VOLUME 5

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

SEX AND GENDER PERSPECTIVES

FOR WOMEN’S HEALTH RESEARCH

Scientific Meeting and Public Hearing

New Orleans, Louisiana

June 1997

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 5

Hosted by:

Tulane University Medical Center

Xavier University

Meharry Medical College

SEX AND GENDER PERSPECTIVES

FOR WOMEN’S HEALTH RESEARCH

Scientific Meeting and Public Hearing

New Orleans, Louisiana

June 1997
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 5. Sex and Gender Perspectives for 

Women’s Health Research. Bethesda, MD. NIH Publication No. 99-4389. 1999.
I

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

convened a meeting in Hunt Valley, Maryland, to assess the state of the science of women’s health and to

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

meeting, Report of the 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 develop researchbased 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 heath; 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 the 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

iii

VOLUME 5

PREFACE
iv

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

from the three regional public hearings and scientific workshops and developed the recommendations 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 participated in the process and 

continue to provide guidance and expertise to ORWH.

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

the scientific workshops, the plenary presentations, 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 Philadelphia and Santa Fe and at the 

national meeting in Bethesda.
PREFACE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iii

ACKNOWLEDGMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vii

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

Vivian W. Pinn, M.D.

WORKING GROUP REPORTS

Sex and Gender Perspectives for Women’s Health Research through the Life Cycle

Prenatal, Infancy, and Childhood Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11

Denise Granado-Villar, M.D.; David Robinson, Ph.D.; Joan Spyker-Crammer, Ph.D.; Kathleen Gasparian

Adolescent Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Susan Abdalian, M.D.; Thomas Lasater, Ph.D.; Anne Willoughby, M.D., M.P.H.; Ann Morcos, M.A., E.L.S.

Reproductive and Middle Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

Linda Alexander, Ph.D.; Gwen W. Collman, Ph.D.; Gloria Richard-Davis, M.D.; Angela Lorio

Perimenopausal and Postmenopausal Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

Anuradha V. Rao, M.D.; Sherry Sherman, Ph.D.; Sarah Moody Thomas, Ph.D.; Miriam Y. Miller

Elderly and Frail Elderly Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35

Mary C. Dufour, M.D., M.P.H.; Carola Eisenberg, M.D.; W. Lou Glasse, M.S.W.; Veronica J. Scott, M.D., M.P.H.; 

Gillian Brown

PLENARY PRESENTATIONS

Why Women? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43

Michael D. Lockshin, M.D.

Psychological Differences Between Women and Men: Implications for a Research Agenda on Women’s 

Physical and Mental Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .54

Vickie M. Mays, Ph.D.

The Pharmacologic Differences Between Women and Men . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .65

Raymond L. Woosley, M.D., Ph.D.

PUBLIC Testimony

Introduction to the Public Testimony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71

Testimonies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73

WORKSHOP AGENDA AND PARTICIPANT ROSTER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123

INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131

C O NTENTS

VOLUME 5

vii

VOLUME 5

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 New Orleans, 

and for their assistance in bringing this meeting to fruition.

Our regional cochairs for this meeting included Dr. Judith H. LaRosa, Professor and Chair of the Department 

of Applied Health Sciences at the Tulane University School of Public Health and Tropical Medicine. Dr. LaRosa 

also served as the first Deputy Director of the Office of Research on Women’s Health at NIH. Second is Dr. John 

J. Estrada, who is a member of the national Advisory Committee on Research on Women’s Health at NIH and an

Assistant Professor of Pediatrics and Microbiology at Meharry Medical College, where he also serves as Director 

for Pediatric Education and Chair of the Faculty Senate. We are pleased to have with us Mrs. Sybil Haydel Morial,

Associate Vice President for Public Affairs and Communications at Xavier University of Louisiana, also a valued

cosponsor of this meeting. Additional people who were instrumental in planning this public hearing and scientific

workshop were Dr. Anne Anderson, Melinda Epperson, and Roz Lewy of the Tulane University Medical Center.

It was a great pleasure to have with us Dr. John LaRosa, Chancellor of the Tulane University Medical Center. 

In addition to his current esteemed position, Dr. LaRosa has long been in the forefront of research on women’s

health and health care, being an internationally recognized expert on cholesterol, coronary disease, and cardiovascular disease in women. He is also the former Dean for Clinical Affairs and Dean for Research at The George

Washington University School of Medicine and Health Sciences in Washington, D.C. 

This meeting was planned with the assistance of a great number of other individuals. Of our ORWH office

staff, let me first acknowledge Ms. Joyce Rudick, who is the Acting Deputy Director of our Office, and who has

tirelessly devoted her leadership to the development and implementation of these meetings to revise our research

agenda. She has provided the heart and soul, as well as the elbow grease, to make these meetings occur, and to 

her we owe a special appreciation. 

Our efforts to revisit our research agenda were led by our Task Force on the NIH Women’s Health Research

Agenda for the 21st Century. We were fortunate to have members of the NIH scientific community, as well as

women’s health advocates, scientists and health professionals from across the country serving as members of 

this important Task Force.

Our Task Force, which oversaw this workshop and the report generated from it, was cochaired by Dr. Donna

Dean and Dr. Marianne Legato; we are so grateful for their dedicated leadership. Dr. Donna Dean, Acting Chief 

of the Referral and Review Branch, Division of Research Grants at NIH, is a member of the Coordinating Committee for Research on Women’s Health, the advisory body to our office, which is composed of the Directors or

their designee of the institutes, centers, and divisions of NIH. Dr. Dean is also Chair of the Research Subcommittee, which provides guidance to our office about our priorities and funding programs. Dr. Marianne Legato,

who is a member of our Advisory Committee on Research on Women’s Health and a noted expert on cardiovascular diseases of women, has recently established a center for women’s health at Columbia University College 

of Physicians and Surgeons. 

ACKNOWLEDGMENTS
viii

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

I would also like to acknowledge the participation in this meeting of Dr. Loretta Finnegan, Director of the

Women’s Health Initiative, one of the largest prevention studies ever conducted, which is examining the role of 

hormone replacement therapy, dietary modification, Vitamin D and calcium supplementation, and behavioral 

modification in the prevention of the major causes of death and frailty in postmenopausal women (i.e., cardiovascular disease, cancer, and osteoporotic fractures).

We also acknowledge and thank the individuals serving in the following groups:

•Task Force on the NIH Women’s Health Research Agenda for the 21st Century

•Advisory Committee on Research on Women’s Health

•Coordinating Committee on Research on Women’s Health

•Cochairs of the Working Groups at the regional meeting in New Orleans, Louisiana

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
ix

VOLUME 5

COCHAIRS

Donna Dean, Ph.D.

Acting Chief of the Referral and Review Branch

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 Francisco, 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

Hazel Harper and Associates

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 H. 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.

Prevention and Control Extramural 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

Neshamic 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

Research Triangle Park, North Carolina

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 (Retired)

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
xi

VOLUME 5

Roster, 1997

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

Joyce Rudick

Acting 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

Maywood, Illinois 

Carol A. Aschenbrener, M.D.

Senior Scholar in Residence

Association of Academic Health Centers

Washington, District of Columbia

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

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma 

David M. Brown, M.D.

Professor of Pediatrics, Laboratory Medicine, 

and Pathology

Head, Division of Pediatric Endocrinology

School of Medicine

Division of Pediatric Endocrinology

University of Minnesota

Minneapolis, Minnesota 

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

Director

AMC 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

W. Lou Glasse, M.S.W.

President Emerita

Older Women’s League

Vassar College

Poughkeepsie, New York

Irma E. Goertzen

President and Chief Executive Officer

Magee-Women’s Hospital

Pittsburgh, Pennsylvania 

Joseph K. Hurd, M.D.

Chairman

Department of Gynecology

Lahey Clinic Medical Center

Burlington, Massachusetts 

Barbara A. Koenig, Ph.D.

Senior Research Scholar

Executive Director

Stanford University Center for Biomedical Ethics

Palo Alto, California

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

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

Associate Professor of Clinical Medicine

College of Physicians and Surgeons of

Columbia University

New York, New York

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

Distinguished Professor and Dean

Indiana University School of Nursing

Indianapolis, Indiana

Linda C. Niessen, D.M.D., M.P.H.

Professor and Chair

Department of Public Health Sciences

Baylor College of Dentistry

Dallas, Texas

Amelie G. Ramirez, Dr.P.H.

Associate Professor

Associate Director

Center for Cancer Control Research

Baylor College of Medicine

Houston, Texas

Nancy Sabin Wexler, Ph.D.

Higgins Professor of Neuropsychology

College of Physicians and Surgeons of 

Columbia University

New York, New York
xiii

VOLUME 5

COORDINATING COMMITTEE ON RESEARCH ON 

WOMEN’S HEALTH 

NATIONAL INSTITUTES OF HEALTH

Roster, June 1997

Norman Anderson, Ph.D.

Director

Office of Behavioral and Social Sciences Research

Office of the Director 

Tina Blakeslee

Legislative Liaison and Analysis Branch

Office of the Director

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

Fogarty International Center

Virginia Cain, Ph.D.

Special Assistant to the Director

Office of Behavioral and Social Sciences Research

Office of the Director 

Joan Chamberlin

Information Officer

Division of Computer Research and Technology

Paul Coates, Ph.D.

Program 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 

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

Deborah Dozier-Hall

Assistant to Chief for Education

Clinical Center

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

Officer of Equal Opportunity

Office of the Director 

Loretta Finnegan, M.D.

Director

Women’s Health Initiative

Julia Freeman, Ph.D.

