s Disease. 1992. Third report of 

the advisory panel on Alzheimer’s disease, 1991. DHHS 

pub. no. (ADM)92–1917. Washington, D.C.: U.S. 

Government Printing Office. 

20 Lichtenberg, P.A. and J.T. Barth. 1990. Depression 

in elderly caregivers. Med Psychother 3:147–56.

21 Kavanaugh, K.H. and P.H. Kennedy. 1992. Promoting 

cultural diversity: Strategies for health care professionals.

Newbury Park, CA: Sage Publications.

22 Locke, D.C. 1992. Increasing multicultural understanding: A

comprehensive model. Newbury Park, CA: Sage Publications.

23 Vega, W.A. 1992. Theoretical and pragmatic implications

of cultural diversity for community research. Am J Commun Psychol 20(3):375–91.

24 Dressler, W. 1987. The stress process in a Southern Black

community: Implications for prevention research. Human

Org 46:211–20.

25 Marin, G. and B. Marin. 1991. Research with Hispanic 

populations. Beverly Hills, CA: Sage Publications.

26 Toseland, R.W. 1990. Long-term effectiveness of peer-led

and professionally led support groups for caregivers. 

Soc Serv Rev 64:308–327.

27 Cross, T.L., et al. 1989. Toward a culturally competent 

system of care, vol. I. Washington, D.C.: Georgetown 

University Child Development Center.

28 Issacs, M.R. and M.P. Benjamin. 1991. Toward a culturally competent system of care, vol. II. Washington, D.C.:

Georgetown University Child Development Center.

29 Kellam and Rebok. Building developmental and 

etiological theory.

30 Leigh, W.A. 1994. The health status of women of 

color. In The American woman, 1994–1995: Where 

we stand, women and health, eds. C. Costello and 

A.J. Stone. New York: W.W. Norton and Co.

31 Plumb, M. September 25, 1996. Untitled. Testimony 

presented at public hearing at Beyond Hunt Valley:

Research on women’s health for the 21st century. Hearing and workshop sponsored by the Office of Research 

on Women’s Health, National Institutes of Health; the 

University of Pennsylvania School of Medicine; 

Allegheny University of the Health Sciences; and 

the MCP Hahnemann School of Medicine.

32 Phinney, J.S. 1996. When we talk about American ethnic

groups, what do we mean? Am Psychol 51:918–27.

33 Walker, E.A., et al. 1995. Medical and psychiatric 

symptoms in female gastroenterology clinic patients 

with histories of sexual victimization. Gen Hosp 

Psychiatry 17:85–92.

34 Weissman, M.M. and J.K. Klerman. 1977. Sex differences and the epidemiology of depression. Arch Gen 

Psychiatry 34:98–111.

35 Katon, W. 1987. The epidemiology of depression in 

medical care. Intern J Psychiatry Med 17(1):93–112.

36 Burks, J.S. 1992. A review of the current medical aspects

of multiple sclerosis. J Neurol Rehabil 6(3):131–39. 

37 Giesser, B.S. September 25, 1996. Sexual dimorphism 

in neurologic autoimmune disease. Testimony presented

at public hearing at Beyond Hunt Valley: Research on

women’s health for the 21st century. Hearing and workshop sponsored by the Office of Research on Women’s

Health, National Institutes of Health; the University of

Pennsylvania Medical School; Allegheny University of 

the Health Sciences; and the MCP Hahnemann School 

of Medicine.

38 Manu, P., et al. 1989. Depression among patients with 

a chief complaint of chronic fatigue. J Affect Disord

17(2):165–72.

39 Krieger, N. 1990. Racial and gender discrimination: Risk

factors for high blood pressure? Soc Sci Med 30:1273–81.

40 Smith, E.M. 1993. Alcohol, drugs, and psychiatric

comorbidity among homeless women: An epidemiological study. J Clin Psychiatry 54(3):82–87.
116

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

41 Cervantes, R.C., A.M. Padilla, and N.S. de Snyder. 1991.

The Hispanic stress inventory: A culturally relevant

approach to psychosocial assessment. J Consult Clin 

Psychol 3:438–47.

42 National Advisory Council on Migrant Health. 1995. 

Losing ground: The condition of farmworkers in America.

Austin, TX: National Migrant Resource Program.

43 Blumenthal, S.J. 1994. Women and depression. 

J Women’s Health 3:467–79.

44 Spiegel, D. 1995. Psychosocial influences on cancer 

survival. In Chronic diseases: Perspectives in behavioral 

medicine, eds. M. Stein and A. Baum. Mahwah, NJ:

Lawrence Earlbaum and Associates.

45 Costa, D., I. Mogos, and T. Tuma. 1985. Efficacy and

safety of mianserin in the treatment of depression of

women with cancer. Acta Psychiatrica Scand

72(suppl.320):85–92.

46 Katz, I.R. 1993. Drug treatment of depression in the frail

elderly: Discussion of the NIH consensus development

conference on the diagnosis and treatment of depression 

in late life. Psychopharmacol Bull 29:101–108.
Women in Biomedical

Careers: Issues of

Importance to 

Young Investigators

BACKGROUND

The Office of Research on Women’s Health

(ORWH) was established in September 

1990 within the Office of the Director of 

the National Institutes of Health with three mandates,

the third of which was “to develop opportunities 

and support for recruitment, retention, re-entry, and

advancement of women in biomedical careers.” In

March 1992, ORWH sponsored a public hearing 

at which representatives of more than 70 organizations described the issues and barriers that women 

face when considering a biomedical career. A workshop that took place in Bethesda, Maryland, in June

1992, brought more than 400 women and men 

together to formulate recommendations for strategies 

to overcome these barriers. The summary report 

of that hearing and workshop, titled Women in Biomedical Careers: Dynamics of Change, Strategies for 

the 21st Century, provided a starting point for a 

workshop on women in biomedical careers, which 

convened on September 27, 1996, in Philadelphia.

That report presented nine areas of concern: 

1. recruiting women for biomedical careers;

2. visibility: role models and mentors;

3. career paths and rewards;

4. re-entry into a biomedical career;

5. family responsibilities;

6. sex discrimination and sexual harassment;

7. research initiatives on women’s health;

8. gender sensitivity; and

9. minority women in science.

Although women are entering medicine and 

biomedical research in increasing numbers, they are

still not represented in the upper ranks in numbers

comparable to their male counterparts. Figures nationwide attest to this trend. According to a report by the

Association of American Medical Colleges, 41 percent

of medical students are women, 32 percent of assistant

professors in medical schools are women, 20 percent 

of associate professors are women, and 10 percent of

full professors are women. The percentage of women 

at the highest professorial rank at Allegheny University of the Health Sciences, which boasts a higher than

national average, is only 17 percent. Clearly, women 

in biomedical fields face unique challenges at all stages

of a career, which is why the cochairs of this working

group suggested eliminating the word “young” from 

the original working group title and focusing on 

issues for women investigators in general.

PROGRESS SINCE 

ESTABLISHMENT 

OF ORWH

The working group participants described new

programs at their institutions designed to help women in

biomedical careers. Among those programs discussed

were educational efforts aimed at middle school girls,

fellowships designed to buy protected time for junior

Cochairs

Eleanor Shore, M.D., M.P.H

Harvard Medical School

Anne Sassaman, Ph.D.

National Institute of Environmental Health Sciences

National Institutes of Health

Rapporteur: Rosanne Singer

117

VOLUME 4
118

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

faculty, and re-entry programs for biomedical

researchers. Those programs are organized in 

this section under the following headings:

• Promoting career growth (buying protected time);

• Re-entry;

• Precollege programs;

• Sexual harassment and discrimination;

• Leadership development;

• NIH intramural initiatives; and

• Minority women efforts.

Promoting Career Growth (Buying Protected Time)

Dr. Eleanor Shore talked about Harvard Medical

School’s 50th Anniversary Program for Scholars in

Medicine, created in 1995 to provide ten fellowships a

year for junior faculty. The program is one of Harvard

Medical School’s efforts to increase representation of

women in the higher faculty ranks. The women or men

granted these fellowships must not only demonstrate

academic promise but also be experiencing increased

family or personal responsibilities that might be alleviated by a grant of $25,000. While not intended to 

provide total support, one of these fellowships might

allow a physician to take time off from some clinical

responsibilities in order to protect time to write a grant

application, prepare a manuscript, complete a research

project, or develop new curriculum. A scientist might

use the fellowship support to pay for additional laboratory assistance at a time when there is not yet independent funding. The Office of Faculty Affairs at 

Harvard intends to continue these fellowships, with 

a new competition each year, for at least 5 years. 

The first year’s fellowships were granted to nine 

women and one man out of 210 applicants.

Re-entry

Dr. Anne Sassaman talked about the ORWH 

Re-entry Program, which was developed in 1992 

as a pilot program but is now a trans-NIH program

supported by 17 institutes and centers. The program

has helped women and men who have been out of the

biomedical research arena because of family responsibilities but who have strong potential to resume active

research careers. By providing administrative supplements of up to 3 years to existing NIH research grants,

the Re-entry Program supports full- or part-time

research by these individuals in a program designed 

to update their existing research skills and knowledge.

At the completion of the supplement, most re-entry 

scientists are in a position to apply for the next step of

funding — a career development award or a research

award. An assessment of the program done in the fall 

of 1995 found the research supplements useful in 

re-establishing careers and that most of the initial 

26 recipients were gainfully employed in research 

after 2 years. Most participants also felt that the 

mentoring component of the program was vital. The

program is currently underutilized, and NIH wants 

to get the word out to more potential applicants.

Precollege Programs

Data have clearly established that most kids leave

the fifth grade thinking that science is neat and is

something they might want to do; however, these same

students at the high school level, especially the girls,

think that science is not something they would consider

as a career. The focus of the NIH Office of Education

(OE) is students — kindergarten age and up. Dr. Bruce

Fuchs, acting director of that office, talked about efforts

to reach girls and underserved populations in the precollege years. With funding from the ORWH, OE is

working on a series of posters aimed at middle school

girls that depict women in medical research. OE has

also created a World Wide Web site aimed at middle

and high school students. Some of the components 

of the site are “Research in the News,” which talks

about news and breakthroughs in science; “Cool

Links,” which points users to other science education

resources; and “People Doing Science,” which profiles a

variety of NIH employees, for example, a genetic counselor, a speech pathologist, and a medical librarian. 
119

VOLUME 4

Dr. Margaret Kemeny, Chief, Division of Surgical

Oncology, Department of Surgery at North Shore 

University Hospital in Manhasset, New York, said 

that her department has also focused on encouraging

girls in middle school to pursue biomedical careers.

The department is developing a slide show for middle

school students showing women of various ethnic 

origins performing a variety of jobs in surgery. When

completed, this show will be presented to students 

by a woman surgeon.

Sexual Harassment and Discrimination

For information about the sensitive issues of 

sexual harassment and discrimination, the working

group participants recommended several publications.

The Council of Graduate Medical Education’s Fifth

Report: Women and Medicine found that the greatest

obstacle for women in medicine is sexism. Men’s sensitivity to women’s issues in biomedical careers could

be appreciably enhanced if they were to read this report.

The Association of American Medical Colleges offers 

a variety of materials on the status of women in medicine — from statistics on women at all levels to a 

compendium entitled Building a Stronger Women’s Program. Janet Bickel’s book Enhancing the Environment for

Women in Academic Medicine (1996) includes chapters 

on sexism in medicine and on salary-equity programs.

The Department of Surgery at North Shore University Hospital in Manhasset sends The Pocket Mentor

to all new interns but particularly targets the women

interns. A good resource for all institutions looking 

for women candidates is the reference manual that 

lists women with their subspecialty of medicine. The

book by Harvard’s Dr. Constance Buchanan, Choosing

To Lead, addresses “Mommy-track” issues and suggests

that if women are to take their rightful place in helping to lead the planet, they cannot assume the primary

role in raising children; nurturing must be shared

equally by women and men.

Leadership Development

Dr. Donna Murasko, Professor and Acting Chair 

of the Department of Microbiology and Immunology 

at Allegheny University of the Health Sciences, talked

about the institution’s program, Emerging Leaders in

Academic Medicine, which was developed through the

Office of Faculty Affairs. This program, open to many

institutions, is designed for women at the associate

professor level who want to progress to administrative

levels, such as department chair. They must be referred

by their deans to attend three groups of meetings. At

these meetings they attend workshops on leadership

skills, e-mail and the Internet, and mentoring. The

Emerging Leaders program requires the active participation of the deans, who must attend at least 1 day 

to work on ongoing problems at their institutions.

NIH Intramural Initiatives

Catherine Didion, Executive Director of the 

Association for Women in Science, distributed materials about her organization’s programs, including a 

leadership conference for midcareer women in science.

Each participant must be sponsored by her institution,

and she must attend workshops on how to negotiate,

communicate, and so forth.

James Alexander of the NIH Office of Education

described the Postdoctoral Fellows Committee, an

intramural career development program. Although 

not gender-specific, women have been active in the

program. In a series of workshops titled “Survival

Skills,” attendees learned about negotiating job offers,

life as a professional, and making oral presentations.

Job fairs, a Web site, and alternative career workshops

also assist postdoctoral fellows. Another OE program

that should help young women pursuing careers in 

science is the Predoctoral Internship Award for recent

college graduates to spend a year in a laboratory while

applying to graduate school. This program should have

an advantage over some of NIH’s summer internships

because of the length of time. 

Dr. Barbara Karp, Associate Clinical Director,

National Institute of Neurological Disorders and Stroke

(NINDS), discussed the purpose of the Women Scientist Advisory Committees, started 5 or 6 years ago at

NIH. These committees have successfully helped
120

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

women throughout NIH institutes on issues such as

pay, promotion, and tenure equity. The discrepancy between women’s and men’s salaries seems to have arisen,

in part, because women do not ask for pay raises at 

the same rate men do. NINDS has been using federal

authority to grant single-time pay raises to women.

Minority Women Efforts

Dr. Bruce Fuchs talked about NIH plans to offer 

15 to 20 annual undergraduate scholarships to students interested in science who are disadvantaged 

culturally, racially, financially, or even personally. The

program would offer a stipend for the student to live 

at NIH every summer and do research, with a guaranteed position at the participating institute after 

completion of graduate or medical school.

Dr. Carol Brown of the Department of Surgery at

Memorial Sloan-Kettering Cancer Center in New York

City described a program that her department jointly

sponsors with the Association of American Medical

Colleges. The program offers a minority faculty development seminar each fall, at which minority women

vastly outnumber minority men. She also described 

a program sponsored by the American Association 

of Cancer Researchers that sets up mentorships and

offers funding for minorities to attend meetings.

Although the program is not specifically for 

women, many participants are minority women.

GAPS IN ADVANCEMENT

The second part of the work session began with 

a discussion of the gaps and barriers that still hinder

women in biomedical careers. The many points discussed can be summarized in four basic statements:

1. Mentoring, as it exists, is often inadequate 

for the needs of women and minorities.

2. The balancing of career and domestic roles 

lags behind in the biomedical arena.

3. The lack of institutional support for career 

development hinders women from advancing

through the ranks.

4. Minority women are still not visible enough 

in biomedical careers.

Mentoring

Mentoring is a complicated issue, raising questions

about how many mentors a woman should have to

how a man effectively mentors a woman in an era of

concerns about sexual harassment and sexual harassment charges. The complexity of the issue probably

explains in part why there are still so many gaps and

questions on the subject. 

During the discussion, Dr. George Bryan suggested sexual harassment should not be a concern 

if one separates the personal from the business by

keeping mentoring sessions in the office during business hours. The business of mentoring, he said, is 

listening carefully and offering suggestions. 

Dr. Roxanne Rodney of Columbia University’s 

Division of Cardiology suggested that because women

do not have access to informal mentoring networks,

they require a formal mentoring program. Dr. Shore

said that it is important for a woman to establish herself

as an independent academic, getting what she needs

from a variety of mentors. Dependence on a single

mentor may be hazardous because that mentor may

leave, may become a competitor, or may have expertise

in only one of several areas a woman needs. Dr. Leah

Dickstein from the Department of Psychiatry and

Behavioral Sciences in the School of Medicine at the

University of Louisville expressed a similar view and

said that a woman’s number one advisor is herself, 

and that she needs an array of assistant advisors so 

that she will not be left helpless if her central mentor

does not help her. Dr. Kemeny stated that in many 

disciplines mentors do not even exist and that in

surgery, specifically, few people are interested in 

furthering a person’s career.

Stephanie Bird of the Massachusetts Institute of

Technology, a member and past president of the Association for Women in Science, suggested that, although

mentoring is important for everyone, it may be especially vital for underrepresented groups. She specified
121

VOLUME 4

areas of basic science and research in which many

trainees are foreign born and need help in the basics 

of understanding how the system works, as well as in

learning how to advance through the ranks. Sharon

Jackson, a clinical researcher with the NIH’s National

Institute of Allergy and Infectious Diseases, said that

there is a gap in the definition of mentoring that does

not take into account someone like herself who may

have a variety of mentoring requirements not only as 

a woman but also as a woman of African-American 

and Caribbean descent.

A Biomedical Career in Today’s World

The roles and boundaries of modern women and

men in their careers and domestic lives are no longer

distinct by gender. There is no longer a clear divide

between men as breadwinners, able to spend unlimited

hours in their career roles, and women as housewives

who raise the children. Therefore, an updated concept

is needed of how to balance a biomedical career with

home life and other responsibilities.

Dr. Brown said that only one way is still considered the way to succeed in a biomedical career and that

involves giving up any outside life and family. That

perception needs to change, and groups such as this

working group should make recommendations and 

ask questions such as “Why not work on changing

institutional perceptions?,” “Why not day care centers at institutions?,” and “Why are there meetings at

7:00 a.m.?” Dr. Shore mentioned that after 100 years,

Johns Hopkins moved its medicine grand rounds from

Saturday mornings to Friday mornings in order to be

more accessible to women with young children. Nancy

Teed, project manager and senior analyst at Houston

Associates, Inc., mentioned that although women reentering a field may have gained many skills outside

that field, their newfound skills are not accepted in 

the workplace, and their reputations are tainted by

judgments like “They don’t care enough” or “They’re 

not good enough.”

Institutional Responsibility and Career Development

The working group expressed concern about the

serious gap in institutional programs and support for

women in career development. Each major institution

should have programs to help its faculty members

progress through the ranks, but they should also offer

programs for professional development tailored to

women’s needs. Institutions lack a structure of rewards

for women and fail to recognize that this support is 

in their own best interest.

Minority Women in Biomedical Careers

For women and men, minorities are underrepresented in biomedical careers. Too few minority women

pursue scientific and biomedical careers, including

African-American and Asian-American women, and 

too few African-American men are in scientific and 

biomedical careers.

RESEARCH 

RECOMMENDATIONS 

Acknowledging that changing institutional attitudes and behavior is slow work, the working group

presented seven recommendations for fostering the

growth of women in biomedical careers. The group 

recognized that only a few women can be helped 

by any given program or fellowship, but it perceived 

these programs and women as models for ongoing

change around the country.

Define, Facilitate, and Reward Mentoring

Progress can be made in helping women advance 

in their biomedical careers if they have the proper

mentoring. To facilitate the mentoring process, the 

following steps should be taken:

• Define mentoring as it applies to women and minorities. Mentoring is not just one kind of activity 

or service; the concept should be made relevant 

to women in biomedical careers.

• Train individuals to be mentors. While some people

may be natural mentors, others would be good

mentors if provided effective training.

• Reward mentoring institutionally. For example, one 

of the ten Harvard fellowships awarded $5,000 
122

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

to the mentor selected by the fellowship recipient

as a person who had stepped forward to assist 

a more junior colleague.

• Counteract institutional attitudes that penalize mentors

for their efforts. In academia and industry, individuals in the highest leadership roles should assume

the responsibility of counteracting the negative

influences on mentors.

Define What Work Is; Study the Different 

Ways Men and Women Spend Their Days

A new paradigm is needed for what a career path is.

Instead of talking exclusively about “women’s issues,”

we should also talk about generational issues. Balancing

work and family is not just a woman’s problem; today,

women and men care about flex time, dual careers, 

and making institutions more responsive to all.

Participants recommended that institutions recognize the legitimacy of different work styles. A perception persists that women in biomedical fields work

part-time or are not fully committed to their fields. For

example, studies show that men physicians on average

put in 57-hour workweeks, while women physicians

average 55 hours per week. Men take time to go out 

to lunch and to exercise, and they consider those activities to be part of their workday. Women, on the other

hand, want to get the job done and get home to children or families. Both may work the same number 

of hours, but it appears that women are not putting 

in as many hours as men.

Recruit More Women; Increase Their Visibility

Not only is it important to focus on recruiting

more women to scientific and biomedical careers, but it

is also important to increase their professional visibility

by having more women serve on editorial boards of

journals, on tenure committees, and on committees

that admit students and promote faculty.

Encourage NIH To Assume a Strong 

Leadership Role

NIH should assume a strong leadership role in

addressing the needs, issues, and barriers of women 

in biomedical careers. NIH should continue its leadership role in developing programs for teaching the

“responsible conduct of science,” and should address

such issues as gender differences, sexual discrimination, and racial discrimination in such programs. NIH

should consider sponsorship of national fellowships 

to help junior faculty buy protected time at the most

vulnerable point in their academic careers, when

expanding family responsibilities coincide with the 

need to teach, do research, compete for grants, 

publish, and practice (if a clinician).

ORWH should work with programs required of

graduate students, postdoctoral students, and all those

who do research to make sure that the issues relevant

to women’s careers are introduced. The National Institutes of Health, the National Science Foundation, and

the National Research Council are already collaborating

to develop guidelines to direct that kind of interaction.

Establish Partnerships Between Academia, 

Industry, and Professional Societies

Academia should look for ways to partner with

industrial organizations. Cross-fertilization could 

help both sectors. It is important to bear in mind 

that industrial scientists constitute the majority of 

scientists in this country. The Catalyst Foundation 

provides an example of how these partnerships 

might be approached.

Academia should also look for ways to call 

upon the strong relationship between professional 

science societies and academic institutions to help

develop programs at institutions. The impetus should

come from within the institutions, but professional

societies can serve as leverage to get institutions 

to spend their resources.
123

VOLUME 4

Encourage Each Institution To Have, as Part 

of Its Cultural Values, Assistance for Women 

and Minorities

The working group participants also recommended that each institution develop formal programs to

address inequities; the advancement of women and

minorities has to be an intramural commitment that

should be promoted through a dedicated office at each

institution. In addition, it is important to look beyond

institutional mandates and influence the level where

the real power is — with the department and division

chairs of medical institutions. These “fiefdoms” typically have no sense of responsibility toward minorities.

Financial reward to those departments that do recruit

women and minorities would go a long way. 

Gather Statistics on Gender Gap Issues Such 

as Salary, Tenure, and Percentages of Women 

at Senior Levels

Accurate, comprehensive information and statistics on women in biomedical careers should be 

collected and used as a tool. Unless actual figures 

are published, people give little credence to the

inequities that exist in salary, promotion rates, and 

so forth. However, before publishing such data, it

would be essential to seek legal consultation to ensure

that no legal liabilities are incurred. The results of 

a survey, for example, could become grist for the 

lawsuit mill. In describing how institutions set aside

money to correct inequities, the institution must 

set criteria for applicants to meet, for example, 

to encourage a department to advance women.

Public Testimony

INTRODUCTION

T O THE PUBLIC

TESTIMONY

• To direct initiatives to increase the numbers 

of women who are participants in biomedical 

research careers. 

In determining directions for these objectives, 

we look for guidance and input from the scientific 

and advocacy communities. One of the most effective

ways for us to accomplish this is through public hearings. We shall further build upon the testimony we

received through the scientific workshop.

This public hearing was convened to provide guidance and assistance to us in re-examining 

our mandates as we move toward the 21st century. 

We specifically requested participants’ perspectives

concerning continuing or emerging gaps in knowledge about women’s health and successful models 

for the recruitment, retention, re-entry, and advancement of women in biomedical careers.

Testimony was received and reviewed by our 

task force on revisiting Hunt Valley, which was the 

site of our first workshop, held in 1990, at which we

began formulating our national agenda on women’s

health research. We are fortunate to have members of

the NIH scientific community, as well as by women’s

health advocates, scientists, and health professionals

from across the country who are serving as members 

of this important Task Force.

The members of the Task Force, and all of those

who participated in our workshop, were asked to 

do the following:

• Identify scientific progress since the establishment of ORWH.

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

National Institutes of Health

127

VOLUME 4

The Office of Research on Women’s Health

(ORWH) received public testimony concerning the National Institutes of Health’s (NIH)

women’s health research agenda for the 21st century.

I am extremely pleased that so many came to

express their interest in women’s health and related

research and career issues. The giving of their time 

and energies to be with us was a sign of hope and 

support for the improvement of women’s health

through biomedical and behavioral research, and 

we were very appreciative of their efforts and 

wisdom, from which we can benefit through 

their participation and testimony.

ORWH was established within the Office 

of the Director of NIH in September 1990 and was

charged with the critical objective to give a central 

NIH focus on women’s health issues and to establish 

a science base that will permit reliable diagnoses 

and effective treatment and prevention strategies 

for women. 

The major objectives of our office are:

• To develop an integrated strategy for increased

research into diseases, disorders, and conditions

that are unique to, more prevalent among, or 

more serious in women, or for which there are 

different risk factors of interventions for women

than for men;

• To ensure that women are appropriately represented in biomedical and biobehavioral research

studies, especially clinical trials, that are supported by NIH; and
128

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

• Highlight successes in the advances of scientific

knowledge about women’s health and gender/sex

information.

• Highlight programs that have advanced women’s

health research.

• Develop strategies for identifying continuing 

or emerging gaps in knowledge and how to 

address them.

• Generate recommendations for future research 

priorities and necessary consideration of the 

biomedical/behavioral research community.

• Provide pathways for networking and collaboration among researchers.

• Consider effective implementation of research outcomes in public policy and health care of women,

with consideration of changing parameters (e.g.,

advances in biotechnology, managed care, etc.).

We appreciated hearing their recommendations

and benefiting from their expertise.

The cochairs of the Task Force, Dr. Donna Dean,

who is one of the cochairs of our NIH Ad Hoc Subcommittee on Research, and Dr. Marianne Legato, 

who is a member of our Advisory Committee on

Research on Women’s Health, presided over the 

afternoon’s proceedings.
Mary J. Berg, Pharm.D.

College of Pharmacy, University of Iowa

Mary G. Bonk, R.N.

Complications of Gynecologic Surgery (COGS)

Women’s Support Group

Mary Ann Burg, M.S.W., Ph.D.

Florida Institute for Women: The Health Gatekeepers

University of Florida

Bente E. Cooney, M.S.W.

National Osteoporosis Foundation

Michael J. Gast, M.D., Ph.D.

Wyeth-Ayerst Research

Barbara S. Giesser, M.D.

Arizona Health Science Center

Phyllis Greenberger, M.S.W.

Society for the Advancement of Women’s 

Health Research

Mary Hammond, M.D.

American Society for Reproductive Medicine

Hazel J. Harper, D.D.S., M.P.H., F.A.C.D.

National Dental Association

Laura L. Hayman, Ph.D., R.N.

American Heart Association

Penelope J. Hitchcock, D.V.M.

Sexually Transmitted Diseases Branch

National Institute of Allergy and Infectious Diseases

Lisa Kaeser, J.D.