Director

Centers Program

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

Harriet Gordon

Medical Officer

General Clinical Research Centers Program

National Center for Research Resources

Robin Hamilton

Program Analyst

National Institute of Neurologic Disorders and Stroke

Eleanor Hanna, Ph.D.

Special Expert

Division of Biometry and Epidemiology

National Institute on Alcohol Abuse and Alcoholism 

J. Taylor Harden, Ph.D. 

Assistant to the Director for Special Populations

National Institute on Aging
xiv

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

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 

Caroline Holloway

Health Scientist Administrator

Biomedical Technology

National Center for Research Resources

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 Scientist Administrator

Division of Human Communication 

National Institute on Deafness and Other 

Communication Disorders

Laura James

Nurse Science Administrator

National Institute for Nursing Research

Walter Jones

Deputy Director of Management and Operations

Warren Grant Magnuson Clinical Center

Bonnie Kalberer

Special Assistant

Office of Science Policy

Office of the Director

Barbara Kellner

Technical Information Specialist

National Institute on Aging

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

Office of Science and Technology 

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

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

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 

Sherman Ragland, Ph.D.

Deputy Associate Director for Special Populations

National Institute of Mental Health

Mary Ann Robinson

Senior Scientist

National Institute of Allergy and Infectious Diseases

Adele Roman, M.S.N.

Deputy Women’s Health Coordinator

National Institute on Drug Abuse
xv

VOLUME 5

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 Extramural Research

Office of the Director

Sandra Smith-Gil

Senior Scientist

National Cancer Institute

Susan Stark

Writer-Editor

Planning Office

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

Mary Stephens-Frazier

Health Scientist Administrator

National Institute of Nursing Research

Patricia Straat, Ph.D.

Deputy Chief for Referral

Division of Research Grants

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

National Institute of Child Health and 

Human Development

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

Associate Director for Science Policy, Analysis, 

and Communication

National Institute of Child Health and Human 

Development

Susan Wise

Program Analyst

Planning & Legislation Section

National Institute of Dental Research

Chris Zimmerman

Program Analyst 

National Institute of General Medical Sciences

xvii

VOLUME 5

Research Subcommittee Roster, June 1997

COCHAIRS

Donna Dean, Ph.D. 

Chief, Biological and Physiological Systems

Division of Research Grants

David Robinson, Ph.D. 

National Heart, Lung, and Blood Institute

OFFICE OF RESEARCH ON WOMEN’S HEALTH

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

Joyce Rudick

Acting Deputy Director

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

COORDINATING COMMITTEE ON RESEARCH 

ON WOMEN’S HEALTH 

NATIONAL INSTITUTES OF HEALTH

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Career Development Subcommittee Roster, June 1997

COCHAIRS

Anne Sassaman, Ph.D.

National Institute of Environmental Health Sciences

Julia Freeman, Ph.D.

National Institute of Arthritis and Musculoskeletal 

and Skin Diseases

OFFICE OF RESEARCH ON WOMEN’S HEALTH

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

Director, Office of Research on Women’s Health

Joyce Rudick

Acting Deputy Director

Office of Research on Women’s Health 

COMMITTEE MEMBERS

Jim Alexander, Ph.D.

Office of Education

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

COORDINATING COMMITTEE ON RESEARCH 

ON WOMEN’S HEALTH 

NATIONAL INSTITUTES OF HEALTH

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INTRODUCTION 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

This was the second of a series of regional

workshops and scientific meetings during

which the Office of Research on Women’s

Health of the National Institutes of Health had 

an opportunity to learn about the public’s and 

scientific community’s visions of the Women’s 

Health Research Agenda for the 21st Century.

The public testimony and the recommendations

developed by the working groups assisted us in reexamining the existing NIH agenda for women’s health

research. Utilizing scientific directives in a sciencedriven agenda, we assessed our current priorities, with

the assistance of our Task Force on the NIH Women’s

Health Research Agenda for the 21st Century and the

Advisory Committee on Research on Women’s Health,

which are composed of non-federal scientists, health

care providers, educators, and women’s health advocates. 

Recommendations from the scientific workshops

allowed us to direct, or redirect, our future endeavors

in such a way that the knowledge that we have gained

through biomedical and behavioral research, and the

momentum our collective efforts have generated, can

be used to protect and improve the health and well

being of girls and women.

It was a wonderful opportunity for us from NIH

to meet with people in New Orleans. This would not

have been possible without the leadership and efforts

of our regional hosts, the Tulane University Medical

Center, Xavier University of Louisiana, and Meharry

Medical College. We are grateful to them for their

efforts on our behalf to facilitate the participation 

of so many people in this process. 

The major charge during this workshop was to

help determine future directions for women’s health

research and its related issues. There is no question

that research is central to providing the scientific foundation for change, and that new knowledge resulting

from research can provide the basis for the improved

health of girls and women.

There must be a multidisciplinary collaboration,

with multiple partners sharing the responsibility to

establish and disseminate new information resulting

from increased and enhanced research on women’s

health, to implement its findings into standards of

health care delivery, and to influence the behavior 

and health practices of not only the scientific and 

medical communities but also of individual women 

and their families.

If research on and about women is to change 

with the times and respond to continuing and emerging gaps in knowledge, there must be a coalition of

effort involving all segments of the scientific and 

health care communities, federal agencies, women’s

health advocacy groups, and, most importantly,

women and their families and communities. And, 

history has demonstrated that the efforts of these

groups, in harmony and concerted effort, have 

brought about a change.

We owe much change to the many individuals,

groups, and organizations dedicated to improving the

health of women, such as the Boston Women’s Health

Book Collective, the National Women’s Health Network, the National Black Women’s Health Network,

the Society for the Advancement of Women’s Health

Research, among many others. They have been working in the “trenches,” so to speak, to call attention to

the need to focus our attention on women’s health. 
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

It is only recently that the efforts of the Federal

Government have recognized women’s health as a 

real issue requiring a real remedy, and today, because 

of the efforts of advocates and scientists, we are beginning to make progress.

PHS TASK FORCE 

AND ESTABLISHMENT 

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 made 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 most pertinent recommendations 

of the Task Force report was one that 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.1

Dr. Brandt stated that, as Assistant Secretary for

Health, “I am committed to seeing that this report

results in action that is beneficial to the women of

America...” Thus began the federal initiatives that 

continue to address women’s health.

HISTORY OF INCLUSION

POLICIES AT NIH

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, but also received its 

initial impetus from the recommendations of the Task

Force appointed by Dr. Brandt, of which Dr. Ruth

Kirschstein, currently the Deputy Director of NIH,

served as cochair for more than 10 years. Following 

the issuance of the report of the PHS Task Force on

Women’s Health 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 1987 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

requested a General Accounting Office (GAO) investigation of the implementation by NIH of the guidelines

for the inclusion of women. In 1990, this GAO report

stated that implementation of the policy for the inclusion of women was lacking, that implementation was

slow and not well communicated, that gender analysis

was not implemented, and that the impact of policy

could not be determined.2

In September 1990, just 3 months after the release

of the GAO report, the subsequent media coverage 

and public reaction catalyzed the establishment of the

Office of Research on Women’s Health (ORWH) at

NIH. The Office was established to serve as the focal

point for women’s health research at NIH in a collaborative partnership with the institutes and centers.

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.

In 1993, ORWH was legislatively mandated in 

the NIH Revitalization Act. It was this congressional

language that also mandated that we establish a 

Coordinating Committee on Research on Women’s
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Health, to be composed of the Directors of the NIH

institutes, divisions, and centers, and an Advisory

Committee on Research on Women’s Health, to be

composed of non-federal employees who are 

experts on women’s health.

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

and, although there is still much to be accomplished, 

we have made some progress.

NIH MANDATE FOR THE

INCLUSION OF WOMEN

AND MINORITIES IN

CLINICAL RESEARCH

ORWH has assumed leadership in implementing

policies requiring the inclusion of women and minorities in human subject research. Wanting to assure 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 NIH Revitalization Act of 1993, entitled, “Women and Minorities

as Subjects in Clinical Research.”

The NIH 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 in

March 1994,3 and they have been fully implemented.

We have established a tracking system to monitor

inclusion. For the first time, we are able to determine the numbers of women and minorities in 

clinical trials, and, as we begin to analyze data 

from studies active in FY 1995, establish trends 

in inclusion and determine better ways to examine 

this data.

We have found a high compliance with the 

inclusion policy. Analysis of FY 1994 NIH enrollment data showed that substantial numbers of 

both women and minorities have been recruited 

as research subjects. The goal of NIH policy is not 

to satisfy quotas for proportional representation, 

but rather to conduct biomedical and behavioral

research in such a manner that the scientific 

knowledge acquired will be generalizable to 

the entire population.

We also funded the Institute of Medicine study,

Women in Health Research, an excellent report on the

legal and ethical issues related to women, especially

women of childbearing age, in human subject research.

However, as we have moved from being cognizant of

regulations established to protect women and minorities and other populations from being exploited in

research, and to respond to the tragedies witnessed 

in the Tuskegee syphilis study and on the effects of

those exposed to DES and thalidomide in utero, we

still must grapple with the very important issues of

women of childbearing age in clinical research and 

the issues of protection of women and their potential 

offspring as the risks versus benefits are weighed.

We firmly believe that the implementation of 

the NIH policy for the inclusion of women and minorities in human subject research requires the increased

participation of women and minority physicians and

scientists in the design, implementation, and interpretation of such studies.
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

WOMEN IN 

BIOMEDICAL CAREERS

To determine best directions to increase opportunities for women in biomedical research careers, we

held a public hearing and workshop on the recruitment, retention, advancement, and re-entry of women

in biomedical careers to determine barriers to women’s

success and how to overcome these barriers. A number

of barriers were identified in the report from our Task

Force on Women in Biomedical Careers, for which the

cochairs were Drs. Carola Eisenberg and Shirley Malcolm. Following the recommendations of this report,

we have established a number of programs, including

our re-entry program to address the loss of women

whose dual roles as care givers led to an interruption 

of their research careers. We also put into place a 

number of other initiatives to develop the careers of

women and men scientists in research on women’s

health, including workshops on how to speak and

write about science.

Under the leadership of Joyce Rudick, Dr. Anne

Sassaman, and Dr. Julia Freeman, cochairs of the

Career Development Subcommittee of our Coordinating Committee on Research on Women’s Health, 

we have evaluated the re-entry program, and we are

now looking for ways to best expand our other initiatives. As an integral part of our regional meetings, 

we focused on recommendations to assist us with

future program planning.

NIH NATIONAL

RESEARCH AGENDA 

ON WOMEN’S HEALTH

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. The NIH Office of Research on Women’s

Health 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 

see how far we have come.

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 current agenda began

with the Hunt Valley report, National Institutes of Health:

Opportunities for Research on Women’s Health.

This agenda was formulated from a public hearing

and workshop held in September 1991 in Hunt Valley,

Maryland, from which the parameters of women’s

health have been redefined, and research has been 

redirected to provide better information on sex and

gender differences between women and men in development, health and disease, and to focus on populations of women that have been underrepresented 

in clinical research.

Our agenda recognizes the full spectrum of

research from basic to clinical research and trials, 

epidemiological and population studies, clinical applications, and health outcomes. We have embraced the

expanded concepts of women’s health and research 

to address the health of girls and women across the 

life span. We are recognizing that women’s health

encompasses more than the reproductive system, and

that research does involve the entire spectrum and not

just human subject research. We also expanded our

boundaries of the life span to take into account the

health of women from the prenatal stage to that of 

the frail elderly — the divisions of the working 

groups that convened during this meeting.

The research agenda includes biomedical as well 

as behavioral and psychosocial research. We have

incorporated as an integral part of our research priorities that we must reach out to populations of women

and girls who have been previously excluded from 

scientific investigation, such as minorities, women 

of differing socioeconomic status and geographic 

locations, lesbians, and women with disabilities. 

In all our efforts to implement our research agenda, 

we are in an active and beneficial partnership with 

all NIH institutes, divisions, and centers. We constantly review our research priorities to determine

where the major gaps in knowledge exist.
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As a part of our efforts to address implementation

of women’s health research and its incorporation into

the standards of health care practice, and promoting

multidisciplinary, comprehensive, and effective women’s

health care, we collaborated with the Health Resources

and Services Administration (HRSA) and the Public

Health Service Office of Women’s Health to prepare 

a report of surveys of all osteopathic and allopathic

schools of medicine to determine the extent of women’s

health in their curricula. This report also contains

examples of model women’s health curricula. We are

now working with dental, nursing, and pharmacy

school representatives to initiate a similar study of 

their educational curricula.

In 1991, the Hunt Valley meeting led to our 

current working research document. We believe that 

it is time to look “beyond Hunt Valley” and to update

our agenda. We found that the model of broad participation in this process through public hearings 

and workshops with representative and voluntary 

participation worked well and have thus turned 

again to this model to help us in the current process.

This mechanism provides an opportunity for continued collaboration among individuals, groups of

women, advocates, scientists, health care practitioners, and pubic health policymakers with NIH 

to establish our research agenda as we move 

forward into the 21st century.

Our research agenda currently focuses on sex 

and gender factors in the health and diseases of 

women in considering such matters as normal development, disease prevention, health maintenance,

response to interventions, disease prognosis, and 

treatment outcomes. We have also focused on factors

that influence differences in health status and health

outcomes among different populations of women.

Beginning in September 1996, at our first regional

meeting in Philadelphia, we began the process of reexamining our research agenda to ensure that it is 

relevant as we move towards the next century. At the

Philadelphia meeting we directed attention to some 

of the major areas of concern for women’s health.

At this meeting in New Orleans, we looked at 

two of the ways to examine knowledge about women’s

health: sex and gender factors and differences among

populations of women. Therefore, during the scientific

workshop, we examined aspects of the research agenda

based upon sex and gender perspectives. Our plenary

presentations examined whether sex and gender differences are due only to hormones, and we looked at the

impact of environmental factors and genetic information on the health and well being of women. The specific objectives of this 2-day meeting were to:

• Assess the current status of research on women’s

health and identify gaps in knowledge.

• Identify factors that may influence health status,

including physiological, psychosocial, and pharmacologic differences that exist between women

and men.

• Address emerging issues across the research spectrum from basic studies to clinical and applied

research, with special focus on the effects of environmental hazards and toxins across the life span.

• Develop strategies based on research that can 

result in an improved health status for all women,

regardless of race, ethnicity, or age.

At the third and last regional meeting held in 

Santa Fe, New Mexico, in July 1997, and hosted by 

the University of New Mexico Medical Center and the

University of Iowa School of Pharmacy, we focused on

factors that contribute to differences in health status

and health outcome among different populations of

women, including biology, genetics, race, culture and

ethnicity, psychosocial and behavioral factors, educational influences, traditional and alternative practices,

environment, poverty and socioeconomic status, 

access to health care, and occupation.

Finally, in November 1997, we brought together

the results of all three regional meetings in a national

workshop in Bethesda, Maryland, to provide an opportunity for our participants to guide our Task Force in

developing recommendations for the NIH research 
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

agenda for the beginning of the 21st century. We asked

the working groups to develop their reports within the

following parameters. 

• 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.

• Generate recommendations for future research 

priorities and necessary consideration of the 

biomedical and 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.).

• Consider how, where, and in what manner to 

best assure implementation of the results of 

our advances in knowledge from research.

All of our programs and initiatives should be 

science driven. Our updated agenda must reaffirm 

the commitment to integrate 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

assistance, as we enter the 21st century, ORWH can

build on that power and maximize its power to improve

the health of women and their families. That is the

vision for women’s health in the United States and

beyond. No single individual or group can do the 

job alone. The challenge — and the responsibility 

— must be shared by all of us.

References

1 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.

2 Nadel, M.V. National Institutes of Health: Problems in Implementing Policy on Women in Study Populations. Washington,

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

3 Department of Health and Human Services, National

Institutes of Health. NIH Guidelines on the Inclusion of

Women and Minorities as Subjects in Clinical Research;

Notice. Federal Register. DHHS/NIH/Part VIII. Vol. 59, 

no. 59 (March 28, 1994):14508–14513.
Working Group Reports

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VOLUME 5

BEYOND HUNT VALLEY: 

RESEARCH ON WOMEN’S HEALTH FOR THE 21ST CENTURY

NEW ORLEANS, LOUISIANA

JUNE 12–13, 1997

SEX AND GENDER PERSPECTIVES FOR 

WOMEN’S HEALTH RESEARCH

WORKING GROUP COCHAIRS

PRENATAL, INFANCY, AND CHILDHOOD YEARS

Daisy Granado-Villar, M.D.

Director of Preventive Medicine Health

Promotion Division

Miami Children’s Hospital

Miami, Florida

David Robinson, Ph.D.

Director, Vascular Research Program

National, Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland

Joan Spyker-Crammer, Ph.D.

Professor of Pediatrics and Toxicology

University of Arkansas for Medical Sciences

Department of Pediatrics at Arkansas

Children’s Hospital

Little Rock, Arkansas

ADOLESCENT YEARS

Susan Abdalian, M.D.

Associate Professor of Clinical Pediatrics

Department of Adolescent Medicine

Tulane University Medical School

New Orleans, Louisiana

Thomas Lasater, Ph.D.

Director, Division of Research

Center for Primary Care and Prevention

Memorial Hospital of Rhode Island

Pawtucket, Rhode Island

Anne Willoughby, M.D., M.P.H.

Chief, Pediatric, Adolescent and Maternal AIDS Branch

Center for Research for Mothers and Children

National Institute of Child Health and Human 

Development

National Institutes of Health

Bethesda, Maryland

REPRODUCTIVE AND MIDDLE YEARS

Linda Alexander, Ph.D.

Vice President for Women’s Health

United Information Systems, Inc.

Bethesda, Maryland

Gwen W. Collman, Ph.D.

Scientific Programs Administrator

Division of Extramural Research and Training

National Institute of Environmental Health Sciences

National Institutes of Health

Bethesda, Maryland

Gloria Richard-Davis, M.D.

Assistant Professor Obstetrics-Gynecology

Tulane University Medical Center

New Orleans, Louisiana 

PERIMENOPAUSAL AND POSTMENOPAUSAL YEARS

Anuradha V. Rao, M.D.

Director, Women’s Heart Program

Clinical Instructor of Medicine

Department of Medicine

Tulane University Medical Center

New Orleans, Louisiana 

Sherry Sherman, Ph.D.

Director, Endocrine and Osteoporosis Research

National Institute on Aging

National Institutes of Health

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

Sarah Moody Thomas, Ph.D.

Associate Director

Stanley Scott Cancer Center

Louisiana State University Medical Center

New Orleans, Louisiana

ELDERLY AND FRAIL ELDERLY YEARS

Mary C. 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 for Student Affairs (Retired)

Harvard Medical School

Boston, Massachusetts

W. Lou Glasse, M.S.W.

President Emerita

Older Women’s League

Vassar College

Poughkeepsie, New York

Veronica J. Scott, M.D., M.P.H.