Alan Guttmacher Institute

Virginia T. Ladd, R.T.

American Autoimmune Related Diseases 

Association, Inc.

PUBLIC TESTIMONY

P H ILADELPHIA, PENNSYLVANIA 

SEPTEMBER 25, 1996

VOLUME 4

129

Dorothy Mann

Family Planning Council

Rita M. May

Sjögren’s Syndrome Foundation, Inc.

Margaret K. McLaughlin, Ph.D.

Magee-Women’s Research Institute

Powers Peterson, M.D.

American Society of Clinical Pathologists

Marj Plumb, M.N.A.

National Center for Lesbian Rights

Linda Quander, Ph.D.

Clark Atlanta University

James M. Roberts, M.D.

Society for Gynecological Investigation

Roxanne A. Rodney, M.D.

Association of Black Cardiologists

Sheryl Burt Ruzek, Ph.D., M.P.H.

Department of Health Education, Temple University

Eleanor G. Shore, M.D., M.P.H.

Harvard Medical School

Martha Torres-Montoya, M.S.P.H.

Hispanic Women’s Health Association

Laura L. Tosi, M.D.

American Academy of Orthopaedic Surgeons

Jacqueline Lee Wolf, M.D.

Gastroenterology Women’s Coalition

Elizabeth Yoffe, M.A. 

Self
Public testimonY

130

Mary J. Berg, Pharm.D. University of Iowa

The University of Iowa is a research-based university composed of ten colleges, with a student body 

of approximately 28,000.

Dr. Berg became the first woman president of the University of Iowa in December 1995. The presence 

of a female leader in this institution, founded in 1847, gives great hope to women in academia who are 

forwarding their credentials for promotion with the expectation that fairness will prevail.

The promotion and tenure list at the University of Iowa doubled from 1995 to 1996. This remarkable 

achievement was noted at the annual ceremony of the “Celebration of Excellence and Achievement Among 

Women” in May 1996.

Mary G. Bonk, R.N. Complications of Gynecologic Surgery (COGS) Women’s Support Group

Current U.S. public health policy, statutes, and state health laws adversely affect women who have experienced complications of gynecologic surgery. Occult obstetrical injuries to the pelvic floor, and complications of

gynecologic surgery not made known to women, may lead to progressive digestive and urinary dysfunction and

disease. Diagnosis, information, and prognosis have been strictly suppressed by medical politics. Examples include

permanent ostomies surgically accomplished in the absence of fully informed consent; cancer, autoimmune diseases, and other disorders that may result from surgically implanted foreign material/devices; critical complications 

of gynecologic surgery such as post-hysterectomy pulsion enterocele and vaginal/rectal prolapse; and secret surgical

research. Patients with postoperative pain and persistent dysfunction are often relegated to psychiatry.

Information and health records of these conditions and injuries have been withheld from patients and

family/representatives under Georgia health law §31-33-2(c). Because all research in Georgia is tightly protected

from legal discovery by Georgia health laws, the family/representative is also excluded from documentive research

information. Furthermore, we believe that health care data systems, comprising patient information with diagnostic

codes, personal identifiers, and other categorical divisions, are coded with psychiatric diagnoses which blacklist

surgically injured persons and/or subjects of secret surgical research from all information and diagnostic health 

care, except in a life-threatening event. Through mental health laws, interstate compacts, and committees, there is

reinforcement beyond state boundaries by codes with personal identifiers which blacklist the patient throughout

the United States and Canada.

Investigative and documented procedures have been obtained on a patient from world experts outside of the

United States and their assessments have been sent to the patient’s established physician in Georgia. Under Georgia

health laws and regulations, this physician cannot provide the information to the patient or representative, and

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

131

third-party release of records cannot be obtained by process of Georgia law. In January 1996, a formal written 

complaint, with request for investigation of this specific case, was submitted by COGS to the Office for Civil 

Rights, HHS Region IV, in Atlanta.

COGS requests the interest of this workshop’s cochairs, leaders, and participants and asks for inquiries 

through the Freedom of Information Act to the Office for Civil Rights, HHS Region IV in Atlanta, Georgia. 

Mary Ann Burg, M.S.W., Ph.D. University of Florida

Our country needs major support to establish a National Network of Centers of Excellence in Women’s Health.

Without it, women’s health services will remain fragmented and insufficient.

Although some of the lessons from the women’s health movement of the 1970s were absorbed by mainstream

medicine, an oppressive climate still persists. Too many women have adverse experiences with the health care

industry. Too many physicians disregard their symptoms and “talk down to them.” It is clear that women’s health

care needs are different from men’s, yet they are not given the same attention and respect. This deficiency is 

reflected in morbidity and mortality statistics.

I believe that coordinating women’s health must be a top priority for those of us who provide health education, research, and services to women. A network of Centers of Excellence in Women’s Health is the most efficient

and effective remedy for today’s disjointed service delivery system.

The Florida Institute for Women: The Health Gatekeepers at the University of Florida offers a model for 

establishing a Center for Excellence in Women’s Health. We have built partnerships with other academic health

centers and women’s research institutes across the country to foster collaboration and linkage on the national 

level, which is essential to make a significant impact on women’s health. In fact, we intend to construct a firstclass National Center for Excellence in Women’s Health to foster cooperative efforts to build upon existing efforts 

to improve the sharing of data, the mentoring of researchers in women’s health, and the development of models 

for delivering women’s health services.

A long-term strategy is critical to the success of a project like a national network of Centers for Excellence. 

It will require a concerted effort from foundations, philanthropies, and other private funding groups, as well as 

volunteer organizations. It also needs formal sanction by a host academic health center in order to have the influence necessary to survive in today’s political environment. The Brain Institute of the University of Florida, which 

was founded 5 years ago by a coalition of educational and research interests, provides an exciting model for 

establishing a unique, dedicated facility.
Public testimonY

132

One of the lessons learned from the self-help movement of the 1970s — the foundation for the very notion 

that women’s health is a unique field deserving distinct services — is that in order for a cause to flourish, it must 

be firmly institutionalized. I applaud the recent RFP from the Department of Health and Human Services to 

develop a Model Center of Excellence in Women’s Health. It is an exciting start to institutionalizing women’s 

health. Now is the time to capture this strategic opportunity.

Bente E. Cooney, M.S.W. National Osteoporosis Foundation

A comprehensive national strategy to address osteoporosis, including a coordinated program of basic, clinical,

and behavioral research, is urgently needed before the baby-boom generation reaches the age of osteoporotic 

fractures. Although progress has been made during the last 5 years towards preventing, diagnosing, and treating 

this disease, there are still unanswered questions that need to be addressed.

The National Osteoporosis Foundation is the only national nonprofit organization solely devoted to reducing

the widespread incidence of osteoporosis. The major goals of our research are to uncover the molecular and cell

biology of bone and the factors that regulate bone cell activity; to identify the genetic and environmental risk factors that contribute to bone loss; and to develop methods of prevention, diagnosis, and treatment. Because women

are four times as likely to develop the disease, and based on data provided by the National Health and Nutrition

Examination Survey, NOF estimates that by the year 2000, a total of 25.5 million women either will have osteoporosis or be at risk for osteoporosis due to low bone mass. Therefore, we encourage and appreciate the continued

research efforts on osteoporosis, especially as it relates to women. It is our hope that research will address those

unanswered questions women need to learn about osteoporosis.

In basic research, questions concerning restoring and reversing skeletal functions need to be addressed. 

Moreover, investigation surrounding predetermining factors such as menopause, hereditary factors, and the 

role of genes must be explored.

Relevant to clinical research, we need to know the most efficient and cost-effective way to diagnose and treat

patients with osteoporosis. While progress has been made to isolate certain risk factors such as race, smoking,

weight, family history of fractures, and previous fractures, further research is necessary to refine and clarify risk 

factors. In addition, more clinical studies on treatment measures, including exercise, must be conducted to better

understand, prevent, diagnosis, and ultimately treat this complex disorder.

In behavior research, perhaps the most important progress we can make is in the behavior of children, 

adolescents, and young adults. We must learn to foster lifestyle behaviors that are conducive to healthy living,

thereby reducing bone loss. Adequate calcium intake, exercise, and healthy, smoke-free lifestyles must be fostered.

Also, as women approach menopause, they should discuss the potential benefits and risks of estrogen replacement

with their health care providers.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

133

The current biomedical and behavioral research for osteoporosis deserves much attention. If not provided, 

this disease will not only bankrupt our health care system, but the lives of million of women and men.

Michael J. Gast, M.D., Ph.D. Wyeth-Ayerst Research

Oral contraceptive and hormone replacement programs address a wide range of women’s health care issues.

With lower doses and changes in regimen, oral contraceptives have become safer over the years without a loss of 

efficacy. Noncontraceptive health benefits, including the prevention of sexually transmitted diseases, the lowering 

of the incidences of several of the reproductive cancers, and the prevention of a variety of medical conditions

requiring hospitalization of women have been additional benefits. Hormone replacement therapies (HRT) are 

being recognized in recent medical literature as providing superb global benefits for women’s health.

Unmet health needs of women include infertility, endometriosis, uterine fibroids, reproductive cancers, depression, and collagen vascular disease. Wyeth-Ayerst has elected to refocus it’s own women’s health care research and

development activities with a capital investment of almost $35 million and the establishment of a Women’s Health

Research Institute devoted to the medical and social issues critical to female health. The Institute is devoted to the

development of women’s health care medications. By removing the boundaries and integrating women’s health

research with the company’s other discovery efforts in areas such as heart disease, stroke, breast cancer, and Alzheimer’s disease, the company is able to leverage all of its resources to find solutions that benefit women’s health.

With a primary focus on the definition of steroids, nonsteroidal molecules, and nonhormonal targets for the

treatment and prevention of women’s health disorders, Wyeth-Ayerst also supports other biomedical and behavioral

research issues in women. Improved screening techniques, important developments in chemical synthesis and molecular biology, and genetic techniques are helping to accelerate advances. Genomic technology, in particular, holds 

the potential for uncovering the mechanisms of disease that underlie many women’s health disorders.

Wyeth-Ayerst recently funded a $16 million ancillary study to the Women’s Health Initiative (WHI) to evaluate

the role of HRT in the prevention and treatment of Alzheimer’s disease, and is also providing Premarin and Prempro

to the 6-year “WHI Memory Study,” which involves 8,000 postmenopausal women age 65 and over. Wyeth-Ayerst

is also sponsoring the Heart and Estrogen-Progestin Replacement Study, known as HERS, a 5-year, $40-million,

multicenter, placebo-controlled, double-blinded trial of the impact of HRT on approximately 2,700 postmenopausal women with heart disease.

In addition to its research program, Wyeth-Ayerst’s Women’s Health Research Institute will also disseminate

information about women’s health and support a wide variety of education programs aimed at both patients and

physicians. The benefits of HRT for protection against osteoporosis in women after menopause is one such area 

of education. 
Public testimonY

134

Barbara S. Giesser, M.D. National Multiple Sclerosis Society 

Sexual Dimorphism in Neurologic Autoimmune Disease

Sexual dimorphism in immune function is well documented. The female immune function is more vigorous

than that of men. Much of this distinction appears to be related to the most fundamental difference between the

sexes: the ability to conceive and bear children. A connection between the reproductive and immune systems has

been realized since the last century, although the complex network of interactions that are involved are only just

now beginning to be understood. Neural control is well established; however, it is becoming apparent that nervous

and immune function do not operate in an isolated fashion, but are interdependent as well.

One of the most important connections between the nervous and immune systems is via the hypothalamicpituitary-adrenal (HPA) axis. Females of several species, including humans, have more HPA responsiveness than 

do males, and have higher cortisol levels in response to stress. Even at a basic level, there appear to be differences

between the sexes. HPA axis also demonstrates communication between the neural, endocrine, and immune 

systems, for example by regulating the immune cell number, activity, and production of cytokines. Cytokines, 

in addition to their principle activities of immunoregulation, can act directly on the hypothalamus to influence

release of hormone-stimulating factors. Estrogen, progesterone, prolactin, and testosterone also have been shown 

to affect immune function. A third way in which the immune and neural systems communicate is via neurally

active substances that are produced by immune cells.

Effects of Pregnancy

Not only is immune function different in women in terms of responsiveness and activity, but there are marked

fluctuations in immune status during a woman’s lifetime. This is in marked contrast to relatively steady-state

immune function in men. The most dramatic changes in female immunity happen during pregnancy. Teleologically,

this must occur to ensure that the fetus, which is after all immunologically foreign to the mother, is not rejected.

The immunosuppression that is seen in pregnancy also leaves the mother more susceptible to infection by certain

viruses, such as rubella or herpes. There are also animal model correlates of pregnancy-associated changes in

immune function. For example, it is more difficult to induce certain autoimmune diseases in pregnant rodents,

compared to their nonpregnant controls. Two examples of this are the protective effect of pregnancy upon experimental allergic encephalomyelitis (EAE), and also experimental allergic neuritis (EAN), an animal model of 

an autoimmune peripheral nerve disease, Guillain-Barre syndrome. Additionally, skin grafts survive longer on 

pregnant than nonpregnant hosts. In humans, in vitro assays of immune cell function demonstrate decreased

response in immune cells taken from pregnant women compared to nonpregnant controls.

A number of substances are believed to be responsible for this immunosuppression, including not only sex

hormones, but several pregnancy-associated hormones and proteins, including cortisone, alpha fetoprotein, and

human chorionic gonadotropin. Pregnancy is generally associated with suppression of cell-mediated immunity, and

normal or increased activity of humoral (antibody) immune responses. It has also been demonstrated that the levels 

of cytokines that modulate the immune response are increased during pregnancy. One mechanism for mediating

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

135

this may be increasing levels of estrogen and progesterone throughout pregnancy, in addition to other immunosuppressive substances such as cortisol.

However, after delivery, the immune system rebounds back to prepregnancy levels. Clinically, these changes 

are manifest symptomatically in women with autoimmune diseases. Often there is dramatic improvement seen 

during pregnancy, with relapses occurring postpartum. These clinical changes are likely to be mediated, at least 

in part, by the different concentrations of sex hormones that are seen postpartum, in distinction to their levels 

during pregnancy.

Effects of the Menstrual Cycle

In addition to the changes that may occur in women during pregnancy, premenopausal women undergo 

cyclic metabolic and hormonal fluctuations on a monthly basis. However, in contrast to the primarily immunosuppressed state that occurs during pregnancy, immune function may be suppressed or enhanced coincident 

with different phases of the menstrual cycle. There are well-documented reports of allergic reactions, including 

anaphylaxis, occur-ring during the luteal phase of the menstrual cycle. Changes in functions of different components of the immune system have also been reported to change with different phases of the menstrual cycle. 

Lastly, many autoimmune diseases, such as lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatoid arthritis, and neurologic autoimmune and nonimmune diseases are recognized to have symptom fluctuation 

coincident with menstrual cycle phases. In addition to MS and MG, these include migraine and epilepsy.

Studies of immune function at different phases of the menstrual cycle have been somewhat contradictory. 

Some authors have reported that immune cell responsiveness is low during the midpoint of the cycle and increased

during menses, while other experiments did not support this conclusion. In another study, immune responses to

Candida, a common yeast, were shown to be reduced in women during the luteal phase. This would be consistent

with the actions of progesterone as an immunosuppressant. However, synthesis of complement was found to be

influenced by progesterone levels, and levels increased during the luteal phase of the cycle.

More recently, it was demonstrated that levels of interleukin-I are increased during the luteal phase of the

cycle. The expression of prolactin receptors on immune cells has been shown to vary at different phases of the

menstrual cycle in healthy women. It has been suggested that immune responsiveness is higher during the ovulatory phase of the cycle to ward off infection that might interfere with successful development and maturation of 

the oocyte, but that immune function is depressed following ovulation so that sperm will not be destroyed before

successful fertilization can occur. Obviously, different levels of sex hormones during different phases of the menstrual cycle can and do influence immune responses in ways that have yet to be clearly defined.

Changes in clinical status of women with autoimmune rheumatologic and endocrine diseases during menses

and pregnancy have been extensively documented. In contrast, less is known about autoimmune neurologic disease 

as a function of hormonal climate. The two most common autoimmune neurologic diseases in which there is a

clear female preponderance are myasthenia gravis and multiple sclerosis (MS).
Public testimonY

136

MS currently affects an estimated 350,000 people in this country; 73 percent of whom are women. A geographic gradient exists, with higher prevalence in temperate (as opposed to tropical) latitudes. The onset of disease 

is usually in the third or fourth decade of life. However, epidemiologic studies have shown that the risk of developing MS changes if one moves from a high-risk to a lower-risk geographic area before the age of 15. Obviously, there

are factors associated with puberty that impact on genetically susceptible individuals to manifest disease. In both

sexes, sex hormones become active at this time of life, with the female system becoming more “turned on,” and

testosterone exerting a more constant immunosuppressive effect. It is tempting to speculate that pubertal hormonal

changes are, at least in part, responsible for the female predilection to MS, but this remains to be proven.

The pathophysiology of MS has been demonstrated to be autoimmune in nature, and primarily involves 

T-cell-mediated immunity, although abnormalities in humoral immune function exist as well. CNS myelin autoreactive T-cell clones are recruited into the brain and spinal cord to attack myelin and oligodendrocytes. Several

cytokines have been identified as being key to this cascade of immune events that result in demyelination.

Cytokine Involvement in MS

IL-1. Monocytes from patients with MS have been shown to produce more IL-I than cells from healthy 

controls. IL-1-positive cells have been identified on chronic active plaques in the brains of MS patients.

IL-2. IL-2-positive cells have been demonstrated in chronic active plaques in the brains of patients with MS.

Some authors have reported increased levels of IL-2 and sIL-2R (the soluble IL-2 receptor, a marker of immune

activation) in MS patients compared to controls, although there was no correlation with clinical status. A study 

of patients with RA reported that levels of sIL-2R decreased in response to increased stress.

TNF alpha. TNF alpha has been demonstrated to mediate myelin damage and is cytotoxic to oligodenrocytes 

in vitro. Levels of TNF alpha are higher in MS patients than healthy controls, and they have been shown to 

increase just prior to exacerbations. 

IL-6. One study has demonstrated increased levels of IL-6 in MS patients compared to healthy controls. 

To date, it has not been definitively demonstrated that MS has an affect on normal hormonal flux, fertility, or 

pregnancy outcome. There is one report of lower testosterone levels in 20 percent of a small sample of men 

with MS. There have been a few studies which have reported slightly different hormone levels in MS patients 

compared to non-affected controls, i.e., higher prolactin levels, and one report demonstrated an increased 

prolactin level in women with relapsing remitting MS just prior to exacerbation, with a drop in levels during 

clinical remission. These data need to be interpreted cautiously, as factors such as stress may be involved with 

these apparent hormonal changes. At least two studies in the animal model of MS, EAE have reported that the 

induction and severity of disease can be blocked by bromocriptine, a compound which inhibits secretion of 

prolactin at the neural level. Other observations in EAE have noted that administration of exogenous estrogen 

can suppress the disease in susceptible rodents. To date, there have been no systematic investigations of the 

use of hormone replacement or supplementation therapy as a treatment for MS.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

137

There have been few studies on the effects of the menstrual cycle on MS. One anecdotal report in the 1950s

commented upon a patient who had regular exacerbations, at the time of menses, which were controlled by the

administration of oral contraceptives. More recent studies have investigated the effects of the menstrual cycle by

means of self-report questionnaire. In our series of 150 premenopausal women who responded to a self-report

symptom checklist, 70 percent reported that their symptoms changed at a consistent time during the month; 

60 percent reporting worsening of neurologic symptoms within 1 week of onset of menses. A much smaller 

sample in Great Britain, which polled 11 premenopausal women, reported premenstrual worsening of neurologic

symptoms in 82 percent of the respondents. These are very preliminary data, and more work needs to be done 

in this area to confirm and expand these results.

As stated, MS does not affect fertility, pregnancy outcome, or lead to an increased number of congenital defects.

However, the effects of pregnancy on MS have been the subject of multiple studies. The data indicate that clinical

exacerbations actually are decreased during the 9 months of pregnancy. Most patients do quite well during pregnancy although symptoms of MS, which are normally present in the nonpregnant state, such as fatigue, urinary

symptoms, and difficulty in ambulating, can be made worse by the physiologic changes which accompany pregnancy.

The decrease in number of relapses during the pregnant period would seem to be congruent with the overall

immunosuppression at this time, and therefore it is not surprising that there is an increase in the number of relapses

seen in the several months immediately following delivery. Of interest is the fact that women who breast feed (and

therefore have higher prolactin levels) do not have more relapses than women who bottle feed. It is important to

note that, although the number of relapses are increased in women with MS who become pregnant compared to

nonpregnant patients, the long-term disability in both groups is not significantly different.

Myasthenia gravis (MG) is another neurologic autoimmune disease, which currently affects an estimated

40,000 Americans. The autoimmunologic abnormality in MG is the presence of anti-acetylcholine receptor antibody. This interferes with neuromuscular transmission and causes weakness. Interestingly, in patients under age 50,

the female to male ratio is approximately two to one, and the peak onset of symptoms occurs between age 20 to

30. After age 50, the sex ratios become more equal.

Reports of effects of the menstrual cycle on MG vary. Some authors state that up to 40 percent of women with

myasthenia show worsening of symptoms just prior to menses, which do not respond to treatment with estrogen or

oral contraceptives. There is at least one report of cyclic variation in the levels of acetylcholinesterase with patients

showing worsening of symptoms perimenstrually, when the enzyme activity was high, and clinical improvement

when enzyme levels were lower at different times in the cycle. It would be of interest to track levels of antibodies 

in women with MG at different times of the menstrual cycle and see if there are clinical correlations.

Estimates are that of those women with MG who do become pregnant, approximately two-thirds will stay 

the same or improve, with exacerbations being more likely during the first trimester. In a fashion similar to MS, 

the postpartum period seems to predispose to exacerbations, and it is thought that this may be due to the loss of

some of the immunosuppressive factors that are produced during pregnancy. Approximately 10 to 20 percent 
Public testimonY

138

of myasthenic mothers will transfer antibodies to their offspring and produce the syndrome of neonatal myasthenia,

but otherwise, MG does not appear to affect fertility or other pregnancy outcomes.

Future Research Directions

While it is clear that autoimmune disease predominates in women as a result of a series of intricate interactions

between the neural, endocrine, and immune systems, the precise mechanisms by which this happens remain to be

elucidated. It is well known that autoimmunity to self components exists in all healthy persons, but it is not understood why in some individuals, this escalates into the manifestations of an autoimmune disease. There are large

gaps in our understanding of autoimmunity not only at a cellular and molecular level, but also as related to clinical

phenomena, both in healthy people as well as in patients with autoimmune disease. Several lines of investigation

are immediately suggested by the information that is already known. For example, are levels of sex hormones in

men and women with neurologic autoimmune disease different than healthy age-matched controls? Are there differences in levels of immunologically active substances such as cytokines during different phases of the menstrual

cycle in healthy persons, and do cytokine levels correlate with hormone levels? Is there dysregulation of normal

cytokine/hormonal relationships in patients with autoimmune disease? What other hormone receptors exist on

immune cells in addition to the ones already described? At what other sites in the brain can substances such as

cytokines affect function?

What is the natural history of autoimmune neurologic disease such as MS in women as a function of hormonal

milieu? Do differences in neurologic status and clinical course exist between premenopausal and postmenopausal

patients? What percentage of premenopausal women with MS in a large population-based sample have quantifiable

changes in neurologic symptoms and function at a predictable time during the menstrual cycle? Do the abnormalities of the immune response that have been demonstrated in MS patients impact upon hormonal function? What

part do lesions at a neural level play in dysregulation of normal endocrine/immune interactions? Finally, can 

manipulation of sex steroids be useful as therapeutic modalities for neurologic autoimmune disease? These 

and other questions provide fertile ground for future research endeavors.

Phyllis Greenberger, M.S.W. Society for the Advancement of Women’s Health Research

Gender-based biology — the examination of basic biological and physiological differences between men and

women — is the next frontier for women’s health research. This protocol has implications for disease research, 

clinical practice, disease prevention, medical education, and public health policy.

It is a testament to those of us here that there is recognition of gender differences in disease manifestation. 

While we may continue to encounter skepticism on this, none of us doubt the reality and importance of 

gender differences.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

139

There is increasing evidence to support the study of gender-based biology. Scientists have observed basic 

biological differences between the genders in areas of research as diverse as genetics, endocrinology and metabolism, cancer, and pharmacokinetics. These differences can significantly impact disease development and 

treatment. An organized and methodological approach to gender-based biology could promote better understanding of why gender differences exist and their implications.

Until recently, these discoveries were a by-product of other research. We need to create a system where such

observations are recorded and disseminated along with findings from more specific gender-based research studies.

We believe that the potential implications of gender-based biology are dramatic — for research, clinical practice, disease prevention and manifestation, medical education, and public health policy. Issues associated with

women’s health represent the cutting edge of today’s knowledge and have the potential to dramatically change 

the way clinical medicine is conducted.

Hazel J. Harper, D.D.S., M.P.H., F.A.C.D. National Dental Association

Testimony prepared by Georgetta Manning-Cox, D.D.S., M.P.H., F.A.C.D., Howard University College of Dentistry;

Hazel P. Haynes, D.M.D., M.P.H., University of Texas Health Sciences Center at San Antonio; Hazel J. Harper, D.D.S.,

M.P.H., F.A.C.D., National Dental Association; Shelia S. Price, D.D.S., Ed.D., West Virginia University School of Dentistry; 

and Marilyn Woolfolk, D.D.S., M.P.H., University of Michigan School of Dentistry.

Issues in Women’s Oral Health: The Quest for Answers Continues

Dr. Pinn, and distinguished panelists, thank you for providing the National Dental Association with this 

opportunity to present testimony during this important hearing. We would first like to acknowledge and thank 

you for your tireless commitment to women’s health. We extend our highest commendation to the NIH Office 

of Research on Women’s Health for their steadfast pursuit of a research agenda that will provide answers to some 

of our most complex and compelling questions. The quest for answers continues.

From our perspective, there are many factors that affect a woman’s oral health status. The special oral health

needs of women, that set them apart from men, are greatly influenced by hormonal fluctuations, age, and stress.

Socioeconomic status and its relationship to health status and access to care is also a very relevant issue. Since

minority women are disproportionately represented in the low socioeconomic status, differential access has been 

a contributing factor to poor health among African Americans and other minority groups.

For the purpose of this presentation, however, we would like to focus on some factors that are age-related,

gender linked, or specifically problematic for minority women: namely, menopause, osteoporosis, diabetes, and

stress. A brief description of these conditions captures only a few of the common dilemmas. The role of vitamins,
Public testimonY

140

the benefit of hormone replacement therapy, and the effects of stress are questions that shout resoundingly for 

more research. In addition, because of their relevance to prevention as well as health outcome, issues related 

to “access to health care” should be included in any meaningful women’s health research agenda.

Menopause

Throughout a female’s lifetime, hormones and their “abundance of” or “lack of” greatly influence the physical

and psychological health of women. In research conducted over the last four decades, we have learned much about

the oral cavity’s response to phasic hormonal fluctuations including: puberty, pregnancy, menses, menopause, and

postmenopause.1–5 However, as millions of baby boomers stand at the threshold of menopause, we realize that

there are still too many unanswered questions, too many problems, and not enough solutions.

Oral manifestations during menopause are profoundly different from those during other phases of a woman’s

life. For example, studies have revealed that increased sex hormone levels (estrogen and progesterone) correlate

with increased gingivitis, due to changes in the subgingival microflora,2 and the synthesis of prostaglandin is a 

key to altered gingival inflammatory response.6 On the other hand, however, with the cessation of menses and 

hormonal deprivation, although there are some associated changes in the gingiva, including gingival atrophy and

menopausal gingivostomatitis,7 there are more problems in other areas of the oral cavity. The most common complaints are pain, burning, and altered taste sensations. In some women, salivary gland changes cause a reduction 

of the salivary flow which results in xerostomia or dry mouth. One or more of these complaints have been reported 

in 20 to 90 percent of menopausal and postmenopausal women.7–10 Another study revealed the vast majority 

of women (80 percent) with burning mouth syndrome experienced pain from 3 years prior to 12 years after 

the onset of menopause.11

The cytological composition of the oral mucosa is strikingly similar to that of the vaginal mucosa. However,

what is still unclear is whether the oral epithelium is as good an indicator of hormone levels as the vaginal epithelium and whether oral epithelium exhibits the same characteristic changes.7 Additional research in this area

would be very beneficial.

Regarding decreased salivary flow as a consequence of age, it is now generally accepted that in an otherwise

healthy individual salivary gland output does not diminish with age.7 The findings of many studies investigating

salivary functions and complaints of burning and/or dry mouth have, however, yielded conflicting results. It was

reported as early as 1951,8 that the symptoms of oral pain and discomfort were relieved by the administration of

estrogen, either systemically or topically.7 However, in some studies the administration of estrogen, either topically 

or as systemic supplementation, revealed no significant change in salivary flow.7

Since women comprise 60 percent of the population age 65 and older and 72 percent of the population age 

85 and older, older adults are at risk for chronic dental conditions.12 The special needs of the geriatric patient will

most frequently be the needs of women;12 with women of low socioeconomic status and/or African American and

other minorities heading the list of high-risk patients. Continuing research on the appropriateness and effectiveness

of estrogen in hormone replacement therapy will be extremely valuable in determining its role in the oral health 

of menopausal and perimenopausal women.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

141

Osteoporosis

Changes that occur in the alveolar bone of the jaw, as a result of the aging process, are similar to those occurring in the remainder of the skeletal system. These include osteoporosis, decreased vascularity, reduced metabolic 

rate, and reduced healing capacity. There currently exists a very subtle distinction between oral bone loss and

osteoporosis on one hand, and definite linkages, although still unclear, between the two, on the other hand.

Osteoporosis is characterized by low bone mass and microarchitectural deterioration of the bone, which leads 

to increased bone fragility and risk of fracture.13 Oral bone loss can result from several systemic diseases and has

been linked mainly with periodontitis or residual ridge resorption.13 A growing body of data suggests, however,

that older women are at risk for both osteoporosis and oral bone loss;13 and that generalized bone loss from systemic osteoporosis may render the jaws susceptible to accelerated alveolar bone resorption and subsequent tooth

loss. Estrogen deprivation is an initiating factor for osteoporosis. By contrast, periodontitis is initiated by a bacterial infection, and alveolar ridge resorption is a consequence of tooth loss.

In edentulous women, the inevitability of age-advancing ridge resorption, coupled with the consequences 

of osteoporosis, is particularly troubling. It has been reported that the height of the alveolar ridge in edentulous

women correlated with total body calcium, which may indicate that women with severe postmenopausal osteoporosis, retain less bone following tooth loss.14 Rapid and continuing mandibular bone resorption contributes 

to ill-fitting dentures that require frequent replacement. In addition, in extreme cases, it becomes virtually impossible to fabricate a functional mandibular denture that has any retention or stability, because of loss of bone 

height. Decrease of mandibular bone mass has been positively correlated with tooth loss in female subjects.15

In many cases, deterioration of the bone mass also causes the mandibular nerve to be located in a position more juxtaposed to the surface of the gingiva. This position creates a condition where the proximity of 

the nerve to the denture’s undersurface makes this interface extremely painful. The patient is unable to wear 

the denture, because any pressure contact at the denture/nerve interface is intolerable. This can give rise to 

serious nutritional deficiencies.

As a rehabilitative measure, osseointegrated dental implants, strategically placed in areas with adequate 

bone height, are proving to be very advantageous. The role of osseointegrated implants retarding further bone 

loss in osteoporotic patients is an area that warrants further study.

Preventive measures for osteoporosis include early identification of the risk factors, estrogen replacement 

therapy (ERT), calcium supplementation, and vitamin D.16 In one longitudinal study which began in the late

1970s, researchers have evaluated the risks and benefits of ERT in one population of older women in the California retirement community of Leisure World. The ongoing results of this study indicate that ERT is the most

effective method for preventing osteoporotic bone loss and fractures in postmenopausal women. In this population, ERT reduced the risk of hip fractures by 50 percent. In addition, estrogen users have retained more 

natural teeth than nonusers.17
Public testimonY

142

Early detection of osteoporosis can be accomplished by new and improved diagnostic tests. The current

method of diagnosing osteoporosis is the bone mineral density test (BMD test). The most commonly used BMD 

test is DXA dual-energy x-ray absorptiometry. There is evidence to suggest that DXA measurements at the time 

of menopause many accurately predict future fracture risk.7 It is hoped that in the near future, serum and urine

tests that assess biochemical markers will be available to determine resorption and bone formation, as well as 

identify possible causes of bone loss.7

Current FDA-approved therapeutic options for the treatment of osteoporosis include: ERT, calcitonin,18 and

alendronate.7 The possible beneficial effects of fluoride on osteoporosis are also under investigation.19 Ongoing

research on the long-term effects of the therapeutic options of fluoride, and the trace elements such as zinc, 

copper, and manganese,20 will be enormously helpful for the treatment and prevention of osteoporosis.

Diabetes

Diabetes is the third-leading cause of death of among black Americans. The disease is especially common

among older black women. Over the age of 55, one out of four has diabetes.21 However, the National Center 

for Health Statistics reports that in the United States, other minorities have even higher rates of diabetes than

African Americans.21

Ten percent of the 11 million diabetics in this country have Type I Diabetes, also known as juvenile-onset 

or insulin-dependent diabetes (IDD).21 At present, there is no way to prevent Type I Diabetes, but there are 

ways to control the condition: daily insulin, a special diet, and exercise help keep the blood-glucose levels balanced. Type II Diabetes, however, accounts for more than 90 percent of all cases among blacks, mostly women. 

This condition can be controlled through diet for weight control, exercise, and possibly oral medication.21

When diabetes is out of control, oral health can be severely compromised.

Changes that can take place in the oral cavity include: cheilosis, burning sensation, decrease in salivary flow, 

and alterations in the flora of the oral cavity. The most striking changes in uncontrolled diabetes are the reduction 

in defense mechanisms and the increased susceptibility to infection leading to destructive periodontal disease.22

In addition to proper diet and exercise, stress reduction has also been found to control the disease. Stress 

can make diabetes spin wildly out of control. When this occurs, the periodontal tissues become very vulnerable to 

disease and the lowered resistance of gingival tissues gives rise to inflammation and infection. Diabetics are very

prone to disease and have impaired wound-healing capabilities. One of the early warning signs of out of control

diabetes is unmanageable periodontal disease accompanied by recurring abscesses, tooth mobility, and tooth loss.

Immaculate oral hygiene and regular visits to the dentist for removal of plaque and infection-causing bacteria

will keep periodontal disease under control. An increasing number of dentists and physicians are routinely recommending vitamin supplements for the control of periodontal disease predisposed by diabetes. Additional research

on the effects of specific combinations of vitamins, used in conjunction with pharmacotherapeutics, would enhance

the management of this disease.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

143

Stress

Tension, anxiety, worry, or fear — all are conditions of stress that can have dangerous, sometimes fatal consequences. Stress can be physical or emotional, and can also exhibit many oral manifestations. Although stress is

experienced by everyone, everyone does not respond the same way. In fact, it is not the stress itself that does the

damage, but rather the way we handle it. For far too long, the consequences of stress on women and minorities 

has been minimized or disregarded. However, current research has shed some new light on an old subject.

Although stress is an integral part of all our lives, recent research suggests that stress poses profound difficulty

for blacks and other minorities.21 The everyday struggle of dealing with prejudice and racism produces a steady

suppressed anger that many scientists believe is the reason for the explosive rate of hypertension among blacks.21

Low socioeconomic status (SES) is directly proportional to poor health status and decreased access to care. There 

is a vicious cycle of poverty and stress that compromises health status and complicates health care.

Oral manifestations of stress include a myriad of conditions: painful and recurring aphthous ulcers, gingivitis

and bleeding gums, bruxism (grinding and clenching teeth resulting in the abrasion and erosion of enamel, myofacial pain, and soreness), and temporomandibular disorders (TMD). TMDs alone, represent a cluster of related 

ailments with overlapping signs and symptoms. It is believed to be one of the most common outward manifestations of stress. However, recent research suggest that the risk factors, causative factors, and perpetuating factors, 

are multifactorial and may involve not only stress, but physical factors of dental malocclusion and the musculoskeletal relationship of jaw function to the head, neck, and face.23,26

Clinical findings in TMD include jaw aches, earaches, headaches, facial pain, muscle tenderness, joint soreness,

limited movement of the mandible, joint sounds, and even chronic pain behavior. It is estimated that while 28.96

percent of the adult population has mild or self-limiting TMD, only about 5 percent require treatment. Of those

presenting for treatment, females are estimated to outnumber males from a 9:1 to 3:1 ratio.24,25 TMDs today are

enmeshed in a raging scientific debate. Future research is needed to diagnose and classify TMDs. Unfortunately,

clinicians and researchers have reached a frustrating impasse and are unable to arrive at a consensus on the appropriate standards of clinical care for these patients. The clinical management of these patients is often very difficult

and perplexing with clinical failures estimated at 10 to 20 percent. Future research must not only bridge the 

diagnostic and treatment gaps but also focus on improving the education of the dental professional.26

Stress has been implicated in the etiology of periodontal disease, but the mechanism by which it acts as a 

pathogenic agent has not been fully delineated.27 Although much of the research conducted has focused on the

relationship between emotional stress and acute necrotizing ulcerative gingivitis (ANUG), other studies suggest 

that stress may even result in vertical and horizontal bone loss with associated pocket formation. This disease 

entity has been called “periodontal emotional stress syndrome (PESS).”28

The occurrence of ANUG, associated with negative life events and stress arising from life events and life situations, has linked psychosocial factors to this disease with abundant evidence.29 Involuntary physiologic mechanisms

that may induce stress-related periodontal disease include four major factors: impaired gingival circulation, lowered
Public testimonY

144

host resistance, decreased salivary flow, and endocrine imbalance.27 In addition to the physiologic components,

psychological distress and its relationship to myofacial face pain among women is an area currently being examined.30 The correlation of emotional stress and myofacial face pain is one that merits further investigation.

To combat stress, in addition to stress release mechanisms — like exercise — most nutritionists recommend

vitamin supplements in addition to a quality diet. Vitamin supplements are especially important for people whose

health is compromised by specific illness, stress, smoking, alcohol, or poor diet. Specific vitamins and minerals

have been found to be essential for healthy teeth and gums including: vitamin C, beta carotene (vitamin A), 

vitamin D, calcium, fluoride, magnesium, zinc, and copper.21

As far as we are concerned, health professional schools should assume more responsibility to provide adequate

training in the area of nutrition. Most health care providers currently take continuing education courses to acquire

knowledge in this discipline. Many have been motivated by the knowledge and interest of their patients to pursue

nutrition as a critical course of study, and to incorporate nutrition counseling into their practices.

The effects of stress and the role of vitamins, minerals (and herbs), and other nutritional variables on a

woman’s health cannot be overemphasized and must not be overlooked. Oral health, as an integral part of 

overall health, can benefit from continued research, with accompanying curriculum changes in this area.

Closing Statement

When it comes to women’s health, although we have come “a long way,” we still have a long way to go. 

There are still too many unanswered questions swirling in a sea of controversy. As we forge into the 21st century, we contemplate a new era in women’s research, with the mysteries surrounding women’s oral health issues

looming near the surface of discovery. In order to witness this imminent breakthrough, there must be continued 

and relentless commitment to the women’s health research initiative. As caretakers of this nation and the world,

women deserve better.

The gender gap in health research must be closed. There must be more emphasis placed on prevention, 

education, health promotion, and access. The physiologic, as well as the psychologic components, of health 

must receive more attention, with greater emphasis being placed on gender specificity and gender sensitivity 

in research, methodology, and design.

In order to adequately address the issues that surround the oral health status of women and minorities, 

this country must establish, maintain, and expand the pipelines that will produce black women dental 

researchers for the turn of the century and beyond.31

References

1 Sutcliffe, P., A longitudinal study on gingivitis and puberty, J Periodont Res 1972; 7:52–58.

2 Amar, S. and Chung, K.M., Influence of hormonal variation on the periodontium in women. Periodontal 2000 1994;

6:79–87.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

145

3 Gusberti, F.A., Mombelli, A., Lang, N.P., and Minder, C.E., Changes in subgingival microbiota during puberty. J Clin 

Periodont 1990; 17:685–92.

4 Steinberg, B.J., Sex hormonal alterations, In: Rose L.F., Kaye D., eds. Internal Medicine for Dentistry, 2nd Edition, 

St. Louis, MO: Mosby Publishing Co.; 1990:1073–77.

5 Rose, L.F., Sex hormonal imbalances, oral manifestations, and dental treatment. In Genco, R.J., Goldman, H.M., 

Cohen, D.W., eds. Contemporary Periodontics, St. Louis, MO: Mosby Publishing Co.; 1990:221–27.

6 Holmes, L.G., Elattar, T.M.A., Gingival inflammation assessed by histology, 3H-estrone metabolism and prostaglandin 

E levels. J Periodont Res 1977; 12:500–509.

7 Women’s Oral Health Issues, Chicago, IL, ADA Oral Health Care Series; Council on Access, Prevention, and Interprofessional Relations, 1995.

8 Massler, M., Oral manifestations during the female climacteric (the post-menopausal syndrome.) Oral Surg Oral Med 

Oral Pathol 1951; 4:1234–43.

9 Baker, R.M., Sturdee, D.W., and Davenport, J.C., Patients with burning mouth: an investigation of causative factors, 

including the climacteric and diabetes. Br Dent J 1978; 145:9–16.

10 Wardrop, R.W., Hailes, J., Burger, H., et al., Oral discomfort at menopause, Oral Surg Oral Med Oral Pathol 1989;

67:535–40.

11 Grushka, M., Clinical features of burning mouth syndrome. Oral Surg Oral Med Oral Pathol 1987; 63:30–36.

12 Weintraub, J.A., Gender differences in oral health research: beyond the dichotomous variable. J Dent Ed 1993; 57:753–57.

13 Jeffcoat, M.K. and Chestnut, C.H., III, Systemic osteoporosis and oral bone loss evidence shows increased risk factors. 

JADA 1993; 124:49–56.

14 Kribbs, P.J. Chestnut, C.H., III, Otto, S.M., and Kilcoyne, R.F. Relationships between mandibular and skeletal bone in 

an osteoporotic population. J Prosthet Dent 1989; 62:703–707.

15 Taguchi, A., Tanimoto, K., Suei Y., and Wada, T. Tooth loss and mandibular osteopenia. Oral Surg Oral Med Oral Pathol 

Oral Radiol Endod 1995 Jan; 79(l):127–32.

16 Faine, M.P., Dietary factors related to preservation of oral and skeletal bone mass in women. J Prosthet Dent 1995 Jan;

73(l):65–72.

17 Paganini-Hill, A., The Risks and benefits of estrogen replacement therapy: Leisure World. Int J Fertil Menopausal Stud

1995;40 Suppl 1:54–62.

18 Copp, D.H., Calcitonin: discovery, development, and clinical application. Clin Invest Med 1994 Jun; 17(3):268–77.

19 Sato, T. and Niwa, M., Cariostatic mechanisms of fluoride and its effects on human beings. Nippon Rinsho 1996

Jan;54(l):67–72.

20 Okano, T., Effects of essential trace elements on bone turnover—in relation to the osteoporosis. Nippon Rinsho 1996

Jan;54(l):148–54.

21 Dixon, B.M., Good Health for African Americans, 1994, Crown Publishers.

22 Carranza, Jr., F.A., Influence of systemic diseases on the periodontium, in Clinical Periodontology, 8th Edition, 

Philadelphia, PA: W.B. Saunders Company, 1996:190.

23 McNeill, C., Mohl, N.D., Rugh, J.D., and Tanaka, T.T. Temporomandibular disorders: diagnosis, management, 

education and research. JADA. 120, March 1990; pp. 253–63.
Public testimonY

146

24 Rugh, J.D. and Solberg, W.K., Oral health status in the United States: temporomandibular disorders. J Dental Ed 1985, 

49 (6): 398–405.

25 Rugh, J.D., Psychological factors in TMD in “Current Controversies in Temporomandibular Disorders.” Proceedings 

of the Craniomandibular Institute’s 10th Annual Squaw Valley Winter Seminar. Squaw Valley, CA, Jan. 23-27, 1991. 

Quintessence Publishing Co., Inc.: Chicago, 62–65.

26 Panel discussion: TMD epidemiology in current controversies. In footnote 25. p. 52.

27 Meyer, M.J., Stress and periodontal disease: a review of the literature. J New Zealand Soc Periodont 1989 Nov (68): 23–26.

28 DeMarco, T.J., Periodontal emotional stress syndrome. J Periodont 1976, 47 (2): 67–68.

29 Marcenes, W.S. and Sheiham, A; The relationship between work stress and oral health status. Soc Sci Med 1992, 35 (12):

1511–1520.

30 Zautra, A.J., Marbach, J.J., Raphael, K.G., Dohrenwend, B.P., Lennon, M.C., and Kenny, D.A., The examination of 

myofascial face pain and its relationship to psychological distress among women. Health Psychol 1995, 14 (3) 223–31.

31 Razzoog, M.E. and Robinson, E. Black Dentistry in the 21st Century. Conference proceedings. Ann Arbor, MI. 

June 23-27, 1991.

American Heart Association

Schools of Medicine and Nursing

Laura L. Hayman, Ph.D., R.N. University of Pennsylvania

Biomedical and Behavior Research Agenda

It is my pleasure to present the American Heart Association’s (AHA’s) comments focusing on the biomedical 

and behavioral research agenda for women’s health in the area of cardiovascular diseases. AHA commends the

National Institutes of Health Office of Research on Women’s Health for holding this regional meeting to update 

the “Report of the NIH: Opportunities for Research on Women’s Health.”

The American Heart Association is the nation’s largest voluntary health organization dedicated to the reduction

of disability and death from heart attack, stroke, and other cardiovascular diseases. Annually, AHA’s 52 affiliates

nationwide coordinate the activities of about 4.3 million volunteers in carrying out this mission.

Cardiovascular diseases remain a major cause of disability and the number one killer in the United States;

killing more than 954,000 Americans each year. About 13.5 million Americans, including 6.6 million under age

60, now live with the effects of heart attack. Approximately 3.8 million Americans, more than 900,000 of whom

are under age 60, suffer from the consequences of stroke, the main cause of permanent disability in the United States.

In the United States, someone dies from cardiovascular diseases every 33 seconds. In 1992, cardiovascular diseases accounted for 4.7 million years of potential life lost before age 75, followed by cancer and accidents. Recent

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

147

estimates by the National Center for Health Statistics show that the number of deaths from cardiovascular 

diseases began to rise in 1993 after years of decline.

More than one in four Americans suffer from some form of cardiovascular diseases at an estimated cost 

of $151 billion in 1996. Costs for patients with cardiovascular diseases are growing because we are treating 

disease with expensive technology, not preventing it. Moreover, there will be even more cardiovascular disability in the future because many people who have had effective treatment for coronary artery disease and 

prevention of atherosclerosis at age 40 to 60 will develop further cardiovascular diseases later in life unless 

effective prevention methods are discovered.

Cardiovascular diseases remain the number one killer of females. About 45 percent of female deaths in 

the United States are from cardiovascular diseases. Cardiovascular diseases kill almost twice as many American

females as all cancers. Heart attack, Americans’ single largest cause of death, kills more than five times as many

females as breast cancer. Of the more than 489,700 deaths from heart attack each year, more than 48 percent 

occur in females.

Importantly, the heart attack death rate for African-American women age 35 to 74 is about twice that of 

white women and three times that of women of other races. Stroke, America’s number three killer, kills twice 

as many females as breast cancer. However, until recently, heart attack, stroke, and other cardiovascular diseases 

in women had not been recognized as serious health problems, particularly by women themselves.

Women develop heart disease later in life than men. But, at any age, heart attack in women is a more deadly 

disease. Older women who have suffered heart attacks are twice as likely as men to die from them within a few

weeks. About 44 percent of women who have heart attacks die within a year, compared to 27 percent of men. 

In 63 percent of women who died suddenly of coronary heart disease, there were no previous symptoms, compared to 48 percent of men.

About one in five females suffers from heart attack, stroke, or other cardiovascular diseases. Women experience unrecognized heart attacks more often than men. After suffering a heart attack, 18 percent of women will 

suffer a stroke, compared to 9 percent of men. More than 60 percent of men and women who suffer a stroke 

die within 8 years, but long-term survivorship is higher in women than in men.

Other cardiovascular diseases are prevalent in women. More than 87,000 of fatal stroke victims are female.

This comprises 60.6 percent of fatalities from stroke. Much less prevalent are cases of rheumatic heart disease, 

an inflammatory disease that permanently damages the heart and its valves. Even in this disease, the number 

of deaths is higher in females (69.9 percent) than in males.

Despite the increasing attention being focused on health issues directly relevant to women, there remain continuing and emerging gaps in knowledge about women and cardiovascular diseases that need to be addressed.

Throughout this testimony, examples of research studies needed to answer some of the most perplexing questions 

relevant to women and cardiovascular diseases are cited.
Public testimonY

148

The major cardiovascular disease risk factors apply to women in the same manner as they do to men. There 

are, however, differences in the evolution of atherosclerosis between men and women and the risk of disease. 

These are probably related to the interaction of sex hormones and specific risk factors. Interventions should 

be tailored to sexual differences in factors such as body fat, behavior, or estrogen.

Research Needs

• What is the basic mechanism of action of both endogenous and exogenous reproductive hormones 

in the development of atherosclerosis?

• Will estrogen and estrogen-progestin combination alter the risk of coronary heart disease?

• What is the relation of estrogen to other risk factors, on vasoregulation, and other atherosclerotic processes?

• What are the metabolic effects of estrogen replacement therapy or hormone replacement therapy (HRT) 

on patients presenting with other metabolic abnormalities?

• How efficacious is HRT on cardiovascular disease in postmenopausal women?

The major risk factors for coronary heart disease (CHD) and stroke are similar for men and women: particularly high levels of low-density-lipoprotein cholesterol (LDLC), low levels of high-density-lipoprotein cholesterol

(HDLC), smoking, high blood pressure, diabetes, obesity, and physical inactivity. The gender differences appear to 

be in the distribution of risk factors, levels of risk, and risk of disease at similar risk-factor levels. Estrogens have

direct effects on the arterial wall and appear to enhance the activity of LDL receptors, resulting in lower levels of

LDLC among premenopausal women compared with men. As the estrogen level and ovarian function declines,

almost all postmenopausal women have higher LDLC levels. This increase of LDLC in older women probably

accounts for much of the increase in atherosclerosis and CHD. The prevalence of thyroid disease is higher in

women than in men; however, the relationship between clinical and subclinical thyroid disease and change 

in cardiovascular disease (CVD) risk factors, during and after menopause, is unknown.

Research Needs

• Can the rise in LDLC level and development of atherosclerosis in women be prevented?

• What changes occur in risk factors during the peri- and postmenopausal periods in nonwhite populations?

• Do differences in hormonal measures, dietary factors, and genetic characteristics influence the changes 

in risk factors and the progression of atherosclerosis?

• Why are HDLC levels higher in women after puberty compared with men? Are they determined solely 

by sex-steroid metabolism?

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

149

Weight gain occurs between 30 to 50 years of age in women; in men it usually occurs between 20 to 40 years

of age. The distribution of body fat is different in women than in men. For example, more central obesity exists in

black women than in white women, but body mass index and waist:hip ratio predicted cardiovascular death only

in white women. Gender or racial differences in HDLC levels among women is partially a result of individual differences in obesity, distribution of body fat, insulin, glucose, metabolism, obesity-related effects on Lp(a) and hepatic

lipase, insulin resistance, and fatty acid metabolism.

Research Needs

• How do the patterns of obesity and fat deposition relate to cardiovascular disease in women?

• What are the determinants of weight gain in women?

• What are the most effective approaches to preventing obesity among minorities?

• Is there an association between number of pregnancies and weight gain?

Mortality rates for heart disease are higher among women with less than 8 years of schooling. In 1960, the

mortality rate for these women was 80 percent higher than among women who had some college education. These

differentials exist 20 to 30 years later. In 1988, 40 percent of families were dual-worker families in which both husband and wife worked; compared with 9 percent in 1940. There has been a dramatic increase in divorce and one

parent families. Social environment and income, as well as access to and quality of medical care, play a direct role

in risk factor levels.

Research Needs

• What are the roles of poverty, work environment, and family responsibilities in the etiology of CVD 

risk factors or events in women?

• What are the psychosocial factors related to CVD in women?

• What are specific CVD risk factors in women?

• Do hormonal or psychosocial factors explain why childless women have a higher risk of sudden death?

• What is the relationship of pregnancy history to CHD risk factors?

• What are the associations between social factors and risk of CHD in women?

Recommendations for research from the National Heart, Lung, and Blood Institute Task Force on Sociocultural

Factors in Cardiovascular Disease in Women should be reaffirmed. The task force emphasized the importance of

developing valid and reliable measures of work and family exposures for women, rather than using measures 

from studies of men. Measures are also needed to record women’s situations in terms of socioeconomic positions,
Public testimonY

150

occupation, family life, psychosocial demands, social support, and discrimination. Certain characteristics among

premenopausal women provide natural experiments for studying the interrelationship of lifestyles, obesity, hormones, and coronary artery disease. Women who have polycystic ovary syndrome have obesity, more androgenic

sex-steroid hormones profiles, insulin resistance, amenorrhea, and high blood estrone levels primarily from the

adrenal gland. Women who have this syndrome generally have low HDLC levels, but it is not clear whether they 

are at increased risk of atherosclerosis, whether treatment of obesity modifies clinical aspects of the syndrome 

and risk factors, and what changes in risk factors and CHD risk factors occur with aging. The relationship of 

premenopausal hormone patterns and CHD has not been studied adequately.

About 50 percent of African-American women have a hysterectomy prior to the time of natural menopause. 

A leading cause of hysterectomy in these women is uterine fibroids. Fibroids may be part of a syndrome of obesity,

elevated estrogens, hypertension, diabetes, and subsequent risk of vascular disease, especially among AfricanAmerican women.

The use of luteinizing hormone-releasing hormone (LDRH) agonists and antagonists in the treatment of 

uterine fibroids effectively cause oophorectomy. Their use provides a natural experiment for evaluating the 

acute effects of chemical oophorectomy on HDLC, LDLC, and clotting factors in subgroups of women.