Associate Professor

Director, Center on Aging

Meharry Medical College

Nashville, Tennessee
Prenatal, Infancy, 

and Childhood Years

BACKGROUND

The breadth of the prenatal through early

puberty stage of the life cycle is the first challenge in addressing women’s health concerns.

Throughout these stages, development occurs rapidly

and not necessarily according to a preordained time table.

Devising a standard, applicable method of stratification with useful and meaningful categories, without

using extensive testing, is essential. Because human

development during these life stages is rapid and

diverse, a method of stratification that uses chronology

exclusively is not desirable; behavioral and psychological factors must be included. For research into this

stage of women’s life cycle, the following nondiscreet

stratification is recommended as a guideline:

• Preconception. Includes the external and internal

influences on the mother and the father, and the

effects that these influences will have on the child.

• Embryonic/fetal development. Includes the substrata

of gene expression, implantation, and more minute

divisions of the current trimester partitions.

• After birth. Includes a chronological division tempered with behavioral and psychological development

that extends the stratification to six subcategories:

newborn, infant, toddler, preschool-aged child,

early school-aged child, and preadolescent.

Within this stratification, research should be 

clarified according to gender and ethnic and cultural

backgrounds whenever possible.

Gaps in knowledge about normal biological development processes constitute the second challenge facing

the study of this stage of the life cycle. More information

is needed about the early stages of prenatal development

and of behavioral, social, and physical development

throughout this period of life.

The third obstacle facing study of this area of

women’s health is the number of external and internal

factors involved from preconception through early

puberty. The influences and effects of these factors

throughout a woman’s life are monumental and difficult to single out. With these obstacles in mind, education and prevention must be emphasized to promote

overall wellness, beginning with the preconception

stage and extending through childhood.

RESEARCH 

RECOMMENDATIONS

Normative Development

The working group sessions repeatedly mentioned

the lack of knowledge concerning normative development of the fetus and the child. Basic biological research

is needed concerning the prenatal through early puberty

Cochairs

Denise Granado-Villar, M.D.

Miami Children’s Hospital

David Robinson, Ph.D.

National Heart, Lung, and Blood Institute 

National Institutes of Health

Joan Spyker-Crammer, Ph.D.

University of Arkansas for Medical Sciences

Rapporteur: Kathleen Gasparian

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

stages of life, because understanding normative development allows for a clearer understanding of pathological

processes. Research into normative development needs

to be stratified according to developmental stage, gender, and ethnicity. A multidisciplinary approach that

includes the social, environmental, behavioral, and

physical aspects of development is recommended as

the best approach for research. Recommended 

research topics in this area include:

• Gene expression and the interaction of the 

environment with genes.

• Implantation and the first trimester development,

including gender differences in development.

• Normative placental function and the function 

of the placenta as a protective barrier.

• Development of organ systems using a multidisciplinary approach. This research should include 

but not be limited to dentition, the cardiovascular

system, the central nervous system, the endocrine

system, and the impact of prenatal events on 

development.

• The impact of and the gender differences in

response to stress and nutrition in this stage 

of the life cycle.

• Determination of the critical developmental periods

and the critical periods of sensitivity to environmental factors during this stage of the life cycle.

• Regulation of normal labor and the mechanisms 

of preterm labor.

• Importance and effect of preconception health, plus

how to disseminate this information effectively.

PHARMACOKINETIC/

PHARMACODYNAMIC

EFFECTS OF DRUGS IN

NONADULT, NONMALE

POPULATIONS

Gaps in knowledge exist about the effects of 

prescription and over-the-counter medications, xenobiotics, and herbal remedies on women and children.

The effects of a drug on an adult male are not necessarily similar to those experienced by a child, a pregnant

or lactating woman, a fetus, or a breast-feeding infant.

In researching these areas of pharmacokinetics and

pharmacodynamics, a stratification must be adopted

that addresses the differences of age, gender, and 

ethnicity. Recommended topics for research include:

• Absorption, distribution, metabolism, and elimination of drugs. This examination should begin early

in the prenatal stage and follow a system of stratification that takes into account age, weight, and

development through the breast-feeding stage and

early childhood to the beginnings of puberty.

• Biological responses to drugs of the fetus, the

breast-feeding infant, and the prepubescent child.

• Effects of exposure to drugs during critical 

prenatal and perinatal stages of development.

• Long- and short-term effects of drugs on the 

fetus and the child.

PREVENTION AND 

EDUCATION

Prevention and education are key to promoting

overall wellness that extends into adulthood. The data

for prevention and education needs to be acquired in 

a gender- and culture-sensitive manner, and then disseminated appropriately to the intended audience,
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based on culture, gender, and age. Essential to any 

program before implementation is an understanding 

of the steps of prevention and intervention for specific

diseases and behaviors. Education and prevention 

programs must have long- and short-term targets 

in order to produce lasting results.

Recommended research topics in this area include:

• Longitudinal evaluations of preventive strategies, taking into account short- and long-term

behavior changes.

• Rapid dissemination of research results in a 

gender-, culture-, and age-appropriate manner.

• Inclusion of alternative medicine approaches, 

such as massage therapy and homeopathic remedies, in education and prevention programs.

ENVIRONMENTAL

AGENTS

Environmental factors influence wellness in the

prenatal through prepubescent stages of the life cycle.

Toxins associated with industry, water supplies, and

commercial and residential expansion affect health

through nutrition and exposure, threatening the well

being of women and children. Especially for ethnic

minorities, the effects of toxins on women and children

are often overlooked in environmental studies. Topics 

for research in this area include:

• Effects of environmental agents on gene expression.

• Impact of environmental agents on implantation

and first trimester development.

• Effects of environmental agents on placental 

function.

• Effect of the environment on organ systems, including dentition, the cardiovascular system, the central

nervous system, the endocrine system, and the

impact of prenatal events on development.

• Narrow windows of critical periods of exposure to

environmental agents, plus the long- and short-term

consequences of exposure during these windows.

• Critical pathways of exposure, such as nutrition,

lactation, and formula.

• Community-based prevention and research pertaining to environmental exposure and effects.

NORMATIVE GENDERSPECIFIC BEHAVIORAL

AND PSYCHOLOGICAL

DEVELOPMENT

Major gaps exist in our knowledge of normative

behavioral and psychological development. Even at

early ages, the differences in behavior between the 

genders are noticeable, yet this area is lacking in

research and study; studies of behavior often ignore

developmental differences. Recommendations for

research include: 

• Behavioral and psychological attributes of children,

taking into account gender and ethnic differences

and developmental diversity.

• Attributes of the development of health-related

behaviors in children.

• Critical stress points in these stages of the life 

cycle and the development of coping strategies.

GENDER-SPECIFIC

TRANSGENERATIONAL

P ASSAGE OF DISEASE

Additional knowledge about the passage of 

disease from mother to child is needed. Children

become predisposed to diseases in the early stages 

of their development. Topics for research include:
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

• Role of the “programming hypothesis” and 

the effects on women and children.

• Relationship of programming to varied 

physiological systems.

• Functional genomic research.

• Reversal of unwanted prenatal programming.

ETHICAL CONCERNS

Because of the diversity of studies and research

and because of the impact these studies can have on

women, children, and society as a whole, ethical concerns must be studied and evaluated. The following

categories are of concern: surrogate motherhood,

embryo research, fetal research, cloning, genetic testing, genetic records, prenatal gene therapy, storing and

discarding embryos, rights of the fetus and the woman,

fetal surgery, and fetal and neonatal organ donation.

CONCLUSION

The importance and delicacy of this stage of

women’s life cycle cannot be emphasized enough. 

Sensitivity to the mother and the child is required 

in all endeavors that advance our understanding 

of these aspects of women’s health.
ADOLESCENT YEARS 

BACKGROUND

Adolescence is a time of explosive change. 

The body grows and develops faster from

puberty to 18 years than at any other time 

of life except from birth to age 1. Physical growth is 

the most obvious change: children become taller and

heavier, and their facial features become more adultlike. They also gain sexual maturity and become able 

to bear children. Less obvious, but just as important,

are the intellectual and psychological changes that 

take place. Adolescents grow mentally, gaining new

insight and understanding and the ability to com

prehend increasingly complex issues. Psychological

growth helps young people better understand the

changes taking place and how these changes alter 

their overall being. Although physical, intellectual, 

and psychological growth are normal aspects of 

adolescent development, they occur unevenly — 

they are unsynchronized — and can often lead 

to insecurity, anxiety, conflict, risk-taking behavior, 

and other emotional challenges.

The rate of change varies not just between boys

and girls (girls mature faster in all areas than boys do),

but also from individual to individual, race to race, 

and culture to culture (Puerto Rican, Mexican, and

South American girls develop at different rates and 

in different ways from each other in spite of the fact 

that they are all Hispanic). Great diversity exists 

among adolescents. This diversity dramatically affects

developmental processes. One size does not fit all.

ADOLESCENT ISSUES

Maturation

Physical maturity begins at a much earlier age

today than it did a century ago, probably due to

improvements in nutrition, general health, and living

conditions. In the United States, the age of menarche 

has decreased three to four months per decade during

the past 100 years, but has now leveled off. Ironically,

however, although puberty is beginning earlier, the

completion of the transition from adolescence into

adulthood and independence is occurring later. Drug 

use and sexual activity are beginning at an earlier age 

as well. The challenges of adolescence are far greater,

more serious, more complex, and more life threatening than in the past.

Adolescent Pregnancy

Teenage pregnancy is higher in the United States

than in any other industrialized country. More than 

1 million teenaged girls in the United States become

pregnant each year. More than one-third of U.S. girls

become pregnant at least once during adolescence, 

and most of these girls complete their pregnancy. A

third of these girls become pregnant a second time 

during their adolescent years. In many inner city communities, teenage pregnancy is considered epidemic.

In 1987, 472,623 infants were born to U.S. teenagers, an estimated 12 percent of all births. Sixty-four

percent of these infants were born out of wedlock.

Cochairs

Susan Abdalian, M.D.

Tulane University Medical School

Thomas Lasater, Ph.D.

Memorial Hospital of Rhode Island

Anne Willoughby, M.D., M.P.H.

National Institute of Child Health and Human Development

National Institutes of Health

Rapporteur: Ann Morcos, M.A., E.L.S.

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

About 10,311 babies were born to mothers under 15

years of age. About 400,000 therapeutic abortions are

performed on teenagers each year. The divorce rate for

teenage marriages is 50 percent within 2 years and 80

percent by 5 years. Many teenaged mothers have not

done well in school and have a history of psychological

problems. Pregnancy and marriage, stressful enough for

adults, add turmoil to adolescent years at a time when

life is already in flux. Pregnant teens and their partners

usually drop out of school, which increases economic

difficulties, loss of self esteem, and strain on interpersonal relationships. Abortion does not resolve the situation because the psychological distress caused by the

unwanted pregnancy still occurs. Trauma may result

when the pregnancy is diagnosed, when the decision 

to have an abortion is made, during the post-abortion

recovery period, on the date the baby would have 

been born, and on the anniversaries of that date.

Abuse and Neglect

The upheavals taking place during adolescence can

be further confounded by neglect and abuse. Although

neglect occurs 10 to 15 times more often than abuse,

more than 12 million children are involved in abuse.

Twenty percent of physically abused children are permanently injured, and 1,200 deaths occur each year 

in the United States as a result of abuse and neglect.

Adolescents, who are in the process of trying to figure

out who they are anyway, can experience very low 

self esteem if neglected and can be severely psychologically traumatized by sexual abuse.

Rape and incest are devastating. These hostile 

and dehumanizing events can have lasting effects on

adolescents’ self worth and identity. If rape is a teenager’s first sexual experience, future sexual adjustment

can be threatened. Twenty percent of women under 

18 years who presented at an STD clinic had a violent

sexual experience, 75 percent of girls 14 and under

had a coercive sexual experience, and 62 percent of

girls 16 and under had a violent sexual encounter.

Rape victims have rapid mood swings; feel alternately

degraded, angry, guilty, and helpless; and may have

nightmares and trouble sleeping. Relationships with

peers and consenting sex partners may suffer. The 

victim, out of fear of the attacker, may withdraw and

develop ritualistic behaviors as a defense. Incest victims

often do not report the incest because of fear of disrupting family structure; therefore, the incest may

occur repeatedly over a long period of time. Of growing

concern is the fact that many perpetrators of rape and

incest against adolescent girls are much older men.

Drug Use and Addiction

Use of illegal drugs by U.S. teenagers increased

sharply during the 1960s and 1970s. The increased use

has subsided somewhat; however, of greater concern is

the decreasing age at which adolescents are beginning

to experiment with drugs. Today, two-thirds of all teenagers have tried marijuana at least once before finishing

high school, with some experimenting in grade school.

Treatment for drug abuse and addiction has traditionally

focused on adults, with few programs admitting anyone

under the age of 18. Human developmental differences

have rarely been identified and examined to determine

how they might enhance or adversely affect the process

or outcome of treatment.

Death

Three-quarters of all deaths among teenagers are

the result of accidents, murder, and suicide; accidents,

particularly car accidents, are the leading cause of adolescent deaths. The teen death rate is increasing due 

to violent deaths, although the death rate in other age

groups is stable or declining. Factors that raise the risk

of death in adolescents include drug abuse, poverty,

stressful family situations, and risk-taking behavior.

Suicide is the third leading cause of death among

teenagers. Approximately 500,000 teenagers survive

suicide attempts each year. Most adolescents who

attempt suicide are depressed, but many others 

attempt suicide because of a specific event such as 

the breakup of a relationship, the death of a friend 

or family member, psychological problems within 

the family, chronic physical illness, drug abuse, or

physical or sexual abuse.
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Dentition

The oral cavity is undergoing change during adolescence. During this time, the presence of caries and

gingivitis is highest. Adolescents experiment with sex,

smoking, and drugs, all of which have manifestations

in the oral cavity, on the mucosa, and on the tongue.

PROGRESS SINCE 

ESTABLISHMENT 

OF ORWH

The 1991 Hunt Valley report contained a number 

of recommendations for research that should help 

provide understanding of the changes that take place

during adolescence:

Hunt Valley 1991 Recommendations

Developmental Issues

• Parameters of optimal physical functioning — that

is, exercise capacity — should be outlined to gain 

a better understanding of young women’s full biologic potential. Optimal limits may vary by ethnicity,

body habitus, pubertal staging, or other parameters.

• Studies should investigate the effects of pregnancy,

childbirth, rearing of children, and abortions on

subsequent development, since many adolescents

have these experiences.

Wellness and Risk-taking Behavior

• Studies should look into strategies for teaching

adolescent females responsible health behaviors

that encourage beneficial decisionmaking.

• Research is needed to understand the interaction

among biological, psychological, and social factors

that lead to harmful behaviors, such as early and unprotected sexual activity, use of harmful substances

(especially cigarette smoking and the use of alcohol), and risky behaviors such as reckless driving.

• Research is needed to find out whether there are

developmental factors that play a role in whether

women will adopt a proper diet. There is evidence

that cancer risks can be reduced twice as much in

women as in men by adherence to a low-fat diet.

• Prospective longitudinal studies are needed to

determine the short- and long-term consequences

of sexually transmitted diseases, including infection with human immunodeficiency virus, human

papilloma virus, and chlamydia, as well as pelvic

inflammatory disease.

• Investigations should examine whether multiple

sources of stress affect risk-taking behaviors and, 

in contrast, which factors render girls more

resilient to stress.

• Investigations should analyze the impact of behavioral patterns on women’s health and how individuals with these disturbances respond to disease.

• Research is needed on the relationships among

exercise, body composition, nutrient intake, menstrual function, and osteoporosis in young women.

Mental Health

• Because rates of depression for girls rise after the

onset of adolescence, an emphasis on the biological

and psychosocial mechanisms that make women

more vulnerable should be studied, and the 

importance of choosing appropriate treatment

approaches should be emphasized.

• Subtypes of depressive illness that have higher 

rates in women, such as rapid cycling disorder,

should be studied.

• Indicators of mental health risk in preadolescent

and early-adolescent girls should be identified.

Such indicators may include poor academic performance, a measure already linked to other

adverse health outcomes.

• Research is needed to clarify the patterns and

mechanisms of substance use by adolescent

females, specifically, nonuse, experimentation,

heavy use, and addiction. The influence of gender
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

roles and relationships with male partners should

receive special attention in these studies.

• Studies should explore the link between high-risk

behavior patterns — such as addictive behaviors and

eating disorders — to neurobiologic abnormalities.

• Research is needed on the factors that either protect girls from, or increase their risk for, suicide

gestures. These should include studies examining

the nature of the linkages among suicide and drug

use, depression, and eating disorders.

Injury

• Further study needs to be conducted on the 

risk-related behaviors that render young women

more vulnerable to intentional and unintentional

injuries. According to recent data, the impact 

of sexual abuse and molestation on subsequent 

psychosocial development (both sexual and 

nonsexual) has implications for significant 

numbers of young women.

Special Issues

• It is crucial that valid and reliable measures of

behavior be developed for different ethnic and 

age groups. Such instruments can facilitate understanding of certain topics in behavioral research.

• Studies also should determine reliable and valid

indicators, measures, and screening techniques 

for assessing the general health status of girls 

and young women at all stages of development.

• Longitudinal research is needed to follow the

course of females through their entire life cycle.

Studies of young girls should follow a cohort 

for several years or decades.

• Studies are needed that focus on within-gender 

differences, as well as male-female differences.

• Research should define normal health for girls 

from birth through young adulthood.

PROGRESS

These recommendations are ambitious and,

although they have not been met completely as yet,

successes have occurred during the 6 1/2 years since 

the Hunt Valley meeting in 1991.

• Diagnosis of STDs. Methods for diagnosing sexually

transmitted diseases have improved. Embarrassing

pelvic exams are no longer necessary to detect

STDs like chlamydia.

• CDC Survey of Health Behaviors. The CDC Survey

looks at adolescents cross-sectionally and across

risks to document comorbidity and how concurrent illnesses manifest differently in boys and girls

from 10 to 20 years of age. Agencies are beginning

to study the patterns of behavior of both boys and

girls. In the survey conducted by the CDC, it was

revealed that boys are smoking and drinking less

than in the past, but that more adolescent girls 

are beginning to smoke and drink.

• Environmental impact on female health. The impact

of the environment on health has been well established; however, the particular impact of environmental pollutants on women’s health, in the past,

had not been the focus of research. Now, however,

animal models are being used in studies to determine the effect of pesticides on girls. Scientists are

beginning to look at the long-term impact of toxic

chemicals on girls’ health and reproduction.

• Validation of diversity. The tremendous diversity

among adolescents is being increasingly recognized. Differences between sexes, race, and culture

— and from one individual to another within

sexes, races, and cultures — are beginning to 

be determined to bring greater understanding 

to health issues.