Women are more likely than men to die of stroke. Twice as many black women die of stroke in all age 

groups. Multiple pregnancies may increase risk of cerebrovascular disease through the mechanism of insulin 

resistance. Diabetes triples the risk of stroke in women. The increased risk of subarachnoid hemorrhagic and

ischemic stroke in women who smoke may be reversed in 2 to 4 years after smoking ceases.

Research Needs

• Are there other potentially reversible stroke risk factors in addition to smoking?

• Why is there a later onset of stroke, other cardiovascular diseases, and coronary heart disease in women 

versus men?

• What is the extent of various venous disorders seen predominantly in women? Can they be prevented?

• What is the effect of estrogen therapy on the reversal and progression of stroke and peripheral 

vascular disease?

Other cardiovascular disorders that particularly affect women cause inflammatory microvascular and macrovascular diseases. The most important of these is systemic lupus erythematous (SLE). Coronary heart disease is

higher in these patients. While part of the excess death is probably related to treatment, corticosteroid drugs, and

renal disease, it is possible that the autoimmune inflammatory process of SLE affects the coronary and cerebral

arteries, thus increasing risk of CHD and stroke. SLE should be considered as providing a natural experiment 

for measuring the effect of autoimmune disease and inflammatory cytokinins on the development of CHD and 

atherosclerosis, as well as dysfunction of the heart muscle which can cause serious arrhythmia. The relationships 

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

151

of physical activity and cardiorespiratory fitness with hemodynamics, risk-factor levels, and behavioral studies 

need to be assessed in pre- and postmenopausal women and minority populations.

Insulin-dependent diabetes mellitus is an important cause of premature CVD among young men and women

less than 45 years of age. CVD is especially high among premenopausal women with insulin-dependent diabetes

mellitus who smoke cigarettes. Studies are needed to ascertain why diabetes is one of the few conditions that 

greatly reduces the favorable CVD status of premenopausal women. Data are needed on efficacy of medical and

revascularization therapy, and on exercise rehabilitation for CHD failure and stroke.

The apparent differences in presentation of CVD and response to intervention, which may be complicated 

by menopausal status in women compared with men, should be studied.

Additional Research Needs

• What are the qualitative aspects of angina in women versus men?

• Do women have subtle asymptomatic limitations in coronary reserve?

• Are there gender-related differences in silent ischemia in coronary artery disease?

• How is response to diet modification affected by age, status, hormone replacement therapy, and 

baseline lipid lipoprotein levels?

• What are the outcomes of antihypertensive therapy by gender?

Unique scientific and logistical issues must be addressed in any randomized trial of CVD in women. These

relate primarily to hormonal differences, psychosocial variables, and possibly anatomical factors peculiar to women.

Our ability to combat cardiovascular diseases correlates directly with the level and quality of overall support

for basic and clinical research and prevention efforts.

Since 1949, the American Heart Association has invested almost $1.4 billion in research to increase knowledge

about cardiovascular diseases. The size of this financial commitment makes AHA second only to the federally sponsored National Institutes of Health in the amount devoted to cardiovascular research. Although AHA will continue

to commit increased resources toward research, larger efforts by the Federal Government are essential to win the

battle against cardiovascular diseases. A significant increase in funding for federal biomedical research is critical.

In constant dollar from FY 1985 to FY 1995, the budget for the National Institutes of Health increased by 

31 percent compared to a 4.8 percent decrease for the National Heart, Lung, and Blood Institute’s Heart Program.

Since FY 1992, funding for National Institute of Neurological Disorders and Stroke-supported stroke research

increased by less than 1 percent in constant FY 1985 dollars. Yet, an overwhelming number of respondents in a
Public testimonY

152

1996 nationwide American Heart Association-commissioned survey support increased funding for heart research

(79 percent) and stroke research (77 percent).

Chronic underfunding of heart and stroke research has discouraged young people from entering the field. 

This is dramatically reflected by statistics showing that in 1994 there were 63 percent fewer research grants 

awarded by the National Heart, Lung, and Blood Institute’s Division of Heart and Vascular Disease, to individuals

under the age of 40, than there were in 1994. In absolute numbers, this is only 123 research grants currently to

doctors and scientists under the age of 40, approximately 1 per medical school, in the whole area of heart and vascular disease. As a result, this nation has lost, or is losing, a whole generation of cardiovascular disease researchers.

Sexually Transmitted Diseases Branch

Penelope J. Hitchcock, D.V.M. National Institute of Allergy and Infectious Diseases

Adolescents and Sexually Transmitted Diseases

This paper presents a brief overview of sexually transmitted diseases (STDs), including acquired immunodeficiency syndrome (AIDS), in adolescent populations. Using the framework of a mathematical model (which 

considers how, why, and whether an infection spreads within a population), the epidemic of STDs among adolescent populations is considered. The unique aspects of adolescent behavior, adolescent biology, and the social

context of adolescents’ lives are highlighted.

Magnitude of the Problem

The majority of young people have sexual intercourse for the first time in their teens.1 A recent report indicates that more than half of women and almost three-quarters of men have had sexual intercourse by their 18th

birthday.2 Two recent studies have provided data indicating that sexual activity among teenagers is increasing.3,4

Other studies have also documented that adolescents and young adults are inconsistent users of male condoms.5

Given these behavioral factors, the implications for risk of sexually transmitted diseases (STDs), including

human immunodeficiency virus (HIV) infection, are undeniable and are supported by the data trends for STDs in

teen populations. Recently the Centers for Disease Control summarized reported AIDS cases in teenagers for the

first 6 months of 1995. The cases increased 524 percent compared to 1994. Furthermore, if one assumes an incubation time of 8 years from the time of HIV infection to the onset of AIDS, 20 percent of all persons with AIDS were

infected as teenagers.6 A closer look at the demographics of the new AIDS cases reveals that gay teens account for

most of these. Arguably this trend represents cases among new susceptibles in a larger population that has been 

at high risk for HIV infection since the beginning of the AIDS epidemic.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

153

If other STDs are considered, however, a larger picture of high-risk adolescent populations emerges. In the

United States, it is estimated that 12 million incident cases of STDs occurred in 1994; the majority of these cases

are in young adults, with an estimated 3 million occurring in teenagers. Age- and gender-specific rates are depicted

for two bacterial STDs, gonorrhea and chlamydial infection. Cases of gonorrhea are found among populations of

low socioeconomic status (SES) in urban and rural areas of the United States. The highest rates are seen in young

men 20 to 24 years of age and in teenage girls 15 to 19 years of age.7 There is enormous heterogeneity, however,

depending on the geographic area, with the highest U.S. rates reported from the District of Columbia, where one 

in ten 10- to 14-year-old boys was infected.8

The national picture of chlamydial infection is harder to bring into focus for several reasons: (1) not all 

regions are reporting data yet; (2) not all regions have the resources to implement chlamydial control programs

now recommended by the CDC; and (3) new diagnostic methods have increased our ability to identify patients.

Two trends are clear, however. First, rates are highest in 15- to 19-year olds regardless of SES. Second, where

screening and treatment programs are implemented, rates among teens have dropped.

For the other viral STDs, the situation is similar to that for gonorrhea and chlamydial infection, although the

trends have more serious implications for transmission. Because these viral infections are incurable, each incident

case becomes a prevalent case. Furthermore, any STD, whether it is theoretically curable with treatment or not, 

can accumulate in the population if the patient is not effectively treated.

The Reproductive Rate of Infection — How It Applies to Adolescent Populations and Sexually Transmitted Diseases

Early on in the AIDS epidemic, May and Anderson took a mathematical view of the potential for HIV infection

to spread through a population.9,10 Although the mathematical proofs are complicated, the basic principles of the

formula that they derived are not. They tried to identify how fast an infection can “reproduce itself” or the speed

and extent to which an infection can move through a population. They recognized that there are three essential

components of any epidemic: (1) the infectious organism or the “bug;” (2) the biologically susceptible host; and 

(3) the behaviors of both. They then determined the mathematical relationship among the essential components.

The simplified version of the formula is Ro=cd. Ro is the reproductive rate of infection; o is the infectivity rate: in

other words, how easily the infection is transmitted from one host to the next; c is the rate at which new partners

are chosen, as well as the characteristics of the partner; and d is the duration of the infection: in other words, once

established, the infected person may be “infectious” for a long or short time. The duration would reflect whether

the infection is self-limiting, or curable with treatment, or incurable. Subsequently, this approach has been used 

to look at other sexually transmitted diseases and the behavioral risk factors associated with transmission and

development of long-term consequences or sequelae.11,12

Within each factor of the equation there are biological and behavioral risk factors that have been causally 

associated with increased risk of transmission/acquisition. In addition, a number of associations, or markers of 

risk, have been identified. With risk markers, however, a direct causal link to STDs/HIV infection has not been

demonstrated. The interested reader is referred to the paper by Padian and co-workers for a more complete 
Public testimonY

154

discussion of risk factors versus markers.13 Among the biological and behavioral risk factors/markers that alter 

the risk of STDs, those that are of particular concern in adolescent populations are highlighted.

Infectivity Rate

Within the risk factors/markers, 9 of 13 represent particular risks for adolescent populations. Several merit 

particular comment. Genetic susceptibility: the hormonal changes of puberty and arguably those induced by some

hormonal contraceptives are manifested by changes in the epithelial surface of the cervix. The surface of the epithelium is covered with a mucous coat; the tissue surrounding the opening to the uterus, the cervical os, is covered

with stratified squamous epithelium. Close to the cervical os, the tissue changes into columnar epithelium; the

small zone of transition is dark pink. When we look again at a healthy cervix, the zone of transition is much larger

because of hormonal influences. This enlarged transition zone, known as the zone of ectopy, is the site of attachment and establishment of infection in gonorrhea and chlamydial infection. The larger the zone of ectopy in the

cervix of the adolescent, the larger the target for these infections.14,15 Sexual practices: in some adolescent populations anal intercourse is practiced in order to “preserve virginity” and as a method of birth control. Rectal transmission of HIV infection is facilitated by trauma and direct contact with blood and by receptor-mediated uptake 

of the virus owing to CD4-like receptors on rectal epithelial surfaces.16 Contraceptive method: as mentioned above,

hormonal methods of contraception may alter susceptibility to infection because of alteration of tissue architecture,

or changes in the character and amount of mucus, or changes in pH.17

Rate of Partner Change and Partner Characteristics

Within the risk factors/markers, four to five have special implications for adolescents. Number and types 

of partners: given that adolescents begin having sexual intercourse at an early age, the likelihood is that for many 

the lifetime number of partners will be large. When looking at the sexual behavior of 20 year olds, it is estimated

that one-third have had two to five lifetime partners by this age.3,18

The significance of lifetime partners can be best appreciated with a simple arithmetic problem. Keeping 

in mind the concept of incurable viral STDs accumulating in the population and two assumptions: (1) that 

adolescents practice serial monogamy (i.e., one partner at a time in series); and (2) that all adolescents in a 

given population have the same partner acquisition rate, how many exposures, real and phantom (partners 

of partners), are represented in an adolescent’s life between the ages of 15 and 24 if:

• the adolescent has sexual intercourse for the first time at 14;

• each relationship/partner lasts 1 year; and

• they have a new partner each year?

In the 9 years, they will have nine real partners. In terms of incurable viral STDs, where both the real and the

phantom partners are relevant, they have been exposed to more than 500 partners. The significance of exposure 

to phantom partners is reflected in recent studies of human papillomavirus infection; high infection rates were

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

155

observed in college-aged women during their first year of sexual activity. An attack rate of 25 percent was seen

among women in Seattle; interestingly the average number of partners for the first year of sexual activity was 

fewer than two.19

Duration of Infection

Aside from the characteristics of the infectious agent, all of these risk factors/markers represent particular 

problems for adolescent populations. Of the seven infections that are solely or primary sexually transmitted, four 

are treatable/curable bacterial infections (chlamydial infection, gonorrhea, syphilis, and chancroid); one is a treatable/curable parasitic disease (trichomoniasis); and three are incurable viral infections (human papillomavirus 

infection, genital herpes, and HIV infection). For the most part, all of these infections can and do manifest without

symptoms.15 As a result, people without symptoms, with unrecognized symptoms, or with symptoms so indolent 

as to preclude health care-seeking behavior represent a continued source of infection for their partners.

In addition to the absence of symptoms, the lack of access to health care, the policies of parental and partner

notification, the expense of health care, and the failure to accept and comply with treatments are some of the 

factors that increase the duration of infection.

Distribution of STDs, Including HIV Infections, in the Population

For some infections, virtually all cases are found within populations that are at high risk. As discussed earlier,

the demographics of those populations include low SES, rural or inner-city residency, and partner number. In the

case of chlamydial infection, genital herpes, and human papillomavirus infection, the diseases are “clustered” to 

a lesser extent and are more evenly distributed in the population.

Although AIDS cases in the United States are currently clustered in high-risk populations, there is no reason,

based on the models that have been used to analyze the epidemic, why they will remain clustered. HIV infection

has a number of characteristics that contribute to sustained presence within a population:

• HIV is transmitted sexually, a behavior that is required to reproduce our species;

• HIV infection is an asymptomatic disease; the host is infectious for many years;

• the viral genome becomes a part of the host’s genome and can remain “invisible” for a long time; and

• HIV lives within the body’s disease-fighting system, making vaccine development efforts extremely difficult.

Because we neither screen for nor report HIV infection in a systematic way, we are forced to extrapolate HIVinfection trends from AIDS cases. Unfortunately, the development of AIDS is the terminal phase of the infection,

and AIDS cases do not reflect trends in HIV-infection rates today. Some argue that the epidemic has leveled off and

that we are experiencing the saturation of susceptibles in high-risk populations. This could be the explanation for

the data; the other possibility is that we are experiencing the end of the first phase of the epidemic, during which

high-risk populations became infected at very high rates. During the plateau that separates phase 1 and phase 2,
Public testimonY

156

the infection moves clandestinely into the general population, and then the AIDS case rates would begin to 

climb again. This time, however, the slope would be less steep, since the cases would be occurring in lower-risk 

populations.20,21 The possibility that adolescent populations and STDs (chlamydial infection and genital herpes)

could provide the messenger and the opportunity for HIV infection to become more broadly distributed in the 

population is raised in studies of adolescent populations that are geographically and socially juxtaposed to 

high-risk populations.22–25

Whether we will be able to aggressively and effectively address the implicit research and program needs 

and opportunities that must be met in order to prevent the spread of HIV infection into adolescent populations

remains to be seen.26 The risk factors/markers represent a very formidable research agenda: basic biomedical and

behavioral research, applied research, and clinical and operations research. Furthermore, more support for clinical 

services for adolescents in a variety of settings is implicit in an effective approach to prevention and control.

References

1 Leigh, B., Morrison, D., Trochi, K., et al. Sexual behavior of American adolescents: Results from a U.S. National Survey. 

J Adolesc Health 15:117–25, 1994.

2 Kost, K. and Forrest, J.D. American women’s sexual behavior and exposure to risk of sexually transmitted diseases. 

Fam Plann Perspect 24:244–54, 1992.

3 Trends in sexual risk behavior among high school students—United States, 1990, 1991 and 1993. Morbidity and 

Mortality Weekly Report 44:7:124–26, 1995.

4 Costa, F.M., Tessor, R., Donovan, T.E., et al. Early initiation of sexual intercourse: The influence of psychosocial unconventionality. J Res Adolescence 5:93–121, 1995.

5 Peterson, L.S. Contraceptive use in the United States: 1982–90. Advance data from Vital and Health Statistics; No. 260.

Hyattsville, MD: National Center for Health Statistics, 1995.

6 HIV/AIDS Prevention Facts about Adolescents and HIV AIDS. December 1995. Centers for Disease Control.

7 STD Surveillance 1994, Centers for Disease Control.

8 Berman, S. Talk presented at Adolescents and STDs meeting, sponsored by NIAID, Annapolis, 1995.

9 Anderson, R.M., May, R., and Anderson, R. Transmission dynamics of HIV infection. Nature 326:137–42, 1987.

10 Anderson, R.M. The epidemiology of HIV infection: Variable incubation plus infectious periods and heterogeneity 

in sexual activity. J R Stat Soc 151:66, 1988.

11 Padian, N.S., Shiboski, S.C., and Hitchcock, P.J. Risk factors for acquisition of sexually transmitted diseases and development of complications. In: Wasserheit, J.N., Aral, S.O., Holmes, K.K., and Hitchcock, P.J. (eds.). Research Issues in Human

Behavior and Sexually Transmitted Diseases in the AIDS Era. Washington, D.C.: American Society for Microbiology, 1991.

12 Anderson, R.M. The transmission dynamics of sexually transmitted diseases: The behavioral component. In: Wasserheit,

J.N., Aral, S.O., Holmes, K.K., and Hitchcock, P.J. (eds.). Research Issues in Human Behavior and Sexually Transmitted 

Diseases in the AIDS Era. Washington, D.C.: American Society for Microbiology, 1991.

13 Padian, N.S., et al. The effect of number of exposures on the risk of heterosexual HIV transmission. J Inf Dis 161:

883–88, 1990.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

157

14 Ehrhardt, A.A. and Wasserheit, J.N. Age, gender, and sexual risk behaviors for sexually transmitted diseases in the United

States. In: Wasserheit, J.N., Aral, S.O., Holmes, K.K., and Hitchcock, P.J. (eds.). Research Issues in Human Behavior and 

Sexually Transmitted Diseases in the AIDS Era. Washington, D.C.: American Society for Microbiology, 1991.

15 Holmes, K.K., Mardh, P.A., Sparling, P.F., et al. Sexually Transmitted Diseases. New York: McGraw–Hill, 1990.

16 Levy, J.A. The transmission of HIV and factors influencing progression to AIDS. Am J Med 95:86–100, 1993.

17 Speross, L., Glass, R.H., and Kase, N. (eds.). Clinical, Gynecologic, Endocrinology and Infertility, 5th edition. Baltimore:

Williams & Wilkins, 1994, pp. 183–230, 321–360.

18 National Survey of Family growth. 1988.

19 Koutsky, L.A., et al. Underdiagnosis of genital herpes by current clinical and viral isolation procedures. New Engl J Med

326:1533–39, 1992.

20 Blower, S.M. Exploratory data analysis of three sexual behavior surveys: Implications for HIV-1 transmission in the UK.

Philos Trans Royal Soc London, B Biol Sci, 287:33–51, 1993.

21 Blower, S.M. and van Griensven, G.J. Effect of differential mortality on risk behavior change in cohort studies. J Acquir

Immune Defic Syndn 12:1364–67, 1993.

22 Holmberg, S.D., Stewart, J.A., Gerbes, A.R., et al. Prior herpes simplex virus type 2 infection as a risk factor for HIV 

infection. JAMA 259:1048–50, 1988.

23 Hook, III, E.W., Cannon, R.O., Nahmias, A.J., et al. Herpes simplex virus as a risk factor for human immunodeficiency 

virus infections in heterosexuals. J Tropical Dis 165:251–44, 1997.

24 Laga, M., Manoka, A., Kivuvu, M., et al. Nonulcerative sexually transmitted diseases as risk factors for HIV-1 transmission 

in women: Results from a cohort study. AIDS 7(1):95–102, 1993.

25 D’Angelo, L.J., Getson, P.R., Luban, N.L., and Gayle, H.D. Human immunodeficiency virus infection in urban adolescents:

Can we predict who is at risk? Pediatrics 5:982–86, 1991.

26 Hitchcock, P. Screening and treatment of sexually transmitted diseases: An important strategy for reducing the risk of HIV

transmission. AIDS Pat Care 10(1):10–15, 1996.

Lisa Kaeser, J.D. The Alan Guttmacher Institute

The Alan Guttmacher Institute is a not-for-profit public education and public policy organization that focuses 

on reproductive health. This testimony addresses the needs in one area of reproductive health, that of further

research into successful use of contraceptive methods to prevent unintended pregnancy.

An increasingly greater portion of women’s lives is spent attempting to control their fertility. During the last

century, both puberty and sexual initiation have moved to earlier ages. The interval for women between puberty 

and marriage has risen and most married women choose to delay or limit the number of children they have.

Women today spend three-quarters of their reproductive lives, from menarche to menopause, trying to avoid 

becoming pregnant.
Public testimonY

158

Unintended pregnancies, and their outcomes, carry significant health and social consequences for both the

woman and, if she carries to term, the child. However, in 1988, more than 3 million unintended pregnancies

occurred in the United States. If contraceptives were always used perfectly by everyone who wanted to avoid

becoming pregnant, the rates of unintended pregnancy in the United States would be a fraction of where they 

now stand. Current wisdom, which provides a major rationale for continued research on new contraceptives, 

points to difficulties women and men have integrating correct and consistent use of current methods into their

daily lives. Clearly, a better understanding of the needs of women and their partners who wish to use contraception is needed, both to increase the use of currently available methods and for the development of new ones.

Specifically, a better understanding is needed of what causes people (1) to delay initiating use of a contraceptive method once they become sexually active, (2) to permit gaps between periods of contraception use, 

or (3) not to use their chosen method as well as possible.

Obstacles that may prevent couples from using contraceptives when they are at risk for unplanned pregnancy

include: (1) women not initiating the use of, or stopping the use of, contraceptives due to a lack of accurate information or fear of side effects, and (2) access to and payment for family planning services. Research is needed on

what may contribute to using contraceptives. Such research may focus on: a woman’s ambivalence about childbearing, common mistakes in the use of contraceptives, concerns about disease that prevent women from using 

the most effective contraceptive method(s), and the impact of education and counseling on the successful use 

of contraception.

Although contraceptives have been used for decades, many questions remain unanswered. While answers 

to these questions will not necessarily “solve” the dilemma of unintended pregnancy in the United States, if the

answers can assist in reducing the rates of unintended pregnancy, a substantive contribution to women’s health 

can be made.

Virginia T. Ladd American Autoimmune Related Diseases Association

Autoimmunity is a debilitating condition in which the immune system attacks the body’s own tissues or cells.

The condition is the root cause of more than 80 serious and chronic diseases, including connective tissue diseases

(lupus); diseases involving the joints (rheumatoid arthritis); skin diseases (scleroderma); neuromuscular diseases

(multiple sclerosis); and endocrine diseases (Graves disease). The American Autoimmune Related Diseases Association (AARDA) is the nation’s only organization dedicated to raising the awareness of early warning signs of

autoimmune diseases and promoting collaborative research efforts to cure autoimmunity.

During its recent Health Women 2000 conference in Washington, the Office on Women’s Health recognized

that autoimmunity is largely a women’s health problem, representing approximately 75 percent of all autoimmune

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

159

patients. ORWH has a great opportunity to increase the visibility and focus on autoimmunity as a common cause 

of diseases that disproportionately affect women.

For many women, getting a proper diagnosis for an autoimmune disorder is as difficult as the disease itself.

Misdiagnosis and late diagnosis, and their associated problems, are major concerns of AARDA. Several factors contribute to improper diagnosis, which delays appropriate treatment. For instance, symptoms of autoimmunity vary

and they may come and go. Also, symptoms are often difficult for a woman to describe precisely to her physician.

The multiplicity of symptoms and affected body systems may cause the patient to undergo a series of unsuccessful

tests as specialists attempt to establish a diagnosis. The difficulty in identifying symptoms may result in a physician

not taking the patient’s complaints seriously. A survey AARDA conducted found that over 65 percent of patients

with autoimmune diseases are labeled hypochondriacs in the earliest stages of their illness. The psychological

impact of late diagnosis can be devastating.

The problems of timely recognition and diagnosis results from the fragmented way in which the medical 

community approaches autoimmunity. Unlike cancer, autoimmunity has yet to be embraced by the medical community as a category of disease. Discovering the root cause for all autoimmune diseases depends on basic research.

ORWH is well positioned to take a leading role in organizing a concerted education and research campaign to

improve recognition of, and early testing for, autoimmune diseases and in promoting basic research into autoimmunity. Basic research will yield information that benefits the treatment and diagnosis of all autoimmune 

diseases and represents the most promising approach to finding a cure.

AARDA desperately seeks to bring a national focus to autoimmunity. We feel that ORWH, perhaps more 

than any other office or institution, can substantially improve our country’s approach to this critical women’s 

health issue. We strongly urge ORWH to push for collaborative efforts to conduct basic research that would bear

fruit for all autoimmune diseases, rather than continuing to focus more narrowly on individual diseases. It is

through combined research that we will be able to diagnosis, treat, and ultimately cure this debilitating disorder.

Dorothy Mann Family Planning Council

The Family Planning Council is a private, nonprofit organization which receives all Title X federal family 

planning funds for Philadelphia and its four surrounding counties. With these and other public funds, the Council

subcontracts with 24 local health care organizations. The typical Title X family planning patient seen in any one 

of our programs is an African-American women between the ages of 20 and 29. She is poor, and the family planning clinic offers the basic health care she needs to stay in school, keep a job, or pursue vocational training.

Gaps in knowledge about women’s health involves reproductive issues. Specifically, the need for knowledge 

is greatest in the areas of pregnancy and disease prevention. According to the Institute of Medicine, the rate of
Public testimonY

160

unintended pregnancy among American women is disgracefully high, with almost 60 percent of all pregnancies

unintended. Regardless of a woman’s economic level, unintended pregnancy affects every sphere of a woman’s life,

threatening her physical well being, her emotional stability, and her ability to obtain or keep gainful employment.

The high rate of unintended pregnancy among American women should be a clarion call to the health care and

medical research establishments and the pharmaceutical companies to devote the resources necessary to significantly reduce this statistic. Contraceptive research is needed to find methods that offer the full range of protection

against unplanned, unwanted pregnancy as well as debilitating, highly contagious diseases.

A number of other questions also have important implications for women’s health. These questions relate 

to HIV/AIDS; the reproductive health care needs of premenopausal, perimenopausal, and postmenopausal 

women; risks for unintended pregnancy, sexually transmitted diseases; cancer; education about the use of 

hormone replacement therapy; and infant mortality among African Americans.

Unlike with research and medical service delivery for cardiovascular disorders, breast cancer, endocrine disorders, and Alzheimer’s disease, Congress dictates the methodology, scope of research, and medical procedures 

in the area of reproductive medicine. Currently, Congress is considering legislation that will require the written 

consent of parents for any research that involves adolescents. Although strict consent requirements and protection

of human subject regulations exist, Congress wants to curtail research that examines any research related to adolescent sexual health. In this way a political agenda takes precedence over the quest for knowledge and understanding.

It is easier to allocate public and private resources to politically palatable research in such areas as breast cancer and

osteoporosis than it is to devote the necessary resources to other equally important areas of women’s health that are

related to sexuality. While adding women to clinical trials and other research efforts is necessary and important, it

will not matter if political agendas dictate subject, method, and outcome. In women’s health research, it is important to invest in and examine controversial issues of sexuality and reproduction. It will take courage to expose and

stand up to powerful political forces that would otherwise impede this research.

Rita M. May Sjögren’s Syndrome Foundation, Inc.

Autoimmune and rheumatoid diseases are the stepchildren of the women’s health initiative. Despite the fact

that diseases such as multiple sclerosis, scleroderma, and Sjögren’s syndrome profoundly affect women, they are 

not considered topics of high priority on any of the women’s health agendas.

Medicine and science favor the so-called “interesting questions.” They attract the greatest scientific intellects,

are well funded, and reflect social priorities. For example, AIDS, a comparatively rare disorder, was successfully

transformed from an interesting scientific problem into a well-funded institution. During the 14-year period from

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

161

1981 to 1995, about a half-million Americans were diagnosed with AIDS compared to more than 37 million Americans who suffered from other autoimmune diseases. The drive to find a cure for AIDS has made NIAID the third

most heavily funded NIH institute, while funding for more widespread autoimmune diseases has declined.

Probable reasons for the lack of interest and minimal funding include the following:

• the sheer number of autoimmune diseases and the dearth of clear diagnostic guidelines;

• the association of autoimmune diseases with aging but not death, and the subsequent lack of urgency 

to discover treatments and cures; and

• the higher prevalence of autoimmune disease among women than men.

Sjögren’s syndrome presents an excellent example of the ignorance, invisibility, and unpopular nature of

autoimmune and rheumatoid diseases in general, and within the scientific and women’s health communities in 

particular. Although it affects 2 to 4 million Americans — 90 percent of whom are women — it is one of the least

diagnosed. Moreover, none of the most likely NIH institutes — NIAMS, NIAID, NEI, nor NIDR — has sponsored

epidemiological studies directed at Sjögren’s syndrome. Indeed, the chances for even highly sophisticated audiences

to have heard of Sjögren’s (much less be able to spell it!) are low, sadly demonstrating the lack of interest in these

diseases and in the women who suffer from them.

I ask that NIH dedicate research monies to autoimmune disease research and conditions affecting the aging 

as well as diseases affecting reproductive issues and youth.

Margaret K. McLaughlin, Ph.D. Magee-Women’s Research Institute

At the Magee-Women’s Research Institute, we believe that increasing the number of women scientists and 

facilitating their careers will result in more women’s health researchers.

This task requires a concentrated effort to increase public awareness about the significance of scientific

research. We believe that our outreach work will result in greater awareness of, and interest in, science and 

research on women’s health. Our efforts target high school and college students — both boys and girls, men 

and women. We host tours of the Institute, provide hands-on demonstrations of our work, sponsor a summer

research volunteer program, and provide stipends for college students studying the sciences. Some programs 

we target directly at young women. For example, we have a special relationship with a local girls’ high school 

and pay special attention to women’s colleges in our geographic area.
Public testimonY

162

At a more advanced level, we recognize that nursing is a severely underutilized source of women in science.

The Institute pays part of the salary for the director of nursing research at Magee-Women’s Hospital, where she 

educates nursing staff about research opportunities and recruits participants for Institute projects.

Retention, as well as recruitment, is critical to ensuring there are women in science. We feel that it is important 

to not lose sight of the problems that face men and women embarking on careers in scientific research. It is critical

that they understand the gender issues in research and are supported in their efforts to advance in the areas in

which they choose to specialize. Our proactive mentoring program is a crucial tool for assisting new researchers 

in overcoming these challenges and encouraging them to remain in the field.

We are proud of these efforts and hope others can learn from them in their quest to demonstrate and increase

public awareness about the joys and excitement of careers in science.

Allegheny University Hospitals

Powers Peterson, M.D. American Society of Clinical Pathologists

New developments in the area of women’s disease research and diagnosis, as well as the increased participation of women in biomedical careers, have been encouraging. However, more needs to be done if progress 

in the field of women’s health is to continue successfully into the 21st century.

Women currently comprise a large sector of the health care community. In 1994, women represented 

18 percent of all physicians in the United States. In the field of pathology, women comprised 24 percent of 

all pathologists in the country and 83 percent of the medical technologists certified by the American Society 

of Clinical Pathologists (ASCP) in 1995.

ASCP has been indirectly involved in efforts to recruit, retain and advance women in biomedical careers on 

a project-to-project basis. ASCP volunteers have been involved with educational projects, funded through the Title

VII Allied Health Project Grant Program, designed to enhance recruitment and retention of minority and disadvantaged populations. One model program utilizes the mentor concept and promotes the recruitment and retention 

of medical technologists through a four phase design that begins with career awareness activities for elementary 

and middle school students. Similar projects could be established for the recruitment and retention of women 

in biomedical careers.

Offices of Women in Health Professions on some medical school campuses provide another successful model.

These offices serve as excellent resource centers and bring together a variety of health care providers, both physician and nonphysician, to address issues related to women in biomedical careers. In addition, ASCP offers print

and video materials describing careers in laboratory medicine; maintains a scholarship fund for individuals wishing

to pursue such careers; and has a Career Recruitment Network, which provides mentors for those seeking to enter

the field of laboratory medicine.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

163

Although progress in addressing women’s health issues is being made, a stronger infrastructure needs to 

be established to identify and respond to new challenges for women’s health. Adequate funding is imperative to

explore further and better understand the implications for women regarding new advances in disease research 

in the areas of cancer, heart disease, and HIV and other infectious diseases. In particular, more must be done to

research further and investigate various aspects of women’s health and coronary heart disease. In addition, women’s

health care could be better served as a comprehensive discipline that uses a combination of medical perspectives 

in patient care. The future of women’s health research also needs to include a focus on emerging infectious diseases

including chlamydia, sexually transmitted human papillomavirus, and Group B Streptococcus. Despite the continued threat of emerging infections, support for applied research and control efforts has declined during the past

decade. For this reason, it is critical that women’s health research, and the resources to conduct such research,

focus on addressing emerging infectious diseases.

Marj Plumb, M.N.A. National Center for Lesbian Rights

The National Center for Lesbian Rights (NCLR) was founded in 1977 as a lesbian, feminist, multi-cultural 

legal and public policy resource center. In the past 4 years, NCLR launched several pioneering programs in order 

to better serve all members of the lesbian community. One project was our Lesbian Health Project, which supports

grassroots organizing and advocates for equitable public policies regarding health care for lesbians. Since this project’s inception in 1993, NCLR has become a leader in helping build what is now a vital and growing national 

lesbian health movement. Through this project, NCLR publishes a Lesbian Health Issues Newsletter, a Lesbian 

Health Bibliography, and other publications of interest on the issue of lesbian health and parenting.

The purpose of my testimony is to begin to articulate a common understanding of what lesbian health issues

are, to share the successes of the modem lesbian health movement in order to provide encouragement for continued inclusion of lesbian health issues, and to present a universal list of recommendations that can be enacted by

public health departments, health agencies, research institutions, and medical schools.

Introduction

Few would disagree that the lesbian health movement is at a unique moment in time. We have a community

more interested in health issues than ever before, more knowledgeable about the health system and health terminology, and we have greater access to the federal health department than under any other administration. This 

convergence of experience, access, and visibility creates the possibility for us to make significant advances in the

development of a health care system truly responsive to lesbian and bisexual women’s needs.
Public testimonY

164

Throughout the country, we have seen that our individual organizing efforts to provide services — often by 

lesbians for lesbians — is effective and powerful. Local grassroots groups have developed and implemented lesbian

and bisexual women’s health needs assessments and begun strategic planning for program development in many

communities. Some of these efforts have resulted in new organizations specifically formed to address lesbian health.

Some efforts have resulted in forming lesbian health projects within gay and lesbian organizations or even mainstream health organizations. But we can’t and shouldn’t do it alone. There needs to be lesbian and bisexual women’s

voices in the debates over changes in Medicaid and Medicare, in the movements to create national health reform, 

in the development of research agendas, in advocating for changes in medical school curriculum, and in setting 

priorities within public health departments.

Lesbian Health Overview

Women’s health issues are defined by the Public Health Service (in the 1991 Action Plan for Women’s Health)

as “diseases or conditions which are unique, more prevalent, more serious, and for which risk factors and interventions are different for women or some subgroups of women.” It is within this framework that I discuss lesbian health

issues: the diseases, conditions, risk factors, and interventions that impact lesbians, as a subgroup of all women;

there are distinguishable factors attributable to this population.

A lesbian is a woman whose sexual and affectional orientations are directed towards other women. Her behavior may range from exclusively homosexual, to bisexual, to situationally heterosexual prompted by economic status,

cultural factors, or sexual desire. Not all women who partner with women consider themselves lesbians. The process of choosing to identify with the term is highly individualized and may be fluid over time. The decision may be

influenced by issues of race/ethnicity, socioeconomic class, culture, age, gender presentation, or personal history.

Women who identify themselves as lesbians may do so in their teens, in young adulthood, in middle age, or in 

later life. Lesbians are as diverse as the population at large, crossing all geographic, economic, racial, religious, 

ethnic, age, occupational, and other boundaries.

Lesbians and other women who partner with women have unique health concerns which often go unaddressed

in a medical setting which generally assumes heterosexuality. These specific issues may include cancer screening,

sexually transmitted diseases, human immunodeficiency virus (HIV), depression, substance abuse, relationship

issues, aging, pregnancy, and parenting. Among the most significant health issues for lesbian and bisexual women 

is lack of access to sensitive medical services. Barriers to care may include lack of financial resources or insurance

coverage, past negative experiences with homophobic providers, fear of compromised care related to lesbian identity or behavior, lack of accurate information among both lesbians and clinicians as to the health risks and standards

of care appropriate to the population, and exclusion (or perceived exclusion) from health promotion campaigns. 

In addition, barriers affecting all women such as lack of transportation or child care, language, literacy or cultural

accessibility, fear of painful or embarrassing procedures, fear of test results, and discrimination based on race, socioeconomic class, age, or disability impact lesbians as well. For all of these reasons, lesbians may avoid presenting 

for care until forced to by the severity of their symptoms. This delay in diagnosis and treatment may result in 

poorer health outcomes for the population.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

165

Often articles written about lesbian health issues point to a paucity of research on the population of lesbian

women. Yet in 1994, the National Center for Lesbian Rights published a bibliography of lesbian health research and

articles that included over 800 citations. Many of the articles in that report had been published in peer-reviewed

scientific journals, such as the New England Journal of Medicine, the American Journal of Public Health, the Journal 

of General and Internal Medicine, and the Journal of Nursing Scholarship. Additionally, significant research has been

conducted that has been either published in non-peer reviewed “trade” journals or has not been published at all,

leaving distribution of the analysis of local and regional research projects to informal networks. All of this constitutes a growing body of knowledge about lesbian health.

The difficulties researchers face in studying the lesbian population are numerous and complicate our ability 

to present health status information about this population. Random sampling is complicated when studying a 

marginalized, stigmatized, and fragmented population. Thus, many researchers rely on convenience sampling, 

raising concerns as to the systematic bias in sampling as well as the generalizability of results. Because researchers

face particular difficulty in accessing the most severely marginalized of the lesbian population, study samples tend 

to be comprised of predominately white, middle-class “out” lesbians. Women of color, poor and working class

women, and women who have sex with women but do not self-identify with the term “lesbian” or participate 

in mainstream gay culture remain severely undersampled.

Sampling may be further complicated by the fact that many women, even in anonymous research, do not 

feel safe in disclosing their sexual orientation or the gender of their (current or past) sexual partners. A study 

of self-reported sexual behavior in a sample of women in prison, compared different assessment techniques and

found that same-sex behavior was reported by nearly twice as many women through qualitative assessment 

with a social worker as disclosed via structured questionnaire.

There are extensive data on women in the general population, yet researchers, until very recently, have failed 

to collect or report data on women who have sex with women. These general population surveys include women 

of all sexual orientations but are not analyzed or stratified by the variables of sexual behavior or identity. 

Despite these limitations, the available analysis on lesbian and bisexual women’s health issues is extremely

provocative, indicating critical areas for future research. Points for consideration include:

• The incidence of breast cancer among lesbian women is unknown. There is evidence to suggest some lesbians

may have a higher incidence of nulliparity (bearing no children), oligoparity (bearing few children), and heavy

consumption of alcohol compared with heterosexual women, and may therefore be at increased risk. Existent

research has represented primarily younger, white, well-educated, “out of the closet,” lesbian-identified women,

and is not generalizable to the full diversity of the population. The current data is useful, however, in demonstrating the underutilization of breast self examination (BSE), clinical breast examination (CBE), and screening

mammography among the women surveyed.
Public testimonY

166

• Lesbians appear to be less likely to receive regular Papanicolaou (Pap) smears than heterosexual women.

This is true even among lesbians with a past or current history of heterosexual intercourse, multiple sexual

partners, or sexually transmitted diseases. Often clinicians will consider their lesbian clients to be low risk

based on incorrect assumptions about sexual behavior. In addition, lesbians may be misinformed about

their own risk and the importance of screening.

• Clinical experience suggests that many STDs can be passed between female sexual partners. These include, 

but are not limited to, bacterial vaginosis, trichomoniasis, chlamydia, vaginal candida, herpes simplex

(HSV), human papillomavirus (BPV), the hepatitides, and HIV. Again, insufficient research into woman-towoman sexual transmission leaves us without clear standards of care for treatment of the female partners 

of women with the above listed infections. Prevention guidelines are likewise limited. In addition, the 

stigma and misperception surrounding lesbian sexuality leaves many women without access to accurate

information or a safe venue to discuss sexual concerns with health care providers.

• Lesbians are at risk for contracting HIV through sharing needles for injection of drugs or other substances,

and through unprotected sexual activity with infected male or female partners. Recent research indicates

that among drug-using women, those who reported having any same-sex activity were more likely to engage

in multiple high-risk behaviors including unprotected anal and vaginal intercourse with bisexual or drugusing male partners, sex for money or drugs, sex while high, and sharing injection materials. They were also

significantly more likely to test positive for HIV than drug-using women who reported sex with men only.

• Many lesbian families include children from previous heterosexual relationships of one or both partners,

through adoption, foster parenting, donor insemination, or heterosexual intercourse for the purpose of 

conception. Same-sex relationships have no legal protection and, without documents conferring power 

of attorney, lesbians may be denied the authority to make decisions regarding the care of their partners 

or children, or left without access to or information regarding hospitalized or incapacitated loved ones.

• Although mental illness appears to be no more common among lesbians than among heterosexuals, women

who partner with women do have unique concerns related to their stigmatized status in a homophobic society. Lesbians are often the victims of hate crimes, including verbal or physical abuse or attack, damage to

property, sexual assault or murder. They may be rejected by family, friends, religious community, co-workers

or schoolmates; and they may be denied housing, custody, employment, health care, or legal representation.

Equally devastating are the effects of internalized homophobia, which can lead to low self esteem, isolation,

depression, or self-damaging behaviors. Lesbians affected by domestic violence may not have access to support services sensitive to their needs.

• As with other highly stressed or marginalized populations, lesbians may be at increased risk for the use or

abuse of cigarettes, food, alcohol, and other drugs. While the percentage of lesbians engaging in addictive

patterns of usage has been posited to be greater than that of heterosexual women, research samples may 

not have been representative of the population as a whole. It is more likely that prevalence varies among

sub-populations of lesbians, as it does for other communities. 

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

167

As discussed earlier, the determination of disease prevalence for this population is complicated due to the 

difficulties with research sampling. It is very important, then, to not rely on prevalence alone to determine the

importance of an issue to the lesbian and bisexual women’s community. Diseases or conditions which do not 

appear to be at a higher prevalence for this community, or for which reliable data is not available, can be considered lesbian health issues based on the need for targeted interventions such as lesbian-specific health educational

materials and outreach campaigns. Women who are multiply marginalized as ethnic minorities, as transgendered 

or transsexual, as old or young, or as women without financial access face compounded risks. Culturally competent services, sensitive to the unique needs of lesbians and other women who partner with women, must be

made available to all members of this diverse and underserved population.

Two Decades of Community-based Organizing

Like other communities with poor access to the health care system, the lesbian community has had to build

elements of it’s own health system in order to survive. Throughout the country there are individual service programs for the lesbian, gay, and bisexual communities: youth programs, elder programs, substance abuse and mental

health programs, cancer care and prevention projects, HIV prevention and treatment services, smoking cessation

classes, hotlines, primary care clinics, and community centers. Two cities (San Francisco and New York) have

offices of gay and lesbian health in their local public health departments. Local grassroots projects addressing the

specific health care needs and concerns of lesbian and bisexual women have been springing up across the country

for the last several decades, and are potential sources for researchers to gain technical assistance and access to 

lesbian research subjects, a few examples include:

• Lesbian Resource Project, Phoenix, AZ

• Women’s Cancer Resource Center, Berkeley, CA

• Audre Lorde Lesbian Health Clinic, Los Angeles, CA

• Lesbian Health Project at The Center, San Diego, CA

• Lyon-Martin Women’s Health Services, San Francisco, CA

• Lesbian Health Project, West Hollywood, CA

• Lavender Project, Denver, CO

• Lesbian Health Services at Hartford Gay and Lesbian Health Collective, Hartford, CT

• Lesbian Services Program at Whitman-Walker Clinic, Washington, D.C.

• Mautner Project for Lesbians with Cancer, Washington, D.C.

• GYNA, Miami, FL
Public testimonY

168

• Lesbian Outreach Services at AIDS Atlanta, Atlanta, GA

• Women’s Health Program at Howard Brown Memorial Clinic, Chicago, IL

• Lesbian Community Cancer Project, Chicago, IL

• Emma Goldman Clinic for Women, Iowa City, IA

• Lesbian Services at Chase-Brexton Clinic, Baltimore, MD

• Lesbian Services at Fenway Community Health Center, Boston, MA

• Helping Our Women, Provincetown, MA

• Women’s Community Cancer Project, Somerville, MA

• Women’s Cancer Resource Center, Minneapolis, MN

• New Jersey Women and AIDS Network, New Brunswick, NJ

• Fennimore Initiative for Lesbian Health Care, Pennington, NJ

• Bronx HIV Lesbian Task Force, Bronx, NY

• Shades of Lavender, Brooklyn, NY

• Lesbian Services at Community Health Project, New York, NY

• Lesbian AIDS Project, New York, NY

• Lesbian and Gay Health Project, Durham, NC

• Women’s Services at Nelson-Tebedo Community Clinic, Dallas, TX

• Lesbian Health Initiative, Houston, TX

• Seattle Lesbian Cancer Project, Seattle, WA

National Advocacy Organizing in the 90s

Besides the local and grassroots service agencies, and the national AIDS organizations throughout the country,

other national organizing efforts are taking root to advocate on behalf of the full spectrum of lesbian, gay, bisexual,

and transgender health issues. There are national organizations of lesbian and gay doctors, nurses, social workers,

physicians assistants, addiction professionals, researchers, and gerontologists. Since the early 1990s, there has been

an explosion of national projects addressing the specific health care needs and concerns of lesbian and bisexual

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

169

women. These organizations are potential sources for researchers to gain technical assistance and access to lesbian

research subjects. They include:

• The National Coalition of Feminist and Lesbian Cancer Projects, was formed in 1991, by grassroots 

projects from across the country, to provide national leadership and support the founding and development of other cancer projects.

• The Lesbian Health Fund, a project of the Gay and Lesbian Medical Association, was founded in 1992 

at an annual conference of lesbian physicians and has distributed over $125,000 to fund research and 

education of special interest to lesbians.

• Lesbian health advocates in Washington, D.C. formally established the Lesbian Health Advocacy Network 

in 1993 to share information regarding lesbian health and coordinate activities among individuals and 

organizations interested in the advancement of lesbian health.

• The National Advocacy Coalition on Youth and Sexual Orientation was founded by the Hetrick-Martin

Institute in 1993 to address public policy issues related to lesbian, gay, bisexual and/or transgender youth

through the collaboration of a broad spectrum of national and community-based organizations.

• The National Center for Lesbian Rights began working on lesbian health issues in 1993 with the opening 

of their Policy Project in New York City. NCLR publishes a quarterly Lesbian Health Issues Newsletter which

provides grassroots advocates around the country with resources and information important to their work, 

a Lesbian Health Bibliography with over 800 citations, and other health and legal publications of interest to

lesbians and bisexual women.

• Lesbian Health News, a bimonthly national newsletter, was launched out of Columbus, Ohio, in November

1993. The newsletter works to bring awareness to the lesbian community about women’s well being by

publishing information about health issues, medical conditions, and related problems of interest to lesbians.

• The National Gay and Lesbian Task Force, the National Center for Lesbian Rights, the Human Rights 

Campaign, and the National Gay and Lesbian Health Association were the lead agencies who organized 

the first Lesbian Health Roundtable held in February, 1994. Over 60 lesbian and bisexual women’s health

activists were brought to Washington, D.C. to establish a lesbian health agenda and to attend meetings 

with representatives of the Department of Health and Human Services and members of Congress.

• National Lesbian and Bisexual Women’s HIV Network was formed in 1994, by the Lyon-Martin Women’s

Health Services in San Francisco, to enhance the development of HIV-prevention programs for women 

who have sex with women throughout the United States.

• The National Lesbian and Gay Health Association was formed by a merger between the Association of 

Lesbian and Gay Community Clinics and the National Lesbian and Gay Health Foundation in 1994. 

This merger created the only national lesbian and gay organization focused on health headquartered 

in our nation’s capital.
Public testimonY

170

• The American Association of Physicians for Human Rights, a 15-year-old membership organization of U.S.

and Canadian gay, lesbian, bisexual, and transgender physicians, officially changed it’s name in 1994 to the

Gay and Lesbian Medical Association in order to be more public about gay and lesbian health issues.

• An international Lesbian Research Network was formed in 1996 to assist lesbian researchers from all 

disciplines in gaining access to information, mentoring, technical assistance, and specialized expertise 

on research methodology, funding, and publication.

Inclusion in the Federal Public Health System: 1993-1996

The following list reflects efforts by the U.S. Department of Health and Human Services to include lesbian 

and bisexual women’s health issues in programs, conferences, and written materials since January 1993. This is 

not a complete list of all the ways that lesbians or lesbian health issues have been included but represent those

areas where significant advancements in lesbian access to the federal public health department have occurred. 

One of the most significant advances has been in the open inclusion of lesbian and bisexual women presenting 

at conferences, attending meetings, and participating on advisory committees, thus ensuring the infusion of lesbian and bisexual women’s health concerns throughout the department.

• An historic meeting was held between representatives of national and local lesbian and gay health organizations and Secretary Donna Shalala, prior to the 1993 March on Washington, to begin addressing ways 

the Department of Health and Human Services can better meet the needs of lesbians, gay men, bisexuals,

and transgender individuals.

• The National Institute of Mental Health (NIMH) and the Centers for Disease Control and Prevention (CDC)

cosponsored a workshop in 1993 on suicide and sexual orientation to identify the gaps in scientific knowledge on lesbian, gay, and bisexual youth suicide and make recommendations to researchers.

• The National Institutes of Health (NIH) expanded research on lesbians and bisexual women in 1994 by

providing supplemental funding for NIH-funded researchers to include lesbians and bisexual women in

current studies. In 1994, sexual behavior questions were included in the NIH Women’s Health Initiative 

and sexual identity questions were included in the Harvard Nurses Study after extensive advocacy efforts.

• The Center for Substance Abuse Prevention (CSAP) published the first ever, federally funded “Lesbian, 

Gay and Bisexual Resource Guide” in 1994. This free substance abuse prevention resource guide describes

articles and reports on the topic, lists prevention materials available for this community, and gives resources

for more information.

• In 1994, the U.S. Public Health Service Office on Women’s Health (OWH) included a paragraph about 

lesbian health concerns in a new 4-page publication called Women’s Health Issues.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

171

• All major agencies in the federal Public Health Service met with representatives of the first Lesbian Health

Roundtable in February 1994 to learn more about lesbian and bisexual women’s health issues and to receive

a series of recommendations for their departments.

• The Centers for Disease Control and Prevention (CDC) Breast and Cervical Cancer Early Detection Program

funded a four-city pilot project, beginning in 1995, to develop effective outreach strategies to reach lesbian

and bisexual women for low-cost Pap smears and mammograms.

• An historic meeting of the federal Public Health Service Coordinating Committee on Women’s Health 

was held in January 1995 to address lesbian health issues and concerns.

• The CDC held the first federally sponsored meeting on lesbians and HIV in April 1995 to review the 

available research and knowledge on this topic and to develop recommendations for action.

• The Office of Minority Health (OMH), charged with improving the health status of ethnic minority 

populations, held an historic meeting with lesbian health advocates in 1996 to learn more about the 

health issues affecting lesbian and bisexual women of color.

Health System Recommendations

The D.C.-based Lesbian Health Advocacy Network recommends the following efforts be undertaken within 

the public health system (federal, state, and local) as well as in the private health care field, including hospitals,

medical schools, research institutions, health clinics, and social service organizations to ensure the widest access to

information, services, and research for lesbians, bisexual women, and all women who partner with other women.

Conducting Research

• Include sexual orientation (lesbian, bisexual, heterosexual) and sexual behavior (sex with men, women, 

or both) questions in all research and public health surveillance. Analyze data by the demographic characteristics of sexual orientation and sexual behavior, as well as by age, gender, race, ethnic origin, and

income level.

• Undertake research to better understand those cultural conditions and socialization processes that affect 

lesbian and bisexual women’s health and access to care differently than those of heterosexual women.

• Include lesbian and bisexual women on funding review panels and Internal Review Boards (IRBs). 

Provide sensitivity training for review panels and IRBs to reduce homophobia and increase understanding of lesbian and bisexual women’s health issues.

• Fund researchers, especially lesbian and bisexual women researchers, to include lesbians and 

bisexual women as research subjects and to collect and analyze data stratified by sexual orientation and sexual behavior.
Public testimonY

172

• Undertake research to evaluate the unique conditions that exist for lesbians and bisexual women in 

the causes, prevention, diagnosis, and treatment of cancer, HIV/AIDS, substance abuse, mental health 

disorders, and other chronic diseases.

• Publish recommendations on the methodology of researching lesbians and bisexual women.

Providing Services for the Prevention and Treatment of Disease

• Initiate and augment efforts to increase and expand access to health care for lesbians and bisexual 

women, especially those who are uninsured and underinsured, poor, from rural communities, or 

isolated by virtue of age, disability, or ethnic minority status.

• Include lesbians and bisexual women (as a specific subgroup of women) as a target population in 

all prevention and treatment initiatives for women and adolescent girls.

• Include lesbian health issues and concerns in all women and/or adolescent girls’ health initiatives, 

educational materials, and programs.

• Include lesbian and bisexual health care consumers whenever consumer input is planned.

• Provide sensitivity training for all staff and members of committees or boards to reduce homophobia 

and increase understanding of lesbian and bisexual women’s health issues.

• Include all culturally appropriate methods of treatment in services (including alternative care).

• Fund new and existing lesbian-specific service programs.

Educating and Informing the Public

• Initiate anti-homophobia public health campaigns to reduce the homophobia present in society.

• Develop and fund public health education campaigns targeted to lesbian, bisexual women, and all 

women who partner with other women.

• Include lesbian and bisexual women’s health information and presentations at all conferences and 

meetings where women’s health research, programs, and policy are discussed.

• Publish and distribute lesbian and bisexual women’s health research, educational materials, and 

resource guides.

• Support local and grassroots organizing with an emphasis on developing consumer-based movements.

• Educate members of the media (including lesbian and gay media) to understand lesbian and bisexual

women’s health issues.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

173

Recruiting and Training of Health Care Personnel

• Health care provider and care giver education programs (including continuing education) should promote

sensitive, culturally competent, language-appropriate patient care for lesbian and bisexual women.

• Medical, nursing, and other health professional schools should incorporate training regarding lesbian 

and bisexual women’s health and the provision of sensitive and culturally competent care as essential 

portions of the curricula.