• Improved access to health care. Changes in schoolbased health programs have occurred, improving

adolescents’ access to health care.
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VOLUME 5

• Increased continuity of research. A change in the

focus in HIV has occurred. Women, who were 

previously viewed simply as vectors of the disease,

are now being seen as having the disease with 

their own set of associated complications.

• Reducing teen pregnancy. According to the CDC, 

the overall rate of teen pregnancy in the United

States is decreasing, with some State and locality

rates increasing, some decreasing, and some

remaining constant.

GAPS IN KNOWLEDGE

Adolescence is a time of life charged with

upheaval. Although the outcomes of adolescent development are clearly visible, the mechanisms that bring

about those outcomes remain obscure, primarily

because adolescents have not been studied and have

not been included in clinical trials. Although we know

what happens during adolescence, we do not know

why it happens. This working group believes that 

the following gaps in knowledge exist:

Biological Markers

Little specific research has been conducted to

determine the biological markers across the adolescent

age range. What are the differences among races? What

are the differences between younger adolescents and

older adolescents? What are the differences between

boys and girls? Measurements are based on adult 

measures; adult norms are not tailored to the actual 

age, sex, race, and culture of the adolescent.

Mechanisms of Puberty and Development of 

Environmental Variables

Why does menarche begin earlier in AfricanAmerican girls than in Caucasian girls? Does early 

start of menarche encourage African-American girls 

to associate with, and therefore imitate the behavior 

of, older girls?

No information exists on why two children 

in the same family turn out so differently. Why 

can one cope with difficulties and one cannot? 

Are there genetic, but no biological, differences? 

Adolescents do not feel safe because of widespread

violence, including abductions. How do adolescents

cope with loss of a loved one whether the loss is due 

to violence, accidents, or the normal changes of the 

life cycle?

Immunology of Women During the Life Cycle

Certain diseases are more common in adolescent

teen girls. Is immunology distinctive for teen women?

Do age differences in immunology exist?

Gender-specific Diseases of Adolescence

Do differences exist in how families respond to

acute illness in boys versus girls during teen years?

Why is asthma more common in young boys, but 

at puberty more girls have asthma? Is epilepsy more

acute during teen years? Does chronic disease encourage adolescent girls to take greater risks? Does chronic

illness encourage teens to develop coping skills faster

than teens who are not chronically ill?

Normative Sexual Health

What are the normal sexual behaviors of adolescent girls? When do girls normally make their sexual

debut? Research needs to be conducted to establish

normal physiological development patterns, such 

as when does menarche start and when does breast 

development begin.

Health Outcomes of Risk Behavior

There is an accumulation of evidence that women

are becoming more violent; girls are becoming violent

as young as 14 years of age and the number of female

gang members is increasing. Research needs to be conducted to find out why women are becoming more violent. Also, boys who are violent get caught earlier and,

therefore, get treatment earlier. Girls are in far greater

trouble than boys before they get caught or noticed.

Why are violent girls not identified and treated earlier?
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

Diet and Nutrition

Adolescent eating behaviors are generally poor.

How can strategies for healthy eating be translated to

adolescents? This is particularly critical because many

of the chronic diseases of adulthood begin with eating

habits in childhood, e.g., osteoporosis and heart disease.

Body Image

Research needs to be conducted to describe the

impact of body image choices adolescent girls make

and how these choices affect them in adulthood. For

example, what are the long-term effects of bulimia 

and anorexia on the body? How does striving to

acquire a particular body type affect behavior?

Influences of Culture on Self Concept and 

Disease Outcomes

Many African-American girls straighten their hair. 

If they use too much chemical hair straightener, dermatological conditions of the scalp and face can result.

Use of products to change skin or hair texture can

cause bodily damage that, in turn, can affect behavior

and health habits.

Adolescents develop their self concept during

puberty. Some chronic conditions in African-American

girls are the result of making poor decisions during

puberty. Research needs do be conducted to identify

cultural influences in self concept and disease outcomes.

RESEARCH 

RECOMMENDATIONS

During adolescence, every part of young women’s

lives are in flux. Cognitive, social, and mental health

issues change in response to and in concert with 

the biological changes. Although great diversity in

race/culture and age/gender exists among adolescent

women, few norms have been established, little tracking of growth and development has been completed,

and only a small amount of information has been 

collected. This working group makes the following

research recommendations:

• Conduct a longitudinal study of a national cohort

including common measures and youngsters 

from a wide variety of ethnic/racial, economic, 

specific-risk, and regional groups and subgroups.

What are the common outcomes in this age group

and how do they get there?

• No comprehensive guidelines exist for adolescent

participation in clinical trials. The Society for Adolescent Medicine does have a statement of consent.

The working group reaffirms support to adolescents as minors, but they must be allowed to 

participate in studies and to receive treatment.

• Because no guidelines exist for adolescent participation in clinical trials, NIH should be urged to

convene a workshop to study the barriers and facilitators to adolescent research, including current

guidelines, IRB approvals, and ethical and legal

issues for gathering data from this age group.

• Alternatively, NIH might commission the Institute

of Medicine to conduct an assessment of the legal,

moral, and ethical issues involved in conducting

clinical research in the adolescent population. The

precedent for this assessment is in a previous Institute of Medicine report on the issues involved in

including women in clinical studies (Women and

Health Research. Washington, D.C.: Institute of

Medicine, 1994).

OTHER ISSUES TO 

BE EXPLORED AND 

ELUCIDATED

Development Issues Across the Adolescent Years

• Biological development. How does biology affect

behavior? How does the immune system change

body composition and affect behavior?

• Social development—how does body development

affect social behavior?

• Psychosocial development.
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VOLUME 5

• Environmental effects—how does the environment

affect body composition and development?

• Cognitive development.

• Mental health.

Risk-taking Behaviors

• Sexual behavior. Primary and secondary prevention

of pregnancy. What are the implications for STDs

and pregnancy? (The best prevention for STDs 

may not be the best prevention for pregnancy.) 

Difficult questions, such as what are girls’ masturbation habits, need to be addressed. What is the 

role of coercion in an adolescent girl’s sexual

debut? What is the age of the sex partner and 

how does that affect development? Male-female

dynamics need to be examined.

• Substance use and abuse.

• Others: violence, injury, suicide, runaways, 

and homelessness among teens. Conduct a 

cross-sectional study of girls in gangs versus 

girls not in gangs.

Promoting Healthy Behaviors

• Nutrition. How can healthy eating habits be 

communicated to adolescents?

• Physical Activity. How can adolescent girls be

encouraged to get regular exercise to prevent 

obesity? How do we promote healthy behaviors 

like delaying smoking, alcohol, and sex?

• Sexual health and hygiene.

• Oral health.

• Effective/accessible, user-friendly screening tools.

Adolescent Participation in Research

• Normed assessment tools must be developed.

• IRB issues around adolescent consent need 

to be explored.

• Diversity.

• Inclusion in clinical trials.

• Support of secondary analyses.

• Supplements for ongoing studies.

Coping Skills

• Chronic disease.

• Family issues. Teach parenting skills to teens.

• Life events.

• Violence.

• Resilience. What are the skills needed to 

deal with emotions like anger?

Communication

• Teach provider communication skills.

• Develop age/culturally appropriate sexual 

information.

• Examine and utilize channels and models 

of communication, i.e., providers, parents, 

teachers, media, and peers.

REPRODUCTIVE AND

MIDDLE YEARS

BACKGROUND

The past 6 years have brought tremendous

advances in women’s health research for

women in the reproductive and middle years,

especially with recognition that health needs of women

in this age group go beyond reproductive issues. The

1991 Hunt Valley Report focused on issues of sexually

transmitted diseases (STDs), reproductive morbidity,

injuries, malignancies, and cardiovascular diseases,

along with the major themes of racial and ethnic 

issues, biobehavioral issues, and social context. 

SCIENTIFIC PROGRESS

According to a recent paper,1 during the past 2

decades research in women’s health has experienced

unprecedented growth. Women’s health is no longer

limited to diseases of the reproductive organs, and

research in women’s health derives from social, economic, legal, political, and environmental factors. 

The group refers to the paper by LaRosa and Alexander for a more comprehensive discussion of the

advances in women’s health since 1991.

GAPS IN KNOWLEDGE

Sexual Reproductive Health

As recognized in the 1991 Hunt Valley report,

because these years are the reproductive years, a

woman’s well being, productivity, and personal development depend largely on “her ability to live free of

morbidity in terms of sexual function, fertility, pregnancy, and delivery.”2 Therefore, issues in sexual 

reproductive health continue to warrant research. 

Two areas specifically require additional research: 

prevention of sexually transmitted diseases (including HIV) and use of effective contraceptives.

Prevention of Sexually Transmitted Diseases

Sexually transmitted diseases (STDs), and especially HIV, are still epidemic in this age group. The

Centers for Disease Control and Prevention (CDC)

reports that incidence of HIV in women is increasing 

at a rate four times that of men. It is a leading cause 

of morbidity and mortality in reproductive-aged

women and especially of minority women.

Among the approximately 50 diseases that can be

transmitted sexually, the most common are chlamydia,

genital warts, genital herpes, gonorrhea, pelvic inflammatory disease, and syphilis. Because of the asymptomatic nature of many conditions in the female body,

there is no effective screening mechanism and, often,

symptoms either do not appear or appear only after 

the disease is quite progressed. Additionally, the social

stigma of STDs prevent many women from seeking

treatment. The untreated diseases advance, affecting

surrounding and related systems. Consequently, the

morbidity associated with STDs has a profound impact

on women’s fertility and gynecologic health, and also

neonatal health. The long-term consequences of

untreated STDs in women include increased risks 

for cervical and vulvular cancers, infertility, tubal 

Cochairs

Linda Alexander, Ph.D.