• Ensure freedom of choice of medical providers in any health insurance plan (including managed care 

plans) or health system.

• Recruit and support lesbians, bisexual women, and lesbian-sensitive individuals as applicants to medical,

nursing, and other health professional schools.

Designing Guidance on Lesbian and Bisexual Women’s Health Initiatives

• Encourage health institutions to appoint a lesbian/bisexual health liaison to assist in the development 

of services to improve the health condition of lesbians and bisexual women.

• Encourage the formation of lesbian, gay, and bisexual employee groups to assist in the planning of services

and research for the lesbian and bisexual women’s communities.

• Encourage the development of consumer-based lesbian and bisexual women’s health advisory committees.

• Develop a lesbian and bisexual women’s health agenda to provide guidance for future health initiatives.

The Lesbian Health Overview section has been adapted with permission from: “Women’s Health Issues: Planning 

for Diversity” by E.J. Rankow, 1995.

Linda Quander, Ph.D. Clark Atlanta University

Strategic management is a process which requires planners and decisionmakers to accomplish key tasks:

• Clarify purpose;

• Select goals and objectives;

• Identify present strengths and weaknesses;

• Analyze future opportunities and threats;
Public testimonY

174

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

• Compare strengths and weaknesses to opportunities and threats;

• Decide on long-term strategy;

• Implement the strategy; and

• Evaluate the strategy.

Women’s health researchers must learn to anticipate rapid changes that affect their projects, working groups,

organizations, and even their careers. Conferences — such as this one — can facilitate this by basing training, 

education, and development on projected future needs.

Needs assessment is critical for identifying learning gaps and discovering weaknesses. It is part of the process

in which we ascertain future needs relative to overall performance in women’s health care. Therefore, effective communication about needs assessment is paramount in designing, implementing, and interpreting research programs.

Researchers must be aware of how communication can ultimately enhance or adversely affect women’s health.

NIH and the National Institute of Environmental Health Sciences are to be commended for recognizing that

scientific knowledge, combined with effective communications, can empower women to better control their personal environments and thus improve their overall health. I am particularly enthusiastic about NIH’s Women’s

Health Initiative, an important study of strategies that can enhance adoption of healthy behaviors by using a 

multidisciplinary approach in cooperation with various community-based prevention centers.

Researchers need to analyze various types of traditional and nontraditional channels. For example, studies 

of African-American women have found that churches are a particularly useful route. We now know that it is

important to understand how and why community-based prevention centers appear to be effective in reaching

minority populations.

Communication channels to women must be future oriented and proactive. Strategies need to see women 

as active, adaptive team members, not as passive obstacles to progress. Cooperative partnerships are effective 

tools for addressing inequality in health care for women and reaching women throughout the community.

James M. Roberts, M.D. Society for Gynecological Investigation

One of the refreshing aspects of the increased emphasis on women’s health research attributable to the

Women’s Health Initiative is the heightened awareness that women’s health is not limited to reproductive health.

Research has shown that there are gender differences in many aspects of health and medicine, and recognition of 

this phenomenon has led to changes in how women are treated for illnesses not directly related to their gender.
Public testimonY

VOLUME 4

175

Indeed, we are now seeing improvements in female morbidity and mortality statistics that reflect this revision 

in medical approaches and attitudes toward female patients.

It is now generally recognized that many diseases manifest themselves differently in women than in men.

Women face different cardiovascular risks than men, which has certain implications for diagnosis. Similarly, 

women appear to be more susceptible than men to illnesses such as autoimmune disease, and we now know 

that women metabolize drugs differently than men.

Of course, we should not abandon research on reproduction health. Reproductive health statistics such 

as premature births remain alarmingly high, particularly in disadvantaged populations. Likewise, death from

preeclampsia — a condition recognized for more than 1,000 years — is the highest cause of maternal death 

in developed countries. Death rates also remain high for infants of preeclamptic women.

Research in these areas has led to many exciting discoveries with important treatment possibilities for 

genetic ailments. New findings in molecular biology, and our ability to handle data more effectively, provide 

us with opportunities to solve major problems that have affected women and infants.

We must also ensure that researchers interested in women’s health are nurtured and supported throughout

their academic and professional careers. Money for training — both federal and private — is extremely important.

Still, our most valuable resource is the cadre of talented individuals embarking on scientific careers, including 

the generation of future scientists now in grade school. 

In this time of restricted resources and academic upheaval, we must resist the urge to complain that things 

are worse than ever. We must “hang tough” and remember the importance of our goal. We must convey to our

young successors the rewards, excitement, and vital importance of research relevant to women’s health.

Association of Black Cardiologists

Roxanne A. Rodney, M.D. Committee on Cardiovascular Diseases in African-American Women

(Testimony prepared by the Association’s Committee on Cardiovascular Diseases in African-American

Women: Sheila A. Robinson, M.D.; Roxanne A. Rodney, M.D.; Hannah A. Valantine. M.D.; and Jan 

D. Webber, M.D.) 

Cardiovascular Diseases in African-American Women

The Association of Black Cardiologists is committed to the prevention, diagnosis, and treatment of 

cardiovascular diseases in African-American women.
Public testimonY

176

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Cardiovascular diseases are diseases of the heart and blood vessels which include: coronary heart disease 

(heart attack), stroke, and hypertension (high blood pressure). Cardiovascular disease affects 1 in 5 women, 

and is the major cause of death in women. In fact, more than 479,000 women die annually of cardiovascular 

disease, surpassing the 444,000 men annually who succumb to cardiovascular death. In women, cardiovascular

deaths are almost double the 246,000 deaths attributed to all cancers. Indeed, five times as many females die 

from heart attack than from breast cancer.

African-American women are at greater risk; they have a higher prevalence of and a higher mortality rate 

due to cardiovascular disease compared with Caucasian women. The cardiovascular death rate in 1992 in 

African-American women was 69.2 percent higher than that in Caucasian women.1,2

Coronary Heart Disease, Hypertension, and Stroke

Coronary heart disease is the number one killer of American women. Approximately one half of all deaths, 

or one-quarter million deaths due to heart attack, occur in women. African-American women are disproportionately affected. In 1992, the death rate from coronary heart disease was 32.6 percent higher in African-American

women than in Caucasian women. Between ages 35 to 74, the death rate from heart attack in black women is 

twice that in white women and three times that in women of other races.

It has been reported that black women had the highest mortality rate after heart attack at 48 percent compared

with white women (32 percent), black men (23 percent), and white men (21 percent). The survival rate in AfricanAmerican women is 69 percent lower than that in Caucasian women after an out-of-hospital cardiac arrest.

Approximately one-half million Americans per year sustain a new or recurrent stroke, according to Framingham Heart Study data. African-American women have the highest estimated crude prevalence of stroke at 2.5 percent (compared with 1.9 percent in white women, 2.2 percent in white men, 1.8 percent in black men, and 0.8

and 1.1 percent in Mexican-American women and men, respectively).3 Women have a higher stroke death rate 

at 61 percent compared with men at 39 percent. In addition, the mortality rate in black women is 77 percent 

higher than that in white women.

Hypertension afflicts an estimated 43 million American adults. African Americans have a 40 percent higher

age-adjusted prevalence of hypertension than that in Caucasians and Mexican Americans. The onset of hypertension is earlier, and it is more severe in blacks, resulting in a 1.8-fold greater rate of fatal stroke, a 1.5-fold greater

rate of heart disease deaths, and a fivefold greater rate of end-stage kidney disease compared with whites.

Between the ages of 30 to 69, the prevalence of hypertension is greater, and the mean systolic and diastolic

blood pressures are higher in African-American women than that in Caucasians and Mexican-American women. 

In the 60 to 69 age group, 80 percent of African-American women versus 55 percent of Caucasians and 60 percent 

of Mexican-American women have hypertension. The mortality rate due to hypertension is higher in women 

compared with men, 58 percent versus 42 percent, respectively.
Public testimonY

VOLUME 4

177

Risk Factors

Hypercholesterolemia. Fifty-one percent of African-American women aged 20 and above have undesirably

high serum cholesterol levels of greater than 200 mg/dl; 19 percent have levels above 240 mg/dl. In black females

age 19 and under, hypercholesterolemia, defined as > 170 mg/dl in this age group, is present in an estimated 

46 percent of this group, compared with 32 percent in white females.

Lp(a) lipoprotein levels, which correlate directly with an increased, independent risk for coronary heart 

disease, are twofold higher in black than in white women.4–7

Diabetes. Eight percent of black women have diabetes, compared with and average of 3 percent for all 

other women. The risk of an initial heart attack is more than doubled in women with diabetes, and in contradistinction to men, diabetes contributes significant increased risk for subsequent heart attack in women.

Smoking. Twenty percent of African-American women over age 18 are smokers. Smoking and the concurrent 

use of oral contraceptives significantly increase the risk of stroke.

Physical Inactivity/Overweight. Lower socioeconomic and educational levels tend to correlate with a higher

likelihood of a sedentary lifestyle. Physical inactivity is associated with an increased relative risk of coronary heart

disease, which ranges form 1.5 to 2.4. This increased risk is comparable to that attributed to hypertension, hypercholesterolemia, and smoking. Physical inactivity contributes a 30 to 50 percent increased risk of hypertension.

Approximately 68 percent of African-American and 56 percent of Caucasian women do not engage in regular 

physical activity.

Fifty percent of African-American and 32 percent of Caucasian women are 20 percent or more above desirable

weight. More than 30 percent overweight is an independent risk factor for cardiovascular diseases.

Recommendations

Cardiovascular disease is the major cause of mortality in women. The number of deaths sustained by women

due to cardiovascular diseases exceeds that in men. African-American women have a higher prevalence of, and 

a higher mortality rate due to, cardiovascular disease compared with Caucasian women.

The Association of Black Cardiologists unequivocally supports increased funding of clinical and basic science

research in cardiovascular diseases in African-American women. Women in general, and African-American women 

in particular, have been underrepresented populations in research studies. Historically, the assumption has been

that data collected in men would be applicable to women. Time has revealed this fallacy. Nor can it be assumed

that data generated in studies of white women are translatable to black women, given the differences in risk factor

prevalence and severity. In order to obtain accurate data on at risk populations, these groups must be included in

research studies. It is cost effective to increase the fund of medical knowledge regarding disease processes in at-risk

groups through targeted research, for this engenders appropriate interventional strategies in the modification of 

etiologic factors and in the treatment of disease processes.
Public testimonY

178

The second critical component of this strategy to reduce cardiovascular morbidity and mortality in AfricanAmerican women involves educational programs for at-risk populations specifically targeting primary disease 

prevention through risk factor modification, and emphasizing the importance of seeking early appropriate care 

if symptoms are present in order to reduce the incidence of secondary complications. Coupled with this, health

care providers must also continue to be educated in the prevention, timely diagnosis, and appropriate treatment 

of cardiovascular diseases in African-American women.

In addition to the immeasurable impact of cardiovascular morbidity and mortality on the lives of AfricanAmerican women and their families, the societal impact, in terms of lost productivity and health care expenditure,

can not be understated. Health care dollars are more effectively utilized by the generation of accurate research data,

which can then be appropriately implemented via the education of at-risk groups and health care providers. This

strategy is medically appropriate and cost effective.

References

1 Heart and Stroke Facts: 1996 Statistical Supplement, American Heart Association.

2 National Health and Nutrition Examination Survey II, 1976-1980.

3 Burt V, Whelton P, Roccella EJ, et al. Prevalence of hypertension in the U.S. adult population. Results from the Third 

National Health and Nutrition Examination Survey, 1988-1991. Hypertension 1995; 25:305–313.

4 Heiss G, Tamir I, Davis CE, Tyroler HA, et al. Lipoprotein-cholesterol distributions in selected North American Populations: the Lipid Research Clinics Program Prevention Study. Circulation 1980; 61:302–315.

5 Fulwood R, Rifkin B, Russell-Briefel R, Muesing R, LaRosa J, et al. Trends in serum cholesterol levels among United States

adults ages 20-74 years, from National Health and Nutrition Examination Surveys, 1960-1980. JAMA. 1987; 257:937–42.

6 Morrisett JD, Gugto JR, Gaubatz JW, and Gotto AM, Jr. Lipoprotein [a]: structure, metabolism and epidemiology. In: Gotto

AM Jr (ed.). Plasma Lipoproteins. New York: Elsevier Science Publishers BV; 1987: 129–52.

7 Uterman G. Lipoprotein(a): a unique risk factor for atherothrombotic disease. Arteriosclerosis 1990; 10:672–79.

Department of Health Education

Sheryl Burt Ruzek, Ph.D., M.P.H. Temple University

Research Agendas Focusing on Diverse Pathways to Health

I will suggest that we need to refocus our national research agenda to address: (1) the prerequisites to women’s

health that are ignored in a narrow biomedical paradigm; (2) pressing issues in social and behavioral paradigms;

and (3) ignored or suppressed research questions grounded in mind/body, alternative, and folk healing traditions.1

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

179

Why We Must Move Beyond Narrow Biomedical Models

My testimony today reflects disquietude with the definition of women’s health that is widely used in 

government and medicine.2

Women’s health is devoted to the preservation of wellness and prevention of illness in women, and includes

screening, diagnosis, and management of conditions which are unique to women, are more common in women, are

more serious in women, [and] have manifestations, risk factors, or interventions which are different in women

(1991:149 emphasis added).

This definition obscures critical dimensions of women’s health and must be revised. Emphasizing the preservation of wellness implies that women have wellness to preserve, leaves where health comes from undefined, 

and glosses over the fact that some women do not have access to the basic life conditions that produce health.

Retaining such a narrowly biomedical definition that focuses on diseases or “conditions” in women, institutionalizes individual expectations and collective demands for biomedical interventions at a time when access 

to medical care is particularly problematic. We need to more carefully weigh what research is needed to make 

the greatest improvements in the health status of women who are particularly disadvantaged in terms of health 

status. We need to question the wisdom of adopting a research agenda that may break new scientific ground, 

but widen the gap between the health of different groups of women.

Embracing the WHO Vision of Health

As we move toward global thinking, we may do well to adopt research priorities that reflect the vision of 

health that the World Health Organization (WHO) promotes as “a state of complete physical, mental, and social 

well being and not merely the absence of disease or infirmity.” This often cited definition is very different from 

the Public Health Service definition in the attention given to medical services relative to well being. The WHO

includes in its definition of health a number of “prerequisites for health:” freedom from the fear of war; equal

opportunity for all; satisfaction of basic needs for food, basic education, water and sanitation; decent housing;

secure work and a useful role in society; and political will and public support.3

The WHO prerequisites for health have important gender dimensions and raise critical issues about social class

and culture in the production of health. For example, the threat of war reduces women’s health not only directly

through the threat of death, rape, or destruction of working and living conditions, but indirectly through emotional

stress related to the survival and safety of communities and family members and the disruption of education. Does

the “war on drugs” in inner cities have such an impact on women’s health? Can we address how our social policies

provide equal opportunity for women of all races, social classes, and with other particular social characteristics, to

attain health? Should our research agenda on women’s health include research on how the quality of housing, education, food, heating, water, and other necessities of life affect women’s physical, mental, and spiritual well being?
Public testimonY

180

In communities, women not only need to be free from the fear of war, but from all forms of violence. American

society must come to terms with this prerequisite to health or all of the breast cancers “caught early,” the chronic

diseases avoided through positive health practices, and the benefits of new technologies will be undermined and

overshadowed. The specter of women being screened annually for a multitude of diseases but remaining fearful of

leaving their homes — or perhaps worse yet, fearing remaining in them — raises uncomfortable questions about

how narrowly women’s health is often defined. I hope that ORWH will take a leadership role in defining “what’s

important” for producing health by crafting a national research agenda that will address how to promote and preserve the health needs of women who are malnourished, homeless, or living under stressful social, psychological,

and economic conditions. The complexities and differences in women’s health by race, by social class, and by 

culture raise critical questions about how to assign priorities for research that will promote equity, not widen 

the gap between women in different social groups. May we be mindful of this larger social need as we develop 

our national research priorities.

Finding a Proxy Measure for Social Class

Since we resist measuring social class, a women’s health research agenda might profitably build on National 

Center for Health Statistics (1995:108) reports of a clear gradient in mortality both for white women and women 

of all races by educational attainment. In 1992, the death rate was twice as high as for white women and women 

of all races aged 25 to 64 who had less than 12, compared to 13 or more years of education. If research on 

women’s health included educational attainment, the importance of education for women’s health would be more

widely recognized. Including education as a variable in research would also help interpret findings that are reported 

by race or ethic group. Many socioeconomic factors are obscured when research is reported only by race, promulgating distorted views of relationships between race, per se, and health. More attention needs to be paid to

health status differences among women within racial/ethnic groups. Such research provides clues to differences

between sociocultural and socioeconomic factors that affect health status and thereby suggest different strategies 

for improving women’s health. For example, some immigrants have better health and birth outcomes than nativeborn members of the same racial/ethnic group despite similar poverty levels (see, e.g., Kumanyika and Golden,

1991; Scribner and Dwyer, 1989). Such findings should spur research on the contributions of culture and 

acculturation as determinants of women’s health.

Recognizing Alternative Models of Health

Emerging mind/body models that emphasize psychological and spiritual dimensions of health seem particularly

invisible in federal agendas for women’s health. These models start with the assumption that the mind and body

interact in complex ways and challenge separating mental/emotional states from physical symptoms. We clearly

need more research on how women’s health needs are addressed in traditional non-western healing systems that

posit spiritual as well as psychological dimensions of health. Christiane Northrup, former President of the American

Holistic Medical Association (1994), cogently argues that surgery, drugs, and even good nutrition and health practices are not enough to promote healing. The emotional matters that brought about the physical symptoms must 

be resolved for real healing to occur. Surely these increasingly popular ideas are worthy of research attention. 

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

181

When women’s health problems are simply portrayed as “all in the head,” physicians view them as unworthy of

either scientific investigation or clinical attention. The stigma associated with psychogenic disorders contributes

substantially to women’s dissatisfaction with conventional medical treatment. If new research in psychoneuroimmunology and other areas scientifically demonstrate how what happens psychologically and emotionally 

“gets into the physical body,” mind-body concepts may truly benefit women.

Important relational concepts, such as caring, deserve more recognition. Few research resources are available 

for studying how caring facilitates health and healing. The subjective, experiential dimensions of health and healing, addressed in the qualitative social sciences and in some areas in nursing, as well as in mind-body paradigms,

deserve greater attention. So do alternative healing practices and the contributions of a much wider array of 

healers and helpers than are generally acknowledged under the rubric of “health care workers.”

Looking for Integrative Concepts and Theories

Theoretical and conceptual work is needed to link empirical research areas to one another. Integrated models 

are needed to understand how working and living conditions, individual health behaviors, psychological and 

emotional processes, and effective biomedical interventions together contribute to health and well being. We 

can ill-afford to promote a research agenda that locates women’s health only in the domain of biomedicine, 

ignoring the social forces that create — and undermine — health. New integrative concepts are sorely needed.

Women’s health research must also explicitly take into account the health of men, children, parents, and 

life partners. Extending the analysis of health to include significant others in women’s lives underscores the 

critical importance of gender in the production and maintenance of women’s health. Women from all walks 

of life emphasize the need to be free from the fear of violence, in all its many sociocultural forms — including 

violence among and between men who are women’s kin. Addressing violence against women outside the context of male as well as female gender expectations and opportunities is unimaginable. For women, a stable 

economic base of jobs is essential for maintaining the prerequisites for health as well as gaining access to 

medical services. Theories and concepts that lay out how to create and maintain social relationships and 

institutions that actually produce health are sorely needed.

Some Specific Research Questions for the 21st Century

In a broader framework for understanding women’s health, there are many questions that deserve attention; 

I shall only sketch out a few here.

• Culturally appropriate services. Will more culturally relevant and effective care emerge from ethnically distinct 

service providers than “mainstream” institutions or dominant group providers, and if so, what provisions 

can be made to foster the continued existence of community-based services that are targeted to specific

racial/ethnic groups? Do some forms of ethnically/culturally targeted services offer advantages that benefit

women? What are the opportunities for fostering culturally appropriate services for other groups? Can 

such models of care, developed by and for specific populations, be “mainstreamed” successfully?
Public testimonY

182

• Health statistics within and between specific racial/ethnic groups and socioeconomic groups reveal widely divergent 

patterns of health and ill health. These descriptive data should raise new research questions about links between

race/ethnicity, socioeconomic status, the cultural context of health practices, and the availability of health 

services (Krieger, et al. 1993). The very favorable health status of most groups of Asian-American women

should raise questions about how some groups generate such good health.

• Qualitative research issues. Women’s experiences of health and illness needs greater attention to understand 

how women in different life situations view and make decisions about health, disease, and health-related 

issues on their own terms, drawing out culturally and psychologically relevant concepts. Related to this is

investigation of women’s own definitions of their health care needs and goals — that may differ from those 

that “experts” perceive as priorities. Research must also address what women perceive as poor, bad, demeaning, or coercive health actions. Narrative accounts and case studies provide distinctive insights into the actual

conditions of women’s lives that may offer clues for more effective preventive or treatment efforts. Other

research questions address how women perceive that they are actually treated when medical technicians

process them through mammography screening, draw blood for laboratory tests, or carry out diagnostic 

procedures. How is the experience different for women with disabilities? for women who do not speak the 

language of providers? for women whose cultural background differs? What is the actual experience of being 

an experimental subject to test a new drug or treatment? How does social class (approximated by education)

shape this and other health care experiences?

• Alternative health. More research on alternative practitioners used by women in all ethnic groups, in both 

rural and urban settings, would alter dominant views of what constitutes “the” American health care system.

Serious study of utilization of traditional healers, as well as other less conventional therapies, would tell us

how women protect and improve their health. Given the documented use of alternative therapies and the 

anecdotal evidence about its popularity, research might profitably compare how patients are treated in such 

settings compared to mainstream medical institutions (Moore and Milligan 1994; O’Connor 1995). There 

is considerable anecdotal evidence suggesting that alternative practitioners often interact with patients in 

ways that are experienced as supportive and healing — and rarely found in impersonal conventional medical institutions. Is some of the appeal of midwives their interpersonal skills and their ability to respect the

diversity of women’s desires for positive birthing experiences?

In mental health, where the cultural fit between patients and practitioners may be especially important, 

case studies of traditional healers may reveal conceptualizations of mental health and illness that are much 

more congruent with peoples’ lived experience than the diagnostic categories currently used. For women 

of color and ethnic women, the constructs of psychotherapy need to be enlarged and revised to address 

ethnic and cultural issues that bridge the gap between the usually white middle-class world of professional 

therapists and their clients.

• Epidemiologists must study social and environmental, as well as biological and behavioral, risk factors in diverse 

groups. Socioeconomic status and race simply can not be treated as “control” variables but must be reconstructed as important independent causes of poor health status. Patricia O’Campo and her colleagues (1995)

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

183

have proposed a promising contextual analytic approach that represents one promising direction to pursue. 

In short, a broader range of conditions than the “leading causes of death” also need to be studied in an epidemiological framework to counterbalance the dominant view that the so-called “killer diseases,” such as 

cancer and heart disease, are more “important” to control than the living and working conditions that 

reduce well being over the entire life cycle.

• Determining what is “important” to study. A specific example is research on violence which includes the social

and psychological effects of violence and perceptions of risk of violence, not just homicide rates. While it is

often argued that homicide is the “tip of the iceberg,” women should ask why the whole iceberg is not being

mapped given the resources being spent on mapping the human genome. While genetic information may lead 

to improved health, changing social, psychological, and environmental conditions would surely have large 

pay-offs in terms of women’s health and well being. And, as O’Campo and her colleagues (1995) point out, 

a clearer understanding of which elements of social environments are most predictive of violence against

women could lead to better targeting of resources.

Summation

In sum, health is multifaceted and our national research agendas must include what women want and need to

realize the vision of health set forth by WHO. Our research agendas must broaden to incorporate psychological and

spiritual dimensions of health and healing that have particular significance to women who see these as contributing

to their ability to resist and recover from ill health. Attention to the broader base of what actually produces health

(as contrasted to managing or screening for disease) suggests that investments in a variety of areas are necessary to

promote women’s health. Women from diverse backgrounds must be involved in setting national research priorities

to ensure that we address the prerequisites to health and disease states.

References

1 These issues are discussed at length in S. Ruzek, V. Olesen, and A. Clarke (Eds.). Women’s Health: Complexities and Differences. Columbus: Ohio State University Press, in press 1996.

2 For example, this definition was adopted September 26, 1994, by the National Academy for Women’s Health Medical Education (NAWHME), a joint program of the Medical College of Pennsylvania and the American Medical Women’s Association.

3 These are described in detail and analyzed by Downie, Fyfe, and Tannahill (1990:62).

Other Resources

Krieger, N., D. Rowley, A. Herman, B. Avery, and M. Phillips. “Racism, Sexism and Social Class: Implications for Studies 

of Health Disease and Well-Being.” American Journal of Preventive Medicine (96 Supplement):82–122, 1993.

Kumanyika, Shiriki K. and Patricia M. Golden. “Cross-sectional differences in health status in U.S. racial/ethnic minority 

groups: Potential influence of temporal changes, disease, and life-style transitions.” Ethnicity and Disease 1:50–59, 1991.

Moore, Ellen Singer and Maureen Mulligan (Eds.). The Empathic Practitioner: Empathy, Gender and Medicine. New Brunswick, 

NJ: Rutgers University Press, 1994.

National Center for Health Statistics. Health, United States, 1994. Hyattsville, Maryland: Public Health Service, 1995.

Northrup, Christiane. Women’s Bodies, Women’s Wisdom: Creating Physical and Emotional Health and Healing. New York: 

Bantam Books, 1994.
Public testimonY

184

O’Campo, Patricia et al. “Violence by male partners against women during the childbearing years: a contextual analysis.” 

American Journal of Public Health 85:1092–1097, 1995.

O’Connor, Bonnie Blair. Healing Traditions. Alternative Medicine and the Health Professions. Philadelphia: University of 

Pennsylvania Press, 1995.

Scribner, R. and J.H. Dwyer. “Acculturation and low birthweight among Latinos in the Hispanic HANES,” American 

Journal of Public Health 79:1263–1267, 1989.

Eleanor G. Shore, M.D., M.P.H. Harvard Medical School

The representation of women at Harvard Medical School (HMS) and Harvard School of Dental Medicine

(HSDM) in 1996 range from a high of 49 percent for students to a low of 7 percent for the rank of Professor. At 

the student, trainee (clinical or research fellow), and instructor levels, representation is consistent with or better

than the availability pool; however, at the voting faculty ranks (Assistant Professor and higher), the percentages

reflect a critical problem. Even among those women already appointed as Instructors or Assistant Professors, 

a smaller percentage are promoted over a 10-year period than their male colleagues.

The Office for Faculty Affairs has launched a number of interventions to try to correct this gender gap including the establishment of appointment procedures designed to assure that new faculty positions are accessible to 

all qualified candidates; the requirement for formal annual career conferences for women and underrepresented

minorities to assist in career planning and direction; and career assistance by conferences, workshops, and ad hoc

individual counseling for trainees and junior faculty through the Office for Academic Careers, Minority Faculty

Development Program, Women in Academic Medicine Program, and the Office for Faculty Affairs.

The most serious problem faced by women in their academic careers is demonstrating independent academic productivity (research, teaching, grant application, and paper writing) because of a lack of sufficient 

protected time for these activities. Without substantial tangible evidence of academic creativity, promotion 

comes more slowly, if at all. The 50th Anniversary Program for Scholars in Medicine provides for ten fellowships a year for women or men who can demonstrate both great academic promise and complicating personal

responsibilities which might be remedied by a grant of $25,000. In the first competition, more than 210 

women and men applied for the ten fellowships.

A similar set of national fellowships could make a large difference in diminishing the gender gap. Given the

challenges in the biomedical field for the 21st century, and the fact that more than half of the students in science

and medicine at HMS are women, there is every incentive to support these women through the hardest time in

their professional lives. Men qualify for the great majority of sabbaticals at HMS since they occupy 93 percent 

of the senior positions that are covered by the University’s sabbatical policy. It seems only fair that institutional

resources be directed at an earlier point in women’s careers when the need is greatest, rather than saving the 

support for a sabbatical that few women will ever reach without this additional help earlier in their careers. 

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

185

Martha Torres-Montoya, M.S.P.H. Hispanic Women’s Health Association

Research into the health needs of Hispanic/Latina women is very limited at present. Notably meager are epidemiological data, program evaluation models, effective interventions, and clinical trials. Where such research

exists, it generally focuses on issues of access — health insurance, geographic, language, and cultural barriers.

As a result, little is known about Hispanic/Latina women’s health issues and status. The inability to describe 

the problems or document the needs has put these communities in a poor position to obtain government funding.

This lack of original research has seriously impeded health service agencies and community-based organizations

from addressing gaps in health care for Hispanic/Latina women. Until and unless community-based agencies are

able to document health and social problems affecting Hispanic/Latina women, federal funds are unlikely to be

forthcoming. The result is poor, ineffective health care policies that, in turn, impact the availability, distribution,

and utilization of scarce health care dollars.

The Hispanic Women’s Health Association (HWHA) has a strong commitment to developing and implementing successful research projects in the Hispanic community. We recommend that ORWH conduct research into 

the following areas of importance to Hispanic/Latina women:

• Differences in health perceptions, physical and mental health, and social support systems;

• Impact of welfare reform;

• Impact of acculturation on health status;

• Health beliefs and practices;

• Preconceptional health issues for use in a national campaign;

• Infertility;

• Depression, cultural perceptions, and coping strategies;

• Interventions to reduce teen pregnancy;

• Interventions that encourage men to become involved in family planning;

• Alcohol use/non-use; and

• Patterns of family formation.

HWHA also urges ORWH to revisit the recommendations made for Hispanic/Latina women in 1991. It

requests that ORWH prepare a report that describes how those recommendations were implemented in the 

past 5 years and/or how they could be integrated into the 1996 agenda.
Public testimonY

186

Laura L. Tosi, M.D. American Academy of Orthopaedic Surgeons

Women are far more prone than men to hip fractures and bone-related diseases such as osteoporosis, and 

their susceptibility increases with age. The associated loss of life and suffering involved in fracture and disease 

is enormous, as are the medical bills, which approach $10 billion each year.

As a mender of broken bones, the American Academy of Orthopaedic Surgeons (AAOS) is deeply concerned

that nearly 300,000 individuals will suffer hip fractures this year and that women’s fractures will outnumber men’s 

by almost three to one. In addition, women over age 65 have a one in five chance of suffering a hip fracture during

their lifetimes.

These statistics demonstrate the importance of early intervention in reducing the prevalence of osteoporosis.

Since many orthopaedic injuries are preventable, early intervention provides the greatest potential for reducing the

numbers. As such, education and intervention must begin in childhood. Although evidence shows that increasing

calcium intake during adolescence is critical in the development of peak bone mass and growth, there is a desperate need for longer, prospective trials. We need data confirming the current actual intake of calcium in our young

people. We also need to determine how we can encourage young people to alter their dietary lifestyles.

While the Academy is concerned with osteoporosis and resultant injuries, we are also interested in the incidence of sports injuries in young female athletes. Athletes and their coaches need to be instructed more effectively

about the orthopaedic risks associated with playing sports. Investigation into the increased risk of knee injury in

young female athletes, as opposed to young male athletes, in also essential. Strengthening strategies and training

techniques must be explored at every level so that injuries can be prevented.

For many years, AAOS has devoted tremendous energy to osteoporosis research and injury prevention; a campaign called LIVE IT SAFE, which we sponsored with the American Association of Retired Persons, is one example.

Although we believe these programs are effective, our own goals are to expand these efforts so that we can better

understand the needs of young women and design effective educational strategies to improve their health habits.

The Academy commends the Office of Research on Women’s Health (ORWH) for its extensive work in encouraging research on solutions to women’s health problems, such as osteoporosis. We believe ORWH can and should

play a leadership role in identifying the key cause-and-effect relationships of osteoporosis. The cost of education,

intervention, prevention, and rehabilitation amounts to several billion dollars a year. Nevertheless, the improved

quality of life is incalculable.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Public testimonY

VOLUME 4

187

Gastroenterology Women’s Coalition

(Representing the American Gastroenterological Association,

American Society for Gastrointestinal Endoscopy, 

American Association for the Study of Liver Diseases, 

Jacqueline Lee Wolf, M.D. and American College of Gastroenterology)

Colorectal cancer is the second deadliest cancer in the United States and the third leading cause of cancerrelated death in women. Women with hereditary colon cancer are at increased risk of ovarian and endometrial 

cancers. Further study of colon cancer in women may provide important information on the etiology of these 

associated cancers. Also, further research is needed on how gender and knowledge of genetic status affect 

screening participation.

Basic and clinical research is needed on the pathogenesis, immunology, and therapeutic approach to primary 

biliary cirrhosis, a disease nine times more common in women than in men. Among the additional aspects of 

liver disease in women that merit expanded study are: the impact of sex hormones on elements of the immune 

system and on the proliferation of liver cells; the factors responsible for differences between men and women 

in alcohol absorption and metabolism; and the effects of estrogen and progesterone on the development of 

alcoholic liver disease.

The Helicobacter pylori bacterium is a relatively new discovery that has revolutionized and advanced treatment

for peptic ulcer disease. Studies show that H. pylori-infected women are 15 to 18 times more likely to develop 

gastric cancer than infected men. Further research is needed on the role of acid secretion in protecting against the

development of gastric cancer and on clinical approaches to preventing gastric cancer. Research on the prevention

of peptic ulcer disease induced by non-steroidal anti-inflammatory drugs (e.g., aspirin and ibuprofen) is needed.

Gallbladder and biliary tract disease are twice as common in women as men. The role of estrogens and progesterones in the formation of gallstones, particularly during and immediately following pregnancy; the basic 

biology of gallstone formation; and potential preventive measures merit further study.

Irritable bowel syndrome and functional bowel disorders are twice as common in women as men. Additional

research is needed on the effect of the menstrual cycle on functional bowel disorders; and the relative impact of

genetics, the environment, and social factors on the etiology and perpetuation of symptoms.

Aside from research priority objectives, the Coalition recommends the following mechanisms for enhancing

biomedical research career opportunities for women: NIH should expand small grant support for mentoring programs for women; NIH should provide seed money for the initiation of special academic tracks for women interested

in research careers; academic institutions should be encouraged to adopt “stop the clock” policies with regard 

to tenure and promotion of women faculty; NIH should allow institutions to include in their indirect cost calculations, programs to prepare women faculty members for senior administrative positions (departmental chairs or

deans) through which they can continue to foster research and influence the research activities of their institutions. 
188

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Public testimonY

Elizabeth Yoffe, M.A. Self

Conventional medicine is a wonderful, lifesaving, and life-enhancing tool. However, its long monopoly in 

the overall health care picture is beginning to loosen as lay people, insurance companies, and even parts of the

medical establishment recognize that alternative therapies can complement conventional medicine.

My interest in the health care system was sparked after I suffered a crippling stroke at the age of 30. Conventional medicine and rehabilitative therapy literally got me back on my feet, but their value in the recovery

process was limited. To improve my physical functioning, I turned to alternative healing methods: meditation,

relaxation techniques, and visualization. I became more intrigued by what was then called “unconventional 

medicine” and set out to learn more about alternative modalities.

Today, more people — especially women like me — are questioning the existing medical system, taking 

control and responsibility for their health, and exploring alternative treatments for chronic or degenerative 

illnesses. However, resistance to alternative healing persists, particularly from conventional practitioners.

There are interesting links between the emerging fields of women’s health and alternative medicine. Both 

are regarded as outside the medical norm. The same can be said about medical practices that originate in China

and India, which are far older and more refined than Western medicine. There seems to be an assumption that 

only medicine developed from a Western cultural perspective is “real.” Other medical traditions are regarded 

as backward or primitive. Alternative medicine may receive more acceptance from women patients and health 

practitioners because, historically, women have a deep bond with natural or folk remedies.

It is ridiculous to deny people education about, and access to, alternative therapies that might help them

recover or better manage illness. I recommend the following steps:

• Increase cooperation between the Office of Research on Women’s Health and the new Office of 

Alternative Medicine (OAM);

• Integrate findings from OAM into public health education programs;

• Integrate alternative medical modalities in medical schools; and

• Increase communication between conventional and alternative medical professionals.

Neither conventional (i.e., Western) medicine nor alternative medicine can cure all our ills. However, now 

that we have access to therapeutic modalities from different cultures and philosophies, it is the responsibility 

of all medical practitioners to work together to improve on what we have today.
Workshop Agenda and Participant Roster

DoubleTree Hotel Philadelphia

Philadelphia, Pennsylvania

September 25-27, 1996

AGENDA

WEDNESDAY, SEPTEMBER 25, 1996

PREMEETING ACTIVITIES: A PUBLIC HEARING

1:00-6:00 p.m. Public Testimony: The Women’s Health Research Agenda for the 21st Century

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health, NIH, and Director, ORWH

1. Continuing or Emerging Gaps in Knowledge About Women’s Health

Task Force 

2. Successful Models for the Recruitment, Retention, Re-entry, and/or Advancement 

of Women in Biomedical Careers

Task Force 

6:00-7:30 p.m. Meeting with Task Force/Ad Hoc Working Group and Workshop Cochairs

Dr. Pinn

THURSDAY, SEPTEMBER 26, 1996

WORKSHOP DAY 1

Continuing and Emerging Scientific Issues for Women’s Health Research: 

Influence of Sex and Gender on Health

8:30 a.m. Workshop Welcoming Remarks and Overall Charge for the Conference

Dr. Pinn

191

VOLUME 4

BEYOND HUNT VALLEY: 

RESEARCH ON WOMEN’S HEALTH

FOR THE 21 S T CENTURY
192

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Introduction of Conference Cochairs

Donna Dean, Ph.D.

Acting Chief, Referral and Review Branch, Division of Research Grants, NIH

Marianne Legato, M.D.

Associate Professor of Clinical Medicine, Columbia University

College of Physicians and Surgeons

Introduction of Host Institution Cochairs

Jeane Ann Grisso, M.D., M.Sc.

University of Pennsylvania, School of Medicine

Bonita Falkner, M.D.

Professor of Medicine and Pediatrics, Institute for Women’s Health

Allegheny University of the Health Sciences

Overview: Beyond Hunt Valley: Research on Women’s Health for the 21st Century

Charge to Working Groups 

Dr. Pinn

Task Force Cochairs

Logistical Instructions

Local Cochairs

Dr. Grisso

Dr. Falkner

9:45 a.m. Break

10:00 a.m. Concurrent Breakout Working Groups

Consider overarching health issues of aging, chronic disease, the molecular bases for male 

and female differences in disease, behavioral and prevention strategies, risk factors for 

major health issues, gender, diversity, and the environmental impact on women’s health.

GROUP 1. CARDIOVASCULAR DISEASE AND VASCULAR BIOLOGY

The role of gender in angiogenesis, vascular remodeling, cell structure and function, 

and thrombosis. Linkage with sex hormones and cardiovascular disease, diabetes, 

stroke, obesity, and role of nutrition.

GROUP 2. NEUROSCIENCE AND BEHAVIOR

The role of sex and gender in neurodevelopment, CNS structure and function. Linkage 

with sex hormones and cognitive function, perimenopausal cognition, aging cognition, 

eating disorders, and the impact of environmental exposures in women.

GROUP 3. IMMUNOLOGY, GROWTH, AND DEVELOPMENT

The role of sex and gender in inflammation and immune response. Linkage with sex 

hormones, aging, arthritis, and lupus. Role of sex, gender, signaling, and growth factors.
193

VOLUME 4

GROUP 4. INFECTIOUS DISEASES AND EMERGING INFECTIONS

Role of sex and gender in the etiology, transmission, course, and outcomes of infectious 

diseases, including HIV, STDs, and others involving emerging pathogens, with a focus 

on improved prevention, diagnosis, and treatment for women.

GROUP 5. MENTAL AND ADDICTIVE DISORDERS

The role of sex and gender in the etiology, course, comorbidity, and outcomes of mental 

and addictive disorders, including sex hormones, genes, gene-environment interactions, 

gender-related risk behaviors, depression, and eating disorders.

GROUP 6. REPRODUCTIVE HEALTH

Research to address life span issues including research on contraception (development, 

use, and post marketing evaluation), (IOM report), as well as the influence of contraceptive choice on infertility, STDs, (IOM report), acute and chronic conditions, and lifestyle. 

Consider particularly implantation, maternal issues, prevention, diagnosis, treatment 

of pregnancy complications and embryo or fetal loss and reducing morbidity from myoma,

endometriosis, abnormal uterine bleeding, uterine prolapse, and other benign gynecologic 

diseases. Address hormone replacement therapy, menarche, menopause, postmenopausal

issues, and cultural, ethnic, socioeconomic, and behavioral issues.

GROUP 7. CANCER

Address basic science, genetics, gender differences, and environmental factors contributing 

to mortality in breast, lung, colon, and gynecological cancers to understand the malignant

processes and to lead to improved prevention, diagnosis, and treatment. Consider female 

populations that bear a disproportionate burden of cancer incidence and mortality. Ethical, 

legal, and social implications of new technologies including screening and genetic testing.

Noon Lunch Remarks 

Jo Ivey Boufford, M.D.

Principal Deputy Assistant Secretary for Health

U.S. Department of Health and Human Services

1:30 p.m. Working Groups (continued)

3:30 p.m. Break

3:45 p.m. Plenary Keynote Speaker

Nancy Wexler, Ph.D.

Higgins Professor of Neuropsychology, Columbia University

4:15 p.m. Working Group Summary Reports

5:30 p.m. Adjourn

6:00 p.m. Reception
194

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

FRIDAY, SEPTEMBER 27, 1996

WORKSHOP DAY 2

Continuing and Emerging Scientific Issues for Women’s Health Research: 

Research Strategies

8:30 a.m. Kickoff Speaker

Ruth L. Kirschstein, M.D.

Deputy Director, NIH

9:00 a.m. Plenary Session 

Models for the Conduct of Research on Women’s Health: Research Strategies and Methods

9:30 a.m. Charge to the Working Groups: The Future for Women’s Health Research

9:45 a.m. Break

10:00 a.m. Concurrent Breakout Working Groups

Consider overarching issues of life span, aging, prevention, diversity, and collaborative and 

multidisciplinary approaches. The impact of managed care, informatics, and what is ready 

for testing and commercial application should be considered as well as socioeconomic, cultural, 

and sex and gender factors in the identification of unique barriers for:

A. RESEARCH DESIGNS

1. Multidisciplinary Perspectives: How can synergy between scientific disciplines be 

achieved through a multidisciplinary perspective that incorporates biomedical, 

psychosocial, and socioeconomic approaches to women’s health research?

2. Cultural Diversity: How can diverse communities of women participate actively 

in helping set research priorities, participate in clinical studies, and, most importantly, benefit from the implementation of the outcomes. Communities refer to 

different levels of social organization, from families to neighborhoods, and to other

forms of community. How can cultural and socioeconomic factors be differentiated

from race and incorporated into the study of health and disease of women? Culture

refers to shared values and beliefs about the world. Epidemiologic analyses of health

outcomes in diverse populations should also be addressed.

3. Gender: What are the best ways of conceptualizing and studying similarities and 

differences between males and females? As examples, effects might be due to genetics, sex-related hormones, gender role socialization, and disparities in power and

status in society between women and men.
195

VOLUME 4

B. HEALTH IMPACT AND HEALTH OUTCOMES

1. Biotechnical Advances: How can advances in biotechnology be incorporated into 

clinical care and health professional education programs for women’s health, 

including prevention, screening, and treatment? The role of gender in access to 

care, diagnostic and therapeutic interventions, and patient-provider communication should be considered. What are the ethical, legal, and social issues? How 

can the diverse community of women benefit from state-of-the-art research?

2. Gender Differences: How can knowledge of gender differences across the life span 

be applied to preventative interventions? Consideration should be given to what 

constitutes successful life course transitions (entrance to school, adolescence, 

entrance to parenthood, widowhood).

C. WOMEN IN BIOMEDICAL CAREERS: ISSUES OF IMPORTANCE FOR 

YOUNG INVESTIGATORS

Positive ways to advance women’s careers through training, leadership opportunities, and mentorship. What are successful examples of recruitment, retention, 

re-entry, and advancement?

12:15 p.m. Break

12:30 p.m. Lunch

Keynote Speaker

Karen Davis, Ph.D.

President, The Commonwealth Fund

1:45 p.m. Plenary (Working Group Reports)

3:30 p.m. Closing Remarks and Adjournment

Dr. Pinn

197

VOLUME 4

PHILADELPHIA, PENNSYLVANIA

SEPTEMBER 25-27, 1996

PARTICIPANTS

Dyanne Affonso, Ph.D., F.A.A.N.

Dean and Professor

Nell Hodgson Woodruff School of Nursing

Emory University

Atlanta, Georgia 

Graciela Alarcon, M.D., M.P.H.

Professor of Medicine

Associate Director Arthritis Center University 

of Alabama

Birmingham, Alabama 

Judith Albert, M.D.

Assistant Professor

Department of Obstetrics, Gynecology, and 

Reproductive Sciences

University of Pittsburgh School of Medicine

Division of Reproduction Endocrinology

Magee-Womens Hospital

Pittsburgh, Pennsylvania 

Nancy Alexander, Ph.D.

Chief, Contraceptive Development Branch

Center for Population Research

National Institute of Child Health and 

Human Development 

National Institutes of Health

Bethesda, Maryland 

Ann Anderson, Ph.D.

Acting Dean

Tulane University School of Public Health 

and Tropical Medicine

New Orleans, Louisiana 

Karen Antman, M.D.

Professor of Medicine, Columbia University

Chief, Division of Medical Oncology

Columbia Presbyterian Comprehensive Cancer Center

New York, New York 

Deborah Armstrong, M.D.

Assistant Professor of Oncology

Johns Hopkins Hospital

Medical Oncology

Baltimore, Maryland 

Constance Atwell, Ph.D.

Associate Director, Extramural Activities

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Bethesda, Maryland 

Byllye Avery

Founder

Associate Director for Government Affairs

National Black Women’s Health Project

Swarthmore, Pennsylvania 

Anne R. Bavier, M.N., F.A.A.N.

Deputy Director

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland

Consuelo Beck-Sagué, M.D.

Associate Director for Minority and Women’s Health

National Centers for Infectious Diseases

Centers for Disease Control and Prevention

Atlanta, Georgia 

Michelle Berlin, M.D., M.P.H.

Assistant Professor of Obstetrics and Gynecology, 

and Epidemiology

Center for Clinical Epidemiology and Biostatistics

University of Pennsylvania

Philadelphia, Pennsylvania 

Janet Bickel

Assistant Vice President for Institutional 

Planning and Development

Association of American Medical Colleges

Washington, District of Columbia 

Stephanie Bird, Ph.D.

Special Assistant to the Provost

Massachusetts Institute of Technology

Cambridge, Massachusetts 

Mary Blehar, Ph.D.

Chief, Mood, Anxiety, and Personality 

Disorders Research Branch

Division of Clinical and Treatment Research

National Institute of Mental Health

National Institutes of Health

Rockville, Maryland 

Beyond Hunt Valley: 

Research on Women’s Health for the 21ST Century
198

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Sandra Bloom, M.D.

Executive Director, The Sanctuary, Friends Hospital

President-Elect, International Society for 

Traumatic Stress Studies

Quakertown, Pennsylvania 

Mark Boyd, Ph.D.

Department of Oncology

Allegheny University of the Health Sciences 

Center City

Philadelphia, Pennsylvania 

Patricia Braly, M.D.

Professor

Chief, Section of Obstetrics and Gynecology

Louisiana State University Medical Center

New Orleans, Louisiana 

Edward Brandt, Jr., M.D., Ph.D.

Regents Professor and Director

Center for Health Policy

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 

Otis Brawley, M.D.

Director

Office of Special Populations

National Cancer Institute

National Institutes of Health

Rockville, Maryland 

Isadore Brodesky, M.D.

Chair, Hematology/Oncology

Allegheny University of the Health Sciences 

Center City

Philadelphia, Pennsylvania 

Sandra Brooks, M.D.

Director, Division of Gynecologic Oncology

Department of Obstetrics and Gynecology

University of Maryland School of Medicine

Baltimore, Maryland 

Carol Brown, M.D.

Clinical Assistant Surgeon, Gynecological Service

Department of Surgery

Memorial Sloan-Kettering Cancer Center

New York, New York 

Zora Brown

Founder and Chair

Breast Cancer Resource Committee

Washington, District of Columbia 

George Bryan, M.D.

Dean Emeritus, School of Medicine

The University of Texas Medical Branch

Galveston, Texas 

Virginia Cain, Ph.D.

Special Assistant to the Director 

Office of Behavioral and Social Sciences Research 

Office of the Director

National Institutes of Health

Bethesda, Maryland 

Richard Cannon III, M.D.

Deputy Chief for Clinical Services

Cardiology Branch

National Heart, Lung, and Blood Institute 

National Institutes of Health

Bethesda, Maryland 

Arthur Caplan, Ph.D.

Director, Center for Bioethics

University of Pennsylvania

Philadelphia, Pennsylvania 

Wendy Chavkin, M.D., M.P.H.

Editor-in-Chief

Journal of the American Medical Women’s Association

Beth Israel Medical Center

Chemical Dependency Institute

American Medical Women’s Association, Inc.

New York, New York 

Mary T. Chunko, M.A.

Information Development Specialist

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland

Marilee Comfort, Ph.D., M.P.H.

Research Director

Family Center

Thomas Jefferson University

Philadelphia, Pennsylvania 

Helen Coons, Ph.D.

Director of Evaluation

Health Federation of Philadelphia

Philadelphia, Pennsylvania 

George Counts, M.D.

Director, Office of Research on Minority 

and Women’s Health

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland 
199

VOLUME 4

Terri Damstra, Ph.D.

Associate Director for Science Coordination 

National Institute of Environmental Health Sciences 

National Institutes of Health 

Research Triangle Park, North Carolina 

Alice Dan, Ph.D.

Professor

Center for Research on Women and Gender

University of Illinois at Chicago

Chicago, Illinois 

Karen Davis, Ph.D.

President

The Commonwealth Fund

New York, New York

Donna Dean, Ph.D.

Acting Chief

Referral and Review Branch

Division of Research Grants

National Institutes of Health

Bethesda, Maryland

Betty Diamond, M.D.

Professor

Department of Microbiology and Immunology, 

and Medicine

Albert Einstein College of Medicine

Bronx, New York 

Kay Dickersin, Ph.D.

Associate Professor

Department of Epidemiology

University of Maryland at Baltimore

Baltimore, Maryland 

Leah Dickstein, M.D.

Professor

Department of Psychiatry and Behavioral Sciences

School of Medicine

University of Louisville

Louisville, Kentucky 

Catherine Didion

Executive Director

Association for Women in Science

Washington, District of Columbia 

Andrea Dunaif, M.D.

Senior Director, Diabetes Medical Research

Parke-Davis Medical Research

Parke-Davis Building 79-2

Morris Plains, New Jersey 

Jacqueline Dunbar-Jacob, Ph.D., R.N., F.A.A.N. 

Professor and Director

Center for Research and Chronic Disorders

School of Nursing

University of Pittsburgh

Pittsburgh, Pennsylvania 

Carola Eisenberg, M.D.

Lecturer in Psychiatry

Dean for Student Affairs (Retired)

Harvard Medical School

Cambridge, Massachusetts 

Tom Eng, V.M.D., M.P.H.

Senior Program Officer 

Institute of Medicine

Washington, District of Columbia

Donald Faber, Ph.D.

Chair, Anatomy

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Bonita Falkner, M.D.

Professor of Medicine and Pediatrics

Institute for Women’s Health 

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Loretta Finnegan, M.D. 

Director, Women’s Health Initiative

National Institutes of Health

Bethesda, Maryland 

Leslie Ford, M.D.

Associate Director 

Early Detection and Community Oncology Program

Division of Cancer Prevention and Control

National Cancer Institute

National Institutes of Health

Bethesda, Maryland 

Michael Fordis, M.D.

Director

Office of Education

National Institutes of Health

Bethesda, Maryland

Patricia Fraser, M.D., M.P.H.

Assistant Professor of Medicine

Director, Pediatric Rheumatology

Brigham and Women’s Hospital

Boston, Massachusetts 
200

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

William Freeman, M.D., M.P.H.

Research Director

Indian Health Service 

Public Health Service

U.S. Department of Health and Human Services

Albuquerque, New Mexico 

Maria Freire, Ph.D.

Director

Office of Technology Transfer

National Institutes of Health

Bethesda, Maryland 

Bruce Fuchs, Ph.D. 

Acting Director

Office of Science Education

National Institutes of Health

Bethesda, Maryland 

Sheryle Gallant, Ph.D.

Associate Professor of Psychology

Department of Psychology

University of Kansas

Lawrence, Kansas 

Sarah Garber, Ph.D.

Associate Professor of Physiology

Department of Physiology

Allegheny University of the Health Sciences

MCP – Hahnemann University School of Medicine

Philadelphia, Pennsylvania 

Marilyn Gaston, M.D.

Assistant Surgeon General

Director

Bureau of Primary Health Care

Bethesda, Maryland 

W. Lou Glasse, M.S.W.

President Emerita

Older Women’s League

Vassar College

Poughkeepsie, New York 

John Glick, M.D.

Director

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania 

Irma Goertzen

President and Chief Executive Officer

Magee-Women’s Hospital

Pittsburgh, Pennsylvania 

Eileen Gorman, Ph.D.

Senior Research Associate

Dade Chemistry Systems

Newark, Delaware 

Patricia Grady, Ph.D.

Director

National Institute of Nursing Research

National Institutes of Health

Bethesda, Maryland 

Phyllis Greenberger, M.S.W.

Executive Director

Society for the Advancement of Women’s 

Health Research

Washington, District of Columbia 

Jeane Ann Grisso, M.D., M.Sc.

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania 

Raquel Gur, M.D., Ph.D.

Professor and Director of Neuropsychiatry

Department of Psychiatry

University of Pennsylvania

Philadelphia, Pennsylvania 

Ruben Gur, Ph.D.

Director

Brain Behavior Laboratory

University of Pennsylvania

Philadelphia, Pennsylvania 

Betty Hambleton

Women’s Health Coordinator

Health Resources and Services Administration

Rockville, Maryland 

Della Hann, Ph.D.