United Information Systems, Inc.

Gwen W. Collman, Ph.D.

National Institute of Environmental Health Sciences

National Institutes of Health

Gloria Richard-Davis, M.D.

Tulane University Medical Center

Rapporteur: Angela Lorio

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pregnancy, miscarriage, premature delivery, stillbirth,

and pelvic inflammatory disease. In infants born to

mothers who have or have had STDs in the past, complications include infant pneumonia, conjunctivitis,

genital herpes, birth defects, blindness, and death.

Contraceptives

Contraceptive development in the United States

has slowed appreciably during the past two decades,

while researchers outside of the United States are continuing to work on improving existing methods and

developing new methods of contraception. The AIDS

epidemic has renewed interest in barrier methods to

help prevent the spread of sexually transmitted diseases. Female-controlled barrier methods and agents

with virucidal and microbicidal properties are needed.

Although there are presently various choices for

contraception available to women and men, there still

remains a high incidence of unwanted pregnancies and

sexually transmitted diseases; clearly, men and women

are still having unprotected sex. There are gaps in the

scientific literature about the decisionmaking processes

of women and men related to choosing and using contraceptives. Research about the psychosocial context in

which women and men choose to use or not use contraceptives is needed to develop feasible contraceptive

options for different populations and circumstances.

Access to Health Care

Managed care, the reduced physical and social

resources of women, changing roles of women, changing demographics, and available communication technologies have changed the way health care and health

information reach women, and how women access

health care. Research is lacking to determine the most

effective ways to reach the full spectrum of women,

using the full potential of resources available.

Changing demographics in the United States indicate that, in the near future, the largest proportionate

increases in the population across all age groups will 

be among Americans of African, Hispanic, Asian, and

Native Indian descent. These groups differ greatly 

in social, political, and economic history; current

socioeconomic status; extent of acculturation; and cultural norms. The diversity in culture and socioeconomic

status and the heterogeneity among and within racial

and ethnic populations must be recognized and considered in the spectrum of women’s health research. 

Growing recognition of the importance of cultural

and ethnic heterogeneity must be channeled into conceptual and theoretical models of care. Methodologies

appropriate to the study of racial and ethnic group 

heterogeneity must be designed to be sensitive and

effective in ethnic minority populations.

Research should explore how to educate providers, with an emphasis on population diversity, its

capabilities and resources, and the need to tailor health

care access and information accordingly. Currently, 

a struggle between the scientific community and the

community it ideally can serve prevents beneficial collaboration to implement effective research initiatives.

We must find ways to implore sensitivity within the

scientific community to the need for community

involvement in every phase of the research agenda.

Environmental Issues

Environmental exposures and the effects on

women’s health involve physical and chemical exposures (e.g., pollutants, chemicals, adverse weather 

conditions, structural and ergonomic designs) as well 

as exposures associated with the social environment

(e.g., economic status, education, culture, residence,

and view of self concept) that predispose women to

stresses and other morbidity and mortality factors.

These exposures affect every aspect of women’s diverse

roles — as homemakers, as spouses, as care givers, 

and as employees in the workforce.

We need to know more about hormonal disrupters in the home and the workplace. Injuries still

account for a significant number of deaths and longterm morbidity of women in this age group. More

effective gender-specific research regarding accident

impact and prevention is needed; for example, 

car-crash tests simply use a smaller male model to

determine the effects of impact on the female body.
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Inclusion of Pregnant Women in Clinical Studies

Although more women have been involved in 

clinical trials, special populations of women, especially

pregnant women, are not being studied. The inclusion

of pregnant women in clinical trials presents a serious

ethical dilemma. While knowledge about the effects of

drugs and interventions in this population is clearly

needed, there are unknown implications for the pregnancy, the health of the fetus, and the long-term health

of the child. For example, children of mothers who

used diethylstilbestrol (DES) to prevent miscarriage

during their pregnancies have serious disorders of the

reproductive, endocrine, immune, cardiovascular, and

skeletal systems; these disorders are now, 25 years later,

identified as transgenerational effects of the drug.

In 1993, the FDA revised its 16-year policy prohibiting the inclusion of women of childbearing age 

|in Phase I and II clinical trials and stipulated genderspecific analysis of new drugs in development. However, pregnant women are still not allowed in studies

other than those directly addressing pregnancy issues,

and most internal review boards still request the exclusion of pregnant women and the use of adequate birth

control during clinical trials. The FDA statement

declares that pregnant women can be included in 

clinical trials, not necessarily that they should be.

We need to establish a clear definition of all 

issues surrounding pregnancy and clinical trials 

and to establish parameters for inclusion of pregnant women in clinical trials.

Alternative (Complementary) Medicine

Women in their reproductive and middle years 

are using “alternative therapies” in increasing numbers.

According to a survey by researchers at the Harvard

Medical School, about one-third of all U.S. adults rely

to some extent on nontraditional methods of treating

illness.3 These alternative therapies include the use 

of vitamins and herbs, acupuncture, massage therapy,

hypnosis, chiropractic treatment, and pastoral and

church-based mental health care. Patients are asking

their physicians about the effectiveness and safety of

these therapies; however, little is known about the

effects and interactions with medically supervised

interventions that patients may be undergoing concurrently. Little is known about the population that

seeks such alternative treatments.

The medical community must recognize alternative medicine and treat it as a valid form of therapy, if

only because of its broad use. Like medical treatments,

alternative therapies should undergo scientific review

by using clinical studies that compile data regarding

the population that uses them, overall effectiveness 

and failure patterns, long-term effects, and clinical

caveats. Finally, the medical community must recognize

the already-occurring shift from the concept of “alternative” medicine to that of “complementary” medicine.

CHANGE IN QUESTIONS

SINCE HUNT VALLEY

In the reproductive and middle years, there are

recurring themes of existing voids, important issues,

and recommendations for future initiatives for research 

in women’s health. Each research recommendation

should be examined through a filter of the following

four themes.

Treating Women Globally

We must treat the population globally, recognizing

the effects of medicine and interventions over the life

span of the woman and considering not only women

and men as diverse, but women as part of a diverse

and nonhomogeneous group. Research within various

social, ethnic, racial, and cultural groups of women

should be approached in the same manner as genderspecific research. The diversity among these groups

necessitates that education, treatment, prevention, 

and access programs be tailored accordingly.

Recognizing the Holistic Nature of Disease 

States and Conditions

A holistic approach is necessary to the study of

interventions and disease states. Diseases do not exist 

in a vacuum; the mind-body connection must be 
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

recognized and explored. For example, women who

were victims of sexual abuse or who suffered the threat

of sexual abuse are more likely to have irritable bowel

syndrome, which can cause gallbladder disease. Likewise, these women are vulnerable to substance abuse

and risk-taking behavior, which increases their chances

of contracting HIV or other STDs. These diseases, if left

untreated, can cause subfertility, complicated pregnancies and birth, and cancer. Long-term, delayed, and

transgenerational effects of drugs and other treatments

must be considered as they relate to the incidence and

risk of subsequent diseases.

Holistic research efforts should consider specific

health endpoints that affect women in the middle 

years to the greatest degree. The following conditions 

or disease states should be given high priority: autoimmune diseases; cardiovascular diseases; DES exposure;

endometriosis, infertility, and uterine fibrosis; female

cancers; infertility; mental health diseases such as

depression, panic disorder, and Posttraumatic stress

disorder; STDs; stress-related gastrointestinal disorders;

pregnancy; substance abuse; and urinary incontinence.

Empowerment of the Community

Research in women’s health needs to re-establish

the empowerment of the community, with an emphasis

on information from the constituency. So that science

can fit the needs of the community, research should 

be conceived, conducted, and followed through using

partnerships among consumers and patients, scientists,

clinicians, and federal agencies. Focus groups should

involve participation of the consumer/patient, with 

special consideration to minority groups.

Enlightened Providers

Research efforts should encourage the development of enlightened providers who are sensitive to 

the social, psychological, and behavioral connections 

to physical ailments and who should be trained to disregard previous stigmas associated with the diagnoses.

Providers need to understand the cultural, ethnic, and

social communities in which women live, considering

the resources, education levels, perceived safety factors, and social mores that affect women’s ability and 

inclination to access health care. For example, several

studies of and programs to deal with violence against

women have been initiated to improve outreach and

assistance. The most successful efforts have partnered

with community efforts to assist victims and have

focused on training health care professionals to 

recognize signs of violence.1

RECOMMENDATIONS 

AND CONCLUSIONS

Sexual Reproductive Health

Research needs to approach the prevention, 

diagnosis, and treatment of STDs with an emphasis 

on utility, effectiveness, availability, and education 

in the diverse populations of women.

• Research the causes of STDs emphasizing the 

holistic approach, investigating the hormonal and

immunologic influences on susceptibility to these

diseases and the relation of risk-taking behavior,

substance abuse, and other behaviors and disorders commonly associated with the diseases.

• Research decisionmaking and compliance factors 

of contraceptive use to develop contraceptive

options tailored to different circumstances and 

different populations.

• Continue research of gender-sensitive prevention,

diagnostics, treatment, and outreach efforts for

STDs, with special emphasis on pregnant women.

• Develop less expensive, faster diagnostics and 

treatments for STDs.

• Develop topical microbicides that are nonirritating

and effective against resistance.

• Develop research on a male contraceptive.