Chief

Interpersonal and Family Processing Program

National Institute of Mental Health

National Institutes of Health

Rockville, Maryland 

Hazel Harper, D.D.S.

Hazel Harper & Associates

Washington, District of Columbia 

Janet Henrich, M.D.

Associate Professor of Medicine and Gynecology

Primary Care Center

Yale University School of Medicine

New Haven, Connecticut
201

VOLUME 4

Enrique Hernandez, M.D.

Professor and Director of Gynecologic Oncology

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Penelope Hitchcock, D.V.M.

Chief, Sexually Transmitted Diseases Branch

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland

Eileen Hoffman, M.D.

Assistant Professor of Medicine

Associate Director for Education

Mount Sinai Women’s Health Program

New York, New York

Ann Honebrink, M.D.

Co-Director, Center for Women’s Health

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Marc Horowitz, J.D.

Director, Office of Loan Repayment and Scholarship

Office of Intramural Research

Office of the Director

National Institutes of Health

Bethesda, Maryland

Howard Hu, M.D., Sc.D.

Associate Professor of Occupational Medicine

Channing Laboratory

Boston, Massachusetts

Carole Hudgings, Ph.D.

Program Officer

Office of Alternative Medicine

National Institutes of Health

Bethesda, Maryland

Joseph Hurd, Jr., M.D.

Chairman, Department of Gynecology

Lahey Hitchcock Clinic

Burlington, Massachusetts

Debbie M. Jackson, M.A.

Program Analyst

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland 

Sharon Jackson, M.D.

Clinical Researcher

Laboratory of Host Defense

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland 

Dara Jamieson, M.D.

Department of Neurology

Pennsylvania Hospital

Philadelphia, Pennsylvania 

Marlene Jasperse

Research Specialist

Navajo Division of Health

Navajo Research Program

Window Rock, Arizona

Katrina Johnson, Ph.D.

Research Program Officer

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland 

Wanda Jones, Dr.P.H.

Assistant Director for Women’s Health

Centers for Disease Control and Prevention

Atlanta, Georgia 

Barbara Karp, M.D.

Associate Clinical Director

National Institute of Neurological Disorders 

and Stroke

National Institutes of Health

Bethesda, Maryland 

Gwendolyn Keita, Ph.D.

Director, Women’s Program Office

American Psychological Association

Washington, District of Columbia 

M. Margaret Kemeny, M.D.

Chief, Division of Surgical Oncology

Department of Surgery

North Shore University Hospital 

Manhasset, New York 

Mi Ja Kim, Ph.D.

Vice Chancellor for Research

Dean of the Graduate College

University of Illinois at Chicago

Chicago, Illinois 

Ruth L. Kirschstein, M.D.

Deputy Director

National Institutes of Health

Bethesda, Maryland 

Barbara Konkle, M.D.

Associate Professor of Medicine

Cardeza Foundation for Hematologic Research

Thomas Jefferson University 

Philadelphia, Pennsylvania 
202

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Howard Kurtzman, Ph.D.

Chief, Cognitive Science Program

National Institute of Mental Health

National Institutes of Health

Rockville, Maryland

Demie Kurz, M.D.

Co-Director, Women’s Studies

University of Pennsylvania

Philadelphia, Pennsylvania 

Ruth Lamdan, M.D.

Assistant Professor of Psychiatry

Department of Psychiatry

Allegheny University of Health Sciences 

Philadelphia, Pennsylvania 

Marianne Legato, M.D.

Associate Professor of Clinical Medicine 

Columbia University College of Physicians 

and Surgeons

New York, New York 

Ellen Leibenluft, M.D.

Chief, Unit on Rapid-Cycling Bi-Polar Disorder

Clinical Psychopharmacology Branch

National Institute of Mental Health

National Institutes of Health 

Bethesda, Maryland 

Matthew Levison, M.D.

Chair, Infectious Disease

Allegheny University of the Health Sciences 

Philadelphia, Pennsylvania 

Sissel Lund-Katz, Ph.D.

Professor

MCP – Hahnemann School of Medicine

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Joanne Luoto, M.D., M.P.H.

Medical Officer

Contraceptive and Reproductive Evaluation Branch

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Jennifer Madans, Ph.D.

Acting Associate Director of Vital and Health Statistics

National Center for Health Statistics

Hyattsville, Maryland 

Yvonne Maddox, Ph.D.

Deputy Director

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Worta McCaskill-Stevens, M.D.

Assistant Professor of Medicine

Indiana University

University Hospital

Indianapolis, Indiana 

Catherine McDermott

President and Chief Executive Officer

Grantmakers In Health

Washington, District of Columbia

Sonja McKinlay, Ph.D.

President

New England Research Institutes, Inc.

Watertown, Massachusetts 

Ruth Merkatz, Ph.D., R.N., F.A.A.N.

Senior Advisor to the Commissioner

Women’s Health Issues

Office of Women’s Health

Food and Drug Administration

Rockville, Maryland 

Sherry Mills, M.D., M.P.H.

Cancer Control Research Scientist

Prevention and Control Extramural Branch

National Cancer Institute

National Institutes of Health

Bethesda, Maryland 

Howard Minkoff, M.D.

Professor of Obstetrics and Gynecology

Director of Maternal-Fetal Medicine

Department of Obstetrics and Gynecology

Health Science Center at Brooklyn

State University of New York

Brooklyn, New York 

Donnica Moore, M.D.

Associate Director

Medical Education Center

Sandoz Pharmaceuticals

Neshanic Station, New Jersey 

Diane Morel, Ph.D.

Assistant Professor of Biochemistry

Biochemistry Department

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 
203

VOLUME 4

Mary Morrison, M.D.

Assistant Professor of Psychiatry and Medicine

Department of Psychiatry

University of Pennsylvania

Philadelphia, Pennsylvania 

Donna Murasko, Ph.D.

Professor and Acting Chair

Department of Microbiology and Immunology

MCP – Hahnemann University School of Medicine

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Roberta Ness, M.D., M.P.H.

Assistant Professor of Epidemiology and 

Women’s Health Programs

Graduate School of Public Health

University of Pittsburgh

Pittsburgh, Pennsylvania 

Susan Newcomer, Ph.D.

Statistician (demography)

Demographic and Behavioral Sciences Branch

Center for Population Research

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Christine Maguth Nezu, Ph.D.

Associate Provost for Research

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Judy Norsigian

Co-Director

Boston Women’s Health Book Collective

Somerville, Massachusetts 

Joel Noumoff, M.D.

Director, Division of Gynecologic Oncology

Vice-Chair, Department of Obstetrics and Gynecology

Crozer Chester Medical Center

Upland, Pennsylvania 

Bonnie O’Conner, Ph.D.

Community and Preventive Health

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Suzanne Oparil, M.D.

Director, Vascular Biology and Hypertension Program

Division of Cardiovascular Disease

University of Alabama at Birmingham

Birmingham, Alabama

Nancy Padian, Ph.D.

Associate Professor

Department of Obstetrics, Gynecology 

and Reproductive Science

University of California at San Francisco

San Francisco General Hospital

San Francisco, California

Delores Parron, Ph.D.

Associate Director for Special Populations

National Institute of Mental Health

National Institutes of Health

Rockville, Maryland

Estella Parrott, M.D., M.P.H.

Coordinator of Research Programs

Office of Research on Minority and Women’s Health

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland

Jane Pearson, Ph.D.

Chief, Clinical and Developmental PsychoPathology Program

Mental Disorders of the Aging Research Branch

National Institute of Mental Health

National Institutes of Health

Rockville, Maryland 

Connie Perry, Ph.D.

Department of Humanities, Social Services, 

and Biometrics

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania

Vivian W. Pinn, M.D.

Director

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland 

Anthony Piraino, Ph.D.

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania

Jerome Platt, Ph.D.

Professor and Director

Division of Addiction Research and Treatment

Department of Psychiatry

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania
204

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Ellyn J. Pollack, M.A., APR

Information Officer

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland 

Linda Pottern, Ph.D.

Epidemiologist

Women’s Health Initiative

National Institutes of Health

Bethesda, Maryland

Daniel Rader, M.D.

Associate Program Director

General Clinical Research Center

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania

E. Albert Reece, M.D.

Abraham Roth Professor and Professor of 

Internal Medicine

Chairman of Obstetrics and Gynecology

Department of Obstetrics and Gynecology

Temple University School of Medicine

Philadelphia, Pennsylvania 

Eddie Reed, M.D.

Chief, Clinical Pharmacology Branch

National Cancer Institute

National Institutes of Health

Bethesda, Maryland 

David Robinson, Ph.D.

Program Director

National Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland 

Roxanne Rodney, M.D.

Assistant Professor of Clinical Medicine

Associate Director of Nuclear Cardiology

Division of Cardiology

Columbia University

New York, New York 

Helen Rodriguez-Trias, M.D.

Co-Director, Pacific Institute for Women’s Health

Western Consortium for Public Health

Los Angeles, California 

Judith Ross, M.D.

Professor

Department of Pediatrics

Thomas Jefferson University

Philadelphia, Pennsylvania 

Joyce Rudick

Senior Program Analyst

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland 

Sheryl Ruzek, Ph.D., M.P.H.

Professor of Health Education

Department of Health Education and 

Women’s Studies

Temple University

Philadelphia, Pennsylvania 

Rosalie Sagraves, Pharm.D.

Dean and Professor

University of Illinois at Chicago 

College of Pharmacy

Chicago, Illinois 

Gloria Sarto, M.D., Ph.D.

Professor and Chairperson

Department of Obstetrics and Gynecology

University of New Mexico

Albuquerque, New Mexico 

Anne Sassaman, Ph.D.

Director

Division of Extramural Research and Training

National Institute of Environmental Health Sciences

National Institutes of Health

Research Triangle Park, North Carolina 

Priscilla Schaffer, Ph.D.

Professor and Chair

Department of Microbiology 

University of Pennsylvania School of Medicine 

Philadelphia, Pennsylvania 

Susan Schwartz-Giblin, Ph.D.

Department of Medicine

Allegheny University of the Health Sciences 

Philadelphia, Pennsylvania 

Susana Serrate-Sztein, M.D.

Director, Arthritis Program

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

National Institutes of Health

Bethesda, Maryland 

Valerie Setlow, Ph.D.

Director, Division of Health Sciences Policy

Institute of Medicine

National Academy of Sciences

Washington, District of Columbia 
205

VOLUME 4

Moira Shannon, Ed.D., R.N.

Nurse Consultant

Health Resources and Services Administration 

Division of Nursing

U.S. Department of Health and Human Services

Rockville, Maryland 

Eleanor Shore, M.D., M.P.H.

Dean for Faculty Affairs

Harvard Medical School

Boston, Massachusetts 

Marjorie Shultz, J.D., M.A.T.

Professor of Law

Boalt Hall School of Law

University of California at Berkeley

Berkeley, California 

Susan Sieber, Ph.D.

Deputy Director

Division of Cancer Epidemiology and Genetics 

National Cancer Institute

National Institutes of Health

Bethesda, Maryland 

Jamie Siegel, M.D.

Assistant Professor

Medicine and Pathology and Laboratory Medicine 

Division of Hematology/Oncology

Allegheny University of the Health Sciences 

Philadelphia, Pennsylvania 

Elin Sigurdson, M.D., Ph.D.

Director, Surgical Research

Fox Chase Cancer Center

Philadelphia, Pennsylvania 

Emil Skobeloff, M.D.

Department of Emergency Medicine

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Gail Slap, M.D.

Director of Adolescent Medicine

Division of General Internal Medicine

University of Pennsylvania

Philadelphia, Pennsylvania 

Sheryl Smith, Ph.D.

Associate Professor

Department of Neurobiology and Anatomy

Allegheny University of the Health Sciences 

Center City Campus

Philadelphia, Pennsylvania 

Virginia Stallings, M.D.

Chief, Nutrition Section

Division of Gastroenterology and Nutrition 

The Children’s Hospital of Philadelphia 

Philadelphia, Pennsylvania 

Sharilyn Stanley, M.D.

Special Assistant for Science Policy

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Bethesda, Maryland 

Ora Strickland, Ph.D.

Independence Professor

Nell Hodgson Woodruff School of Nursing

Emory University

Atlanta, Georgia 

Brian Strom, M.D., M.P.H.

Chair, Department of Biostatistics and Epidemiology

Director, Center for Clinical Epidemiology 

and Biostatistics

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania 

Anne Summer, M.D.

Assistant Professor

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Ramona Tascoe, M.D., M.H.S.A.

Oakland, California 

Rosemary Torres, J.D., R.N.

Attorney

Sedro Woolley, Washington 

Edward Trimble, M.D., M.P.H.

Head, Surgery Section

Cancer Therapy Evaluation Program

Division of Cancer Treatment, Diagnosis, and Centers

National Cancer Institute

National Institutes of Health

Bethesda, Maryland 

Thomas Tulenko, Ph.D.

Allegheny University of the Health Sciences

Philadelphia, Pennsylvania 

Donald Vereen, Jr., M.D., M.P.H. 

Special Assistant for Medical Affairs 

National Institute on Drug Abuse 

National Institutes of Health

Rockville, Maryland 
206

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Frances Visco, J.D.

President

National Breast Cancer Coalition

Philadelphia, Pennsylvania 

Donna Vogel, M.D., Ph.D.

Associate Chief for Clinical Research

Reproductive Sciences Branch 

Center for Population Research

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Eugene Washington, M.D., M.P.H., M.Sc.

Professor and Chair

Department of Obstetrics and Gynecology

University of California at San Francisco

San Francisco, California 

Anita Corman Weinblatt, Ph.D.

Scientific Review Administrator

Division of Research Grants

National Institutes of Health

Bethesda, Maryland 

Constance Weinstein, Ph.D.

Health Scientist Administrator

National Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland 

Cora Lee Wetherington, Ph.D.

Women’s Health Coordinator

National Institute on Drug Abuse

National Institutes of Health

Rockville, Maryland 

Nancy S. Wexler, Ph.D.

Higgins Professor of Neuropsychology

Department of Neurology and Psychiatry

College of Physicians and Surgeons

Columbia University

New York, New York 

Judith M. Whalen

Associate Director for Science Policy

Analysis and Communication

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Anne Willoughby, M.D., M.P.H.

Chief

Pediatric, Adolescent, and Maternal AIDS Branch

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Nancy Fugate Woods, Ph.D., R.N., F.A.A.N.

Professor, University of Washington

Director, Center for Women’s Health Research

School of Nursing

Seattle, Washington

Susan Yanovski, M.D.

Director, Obesity and Eating Disorders Program

National Institute of Diabetes and Digestive 

and Kidney Diseases

National Institutes of Health

Bethesda, Maryland 

Darlene Yee, Ed.D., C.H.E.S.

Professor and Director, Gerontology Programs

Former Chair, Committee for the Protection 

of Human Subjects

San Francisco State University

San Francisco, California 

Elizabeth Young, M.D.

Associate Professor Psychiatry

Associate Research Scientist

Mental Health Research Institute

Ann Arbor, Michigan 

Richard Zaino, M.D.

Professor of Pathology

Milton S. Hershey Medical Center

Hershey, Pennsylvania
207

VOLUME 4

A

abnormal uterine bleeding 64, 66, 193

abuse

child 40, 53, 55, 58

physical 49, 53, 55, 58, 65, 166

sexual 40, 49, 53, 55, 58, 66, 113

addiction

alcohol 13, 48, 52–53, 57, 59

drugs 49, 56, 58

aging 101, 112, 141, 150, 161, 164, 192, 194

AIDS 37–39, 42, 49, 52, 55, 59, 62–63, 83, 87, 

92, 99–100, 105, 107, 109, 152–53, 155–56,

160–61, 168, 172

allergic diseases 25–27

Alzheimer’s disease 19–20, 22, 112, 133, 160

anemia 26, 30, 64, 77

antigens 27–28, 31, 34

antioxidants 13

anxiety 19, 47, 49–51, 54, 56, 58, 71, 143

aspirin 10, 13, 78, 187

asthma 26, 28

atherogenesis 13

autoimmune diseases 25–27, 29–32, 83, 130, 

134–35, 137–38, 150, 158–59, 161, 175

B

bacterial vaginosis 45, 62, 166

body image 51, 75

C

cancer

breast 9–11, 13, 15–16, 45, 53, 57, 59, 61, 64,

71–72, 74–77, 83, 87, 90, 101, 107, 109,

133, 147, 160, 165, 171, 176, 180, 193

cervical 31, 38, 71–73, 75–78, 133, 171, 193

colorectal 71–72, 77–78, 187, 193

endometrium 71, 75–77, 90, 187

Kaposi’s sarcoma 71, 78

lung 71–74, 78, 193

lymphoma 71, 78

melanoma 78

nasopharyngeal 71–72

ovary 1, 65, 71–72, 75, 77, 87, 133, 187, 193

cardiovascular disease

anginal syndromes 10, 15, 151

arrhythmias 15, 150

arteriosclerosis 26

ischemia 13, 15, 151

cerebrovascular disease 14–15, 150

chemotherapy 28, 74–78

cholesterol 11–13, 92, 148, 177

chronic fatigue syndrome 45, 113

chronic pain 19, 21, 143

clinical practice guidelines 108

clinical trials 3, 11, 31–34, 40, 43–44, 68, 74–75, 

77, 79, 89, 97–102, 106–07, 127, 160, 185

cognition 19–22, 192

compliance 39–40, 44, 68, 99

contraceptives 29, 31, 44, 63, 65, 68, 75–77, 

101, 133, 137, 154, 158, 177

cultural competence 112–13

cultural relevance 112

D

depression (see mental disorders)

diabetes 10, 12–14, 16, 20, 26, 28, 30, 64, 75, 

113, 139, 142, 148, 150–51, 177, 192

disability 9, 137, 146, 164, 172

diversity 59, 87–88, 90, 93, 107, 165, 173, 

182, 192, 194

INDEX
208

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

E

early fetal loss 37

ectopic gestation 62–63, 65, 68

epilepsy 19–20, 22, 135

Epstein-Barr virus 71

estrogen 10–17, 19–22, 28–30, 50, 53–54, 

57–59, 63, 66, 74–76, 78, 90, 100, 

132–37, 140–41, 148, 150, 187

estrogen replacement therapy (ERT) 11, 14, 

16, 20, 28, 53, 57, 59, 75, 78, 140, 148

F

fibromyalgia 32

G

gender differences 4, 10, 14, 17, 19–22, 30, 

47, 49–50, 53–59, 97, 100–01, 108, 111, 

122, 138–39, 148, 174, 193, 195

gender sensitivity 117, 144

genetics 71–72, 77, 108, 139, 187, 193–94

Graves’ disease 26, 30, 158

H

hepatitis 26, 30, 39–40, 45

high blood pressure 14, 32, 55, 148, 176

HIV 37–45, 49, 52, 55–56, 59, 62–63, 76–78, 

83, 92, 94, 105, 107, 109, 152–56, 160, 

163–64, 166–69, 171–72, 193

homeless 112–14, 180

hormone replacement therapy (HRT) 10–11, 15, 61,

66, 83, 101, 140, 148, 151, 160, 193

human papilloma virus (HPV) 38–40, 42, 71, 76, 78

hypertension 12, 17, 87, 93, 100, 112–13, 143, 

150, 176–77

hysterectomy 66, 75–77, 98, 130, 150

I

immune response 25–31, 76, 134–35, 138, 192

immune system 25–28, 30–31, 42, 134–35, 138, 158

immunology 13, 22, 25, 33–35, 37, 65, 119, 181,

187, 192

incarceration 40

inclusion 2–3, 47, 68, 88–90, 92–93, 97–99, 

101–02, 109, 163, 170

incontinence 44

infectious disease 13, 25–27, 31, 37, 40–45, 

62, 163, 193

infertility 37, 39, 42, 63–68, 133, 185, 193

informed consent 35, 99, 107, 130

institutional review board 92, 101, 107

interferon 27–28

irritable bowel syndrome 113, 187

L

lesbians 4, 94, 112–13, 163–73

life cycle 41, 183

life transition points 111

lipid metabolism 12

lupus 14, 26, 28–30, 32, 34–35, 135, 150, 

158, 192

M

managed care 5, 10, 33–35, 41, 67, 79, 98, 

108–09, 128, 173, 194

menstruation

cycle 19, 22, 30, 42, 52, 54, 56, 58, 98, 

100–01, 135, 137–38, 187

menarche 31, 157, 193

menopause 11–12, 19–20, 31, 34, 41, 61, 

63, 75, 98, 132–33, 139–40, 142, 148, 

150, 157, 193

mental disorders

anxiety 19, 47, 49–51, 54, 56, 58, 71, 143

bi-polar 50

depression 14, 19–20, 22, 32, 47–48, 50–51,

56–59, 65, 73, 101, 113, 133, 164, 166, 

185, 193

phobias 49, 51, 112, 166, 171–72

schizophrenia 19–20, 22, 47

mentoring 118–21, 131, 162, 170, 187

microbicides 39, 42–43, 63, 65, 76

migrant 112–14

mucosal immunity 27, 31, 34

multidisciplinary research 32, 34, 81–85
209

VOLUME 4

multiple sclerosis 19, 22, 26–28, 30–31, 35, 113, 

135, 158, 160

myasthenia gravis 26, 113, 135, 137

N

neurochemistry 19, 21

neuroimaging 21

neuropsychoimmunology 28, 32

neurotransmitters 28

nutrition 16, 29, 62, 132, 141, 144, 180, 192

O

obesity 10, 12, 14–15, 17, 75, 148–50, 192

oral health 139–40, 142, 144

osteoarthritis 29

osteoporosis 28, 32, 53, 57, 59, 75, 101, 111,

132–33, 139, 141–42, 160, 186

ovarian failure 63, 66, 68

P

Pap smear 76, 166, 171

Parkinson’s disease 19

pelvic inflammatory disease 38–39, 63

pharmacokinetics 55–56, 65, 68, 100, 102, 139

physician training 34

polycystic ovarian disease 20, 61, 64, 66, 68, 150

polyposis 78

posttraumatic stress disorder (PTSD) 51, 54, 56,

58–59, 113

practice-based community research 114

pregnancy 21, 27, 30–31, 34, 37–45, 48, 55, 57, 

62, 65–68, 75, 77, 100–01, 106, 134–38, 140,

149, 157–60, 164, 185, 187, 193

premenstrual syndrome (PMS) 61, 64, 66–67

prevention 9–10, 12–13, 16, 28, 31, 37, 39–45, 

49, 53, 56, 58, 62, 72–79, 92, 105, 107, 

112–14, 127, 132–33, 138–40, 142, 144, 

147, 151, 156, 159, 166–67, 169–72, 

174–75, 178–79, 186–87, 192–95

progesterone 19–20, 62, 75–76, 100, 134–35, 

140, 187

progestin 11–12, 16, 133, 148

puberty 16, 30, 34, 41, 51, 136, 140, 148, 

154, 157

Q

quality of life 38, 66–67, 72, 75, 77–78, 93, 

105, 186

R

race 9, 43, 48, 65, 74, 88, 92–94, 132, 147, 

164, 171, 176, 179–80, 182, 194

rape 51, 55, 179

reproductive conditions

endometriosis 61, 64, 66, 68, 133, 193

myoma 64, 66, 68, 193

ovarian failure 63, 66, 68

pelvic floor relaxation 64, 66

uterine fibroids 61, 133, 150

rheumatic heart disease 9, 30, 147

risk behaviors 55, 166, 193

risk factors 11–17, 29, 32, 38, 40, 43, 52, 58, 

62, 66, 68–69, 75, 77, 101, 111, 127, 132, 

141, 143, 148–50, 153–56, 164, 177, 179, 

182, 192

S

schizophrenia (see mental disorders)

septicemia 45

serotonin 19

sexual issues

discrimination 97, 117–19, 122, 150, 164

harassment 117–20

practices 55, 154

sexually transmitted diseases (STD) 37–44, 49, 

61, 63, 68, 76, 107, 112, 133, 152–56, 160, 

164, 166, 193

sigmoidoscopy 78
210

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

smoking 10, 12, 14–16, 62, 66, 72–73, 76, 78, 

92, 100, 132, 144, 148, 150, 167, 177

socioeconomic status (SES) 33, 56, 59, 89, 91, 

97, 139–40, 143, 153, 155, 182

spina bifida 62

stress 29, 48–51, 54, 56, 58–59, 79, 113, 134, 

136, 139–40, 142–44, 179

stroke 9, 12–15, 17, 19–21, 133, 146–48, 150–52,

176–77, 188, 192

T

tamoxifen 72, 74–75

technology transfer 105–06

thyroid disease 32, 148

toxic shock syndrome 45

transplantation 17, 28, 75

tubal scarring 39–40

tuberculosis 44

U

ultrasound 63, 75, 77, 106

urinary tract infections (UTI) 44

V

vaccines 26–27, 31, 40, 42–44, 76

vaginal ecosystem 37–39, 41–42

vertical transmission 38, 40, 42–43, 55

victimization 53–55

violence 50, 53, 55, 58, 83, 94, 101, 113–14, 

166, 180–81, 183
211

VOLUME 4

ORD ER FORM

Agenda for Research on Women’s Health for the 21st Century is a 6-volume report from four scientific meetings 

and public hearings to establish an agenda for women’s health research for the 21st century. Volume 1 contains the executive summary and volume 2 is a composite report containing recommendations from all four

meetings. Volume 3 contains public testimony from the Bethesda, Maryland meeting, and volumes 4, 5, and 6 are

reports and public testimony from the three regional meetings and public hearings. To order a single, free copy 

of each volume, please indicate which publication(s) you would like to receive.

 Volume 1 — Agenda for Research on Women’s Health for the 21st Century, A Report of the Task Force on the NIH

Women’s Health Research Agenda for the 21st Century, Executive Summary; NIH Publication No. 99-4385.

 Volume 2 — Agenda for Research on Women’s Health for the 21st Century, A Report of the Task Force on the NIH

Women’s Health Research Agenda for the 21st Century; NIH Publication No. 99-4386.

 Volume 3 — Agenda for Research on Women’s Health for the 21st Century, Public Testimony; Bethesda, Maryland:

November 1997; NIH Publication No. 99-4387.

 Volume 4 — Agenda for Research on Women’s Health for the 21st Century, Influences of Sex and Gender on Health;

Philadelphia Scientific Meeting and Public Hearing, September 1996; NIH Publication No. 99-4388.

 Volume 5 — Agenda for Research on Women’s Health for the 21st Century, Sex and Gender Perspectives for Women’s 

Health Research; New Orleans Scientific Meeting and Public Hearing, June 1997; NIH Publication No. 99-4389.

 Volume 6 — Agenda for Research on Women’s Health for the 21st Century, Differences Among Populations of

Women; Santa Fe, New Mexico, Scientific Meeting and Public Hearing, July 1997; NIH Publication No. 99-4390.

Name _________________________________________________________________________

Title ___________________________________________________________________________

Affiliation _______________________________________________________________________

Address ________________________________________________________________________

_______________________________________________________________________________

Telephone Number ___________________________ Email ______________________________

 Please check here if you would like to be added to the Office of Research on Women’s Health mailing list.

Please mail or fax this completed form to: Office of Research on Women’s Health, Office of the Director, National

Institutes of Health, 1 Center Drive, Room 201, MSC 0161, Bethesda, Maryland 20892-0161; fax: 301-402-1798.


NIH Publication No. 99-4388