• Develop more female-controlled barrier contraceptive methods.
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VOLUME 5

Access to Health Care

Recommendations in this category focus on efforts

that will bring science closer to the people it serves,

lifting barriers among scientists and clinicians and the

public and encouraging these groups to collaborate.

• Develop models of comprehensive services across

the life span of women, with research regarding

basic biologic systems to educate providers.

• Develop a gender-specific model of information

and communication that responds to the manner

in which diverse groups of women receive and

process information — utilize grassroots efforts,

print and television media, telemedicine, the 

Internet, and distance learning.

• Develop successful models of outreach to special

populations, such as minorities and inhabitants 

of transitional housing (e.g., prisons and homeless shelters).

• Conduct epidemiologic studies to define the

diverse populations and their distinct health 

care needs.

• Incorporate and, through followup, evaluate 

constituent participation in all facets of research

targeting women. Emphasize partnerships among

consumers, clinicians, and scientists and coordination among federal agencies.

Environmental Exposures

Research on environmental exposures should be

all-inclusive of physical, chemical, atmospheric, and

social exposures that affect women in their various

roles in the home, workplace, and community, and

should also consider transgenerational effects. Special

emphasis should be placed on recognizing the nonhomogeneous nature of women and the holistic approach

to clinical study. Specific recommendations focus on

prevalence and etiologic factors to help identify treatments and interventions.

• Identify hormonal disrupters, especially in the

home and workplace.

• Examine gender differences in the effects of hormonal disrupters, especially in the workplace.

• Examine eco-estrogens and the subsequent influence on development of benign and malignant

tumors and the disruption of hormonal regulation.

• Continue to examine transgenerational effects 

associated with physical and social environmental exposures.

• Assess structural design and ergonomic issues, considering the unique features of the female body.

Inclusion of Pregnant Women in Clinical Studies

Research involving pregnant women, and women 

of reproduction potential, in formal clinical trials requires careful thought and planning, with consideration

to transgenerational effects and the effects of interventions on the existing pregnancy and fetus. Not all data

needs to be collected on the gargantuan level, and

opportunities for data collection are presently available.

For example, women who use drugs and alternative

therapies during pregnancy without the supervision 

of physicians or clinical investigators present an 

opportunity for passive data collection. Additionally, 

collection of followup data on subsequent pregnancies and children can be explored, using women 

who have participated in previous clinical trials.

Recommendations involve finding the group of

women from which data can presently be obtained,

establishing from whom and in which situations pregnant women can and cannot be involved in research,

and considering women of reproductive potential 

when planning clinical studies and followup. Pregnant women and women of childbearing age should 

be included all studies, not just those directly 

addressing pregnancy issues.

• Recognize and use opportunities to collect passive

data to study the effects of drug use on pregnancy.
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

• Include the investigation of effects of medical 

interventions in women of reproductive potential 

in existing clinical trials and follows.

• Study interactions of prior drug use and medical

intervention on conception and pregnancy.

• Sponsor a conference to establish a consensus 

to approach the inclusion of pregnant women 

in clinical studies, recognizing that careful, 

long-term thought and planning are necessary.

• Define and find cohorts of pregnant women that

can be enrolled in clinical studies, including studies not directly related to pregnancy issues.

• Establish when Phase I and Phase II trials are

appropriate for inclusion of pregnant women, even

trials not directly related to pregnancy issues.

Alternative (Complementary) Medicine

Because so many women are using alternative

medicine, the medical community must acknowledge

and accept these therapies as valid forms of medical

intervention and must approach the study of their use

accordingly. Accepting these therapies as complementary, rather than alternative, medicine is needed.

• Conduct epidemiologic studies to establish 

the prevalence and existence of the use of 

alternative therapies.

• Use social and behavioral studies to ascertain 

consumption patterns and understand the 

appeal of alternative therapies.

• Conduct Phase I, II, III, and IV clinical trials to

determine the effectiveness, safety, and complications/adverse effects of alternative therapies.

• Increase provider awareness and education 

regarding alternative therapies so patients can 

make informed decisions regarding their use.

ENDPOINT 

DISEASE—STATES 

OF HIGH PRIORITY

Autoimmune Disorders

• Increase research to clarify how the female immune

system functions and how those functions change

over the course of the menstrual cycle and during

pregnancy, and the influence of environmental 

factors on those functions.

Cardiovascular Diseases

• Increase research on the basic mechanisms 

of reproductive hormones in cardiovascular 

disease states.

• Increase gender-specific clinical trials to identify

female-specific risk factors and pharmacokinetics.

Depressive and Mental Health Disorders

• Increase research on hormonal, behavioral, 

and genetic factors predisposing women to 

these disorders.

• Identify gender-specific pharmacokinetics.

DES Exposure

• Continue research to determine the effects of 

second-generation exposure to diethylstilbestrol

(DES), with special attention on its effects on 

fertility drugs, use of hormone replacement 

therapy during menopause, risk and incidence 

of female cancers, and risk of transmission 

to a third generation.

Endometriosis, Infertility, and Uterine Fibrosis

• Increase basic molecular/cellular regulation

research with specific attention to defining 

the basic biology of these diseases and to 

identify components of their causes.

• Increase well-designed clinical research.
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VOLUME 5

Female Cancers

• Particularly for breast, lung, and ovarian cancers,

increase research initiatives for finding early markers for detection, gene and molecular therapy, environmental impact, risk factors, and modification.

Infertility and Fertility Control

• Develop more cost-effective treatments for ovulation induction.

• Increase understanding of fertilization and implantation, ovulatory disrupters, and male infertility.

Obesity

• Increase research initiatives in the basic understanding of genetic, behavioral, and environmental

factors in obesity.

Polycystic Ovarian Syndrome

• Increase research on androgen impact on CVD 

and the insulin resistance mechanism.

Stress-related Gastrointestinal Disorders

• Educate and sensitize the medical community about

early and/or preventive diagnosis of gastrointestinal

disease in women, with special consideration of the

brain-gut connection linking abuse, stress, anxiety,

and panic disorder to gastrointestinal diseases.

• Implement existing technology and procedures to

establish early diagnosis of symptomatic patients 

in order to define groups that will benefit most

from early intervention and treatment modalities.

• Establish a safe therapeutic environment to deal

directly with issues of safety in the clinical setting

for women who perceive threats in the environment (e.g., use draping equipment and attune 

to background noise).

Substance Abuse

• Conduct basic, epidemiologic, and longitudinal

research to identify gender differences in the 

causes, consequences, risks factors, and preventive factors of drug use, abuse, and dependence.

• Develop effective drug abuse treatment and prevention models that are specific to the unique

needs of women, with consideration to the impact

of co-existing factors such as violence, victimization, and psychiatric disorders.

REFERENCES

1 LaRosa J.H., Alexander L.L. Women’s Health Research.

Ottawa, Canada: Women’s Health Forum Sante des

Femmes. August 8-10, 1996. U.S. Public Health Service’s

Office on Women’s Health, U.S. Department of Health

and Human Services.

2 Report of the National Institutes of Health: Opportunities

for Research on Women’s Health. Hunt Valley, MD: September 4-6, 1991. Office of Research on Women’s Health,

Office of the Director, National Institutes of Health. 

3 Alternative Medicine. Harvard Women’s Health Watch, 

June 1994. Boston, MA: Harvard Medical School 

Health Publications Group, 1994.

PERIMENOPAUSAL AND

POSTMENOPAUSAL YEARS

BACKGROUND

I

n the 1991 report of the National Institutes of

Health on opportunities for research on women’s

health, the Life Span Working Group on the perimenopausal to mature years delineated the major public health concerns facing women during this segment

of their lives and issued a series of recommendations

for research initiatives.

Since that time several important large-scale

research programs have begun to examine issues

important to the health of women in their peri- and

postmenopausal years. The Women’s Health Initiative

(WHI) is a 15-year program begun in 1991 and scheduled for completion in 2007. It includes clinical trials,

observational studies, and a community prevention

program involving more than 164,000 women in all

phases. The clinical trials are focused on studies of 

the effects of conjugated equine estrogen on coronary

disease and breast cancer, diet modifications on breast

and colon cancer, and calcium and vitamin D on osteoporosis and fractures. An ancillary study on Alzheimer’s

disease will evaluate 8,000 of the women participating

in the hormone replacement therapy trials for changes

in memory. The observational study is aimed at identifying biomarkers and risk factors in women who are

participating in a variety of hormone replacement 

therapies. The community prevention program (with

support by the Centers for Disease Control and Prevention) has components devoted to improving behaviors,

using lifestyle modifications in diet, exercise, and

smoking cessation that have an impact on women’s

health, and to assessing attitudes of minority women

toward surgical menopause (hysterectomy and

oophorectomy).

NIH is also sponsoring the first large-scale national

study to examine the health of women in their 40s and

50s. Based at seven research centers across the United

States, the Study of Women’s Health Across the Nation

is designed to track the health of approximately 3,000

women during the transitional years of middle age,

examining the physical, psychological, and social

changes that take place at the midlife and as women

approach and traverse the menopause. A special feature

of this study is the inclusion of a large proportion of

African Americans, Hispanics, and Asian Americans 

of Chinese and Japanese descent.

The 1991 Hunt Valley report identified a number

of priorities for research in key areas affecting the health

of women in their peri- and postmenopausal years. In

the years since that report was prepared, a number of

these issues have been addressed. However, four of the

1991 research priorities have yet to be fully explored

and continue to be of utmost importance:

1. Studies should examine the transition from premenopausal to postmenopausal status, including

the changes that occur in endogenous estrogen 

levels and in hormones other than estrogen.

Cochairs

Anuradha V. Rao, M.D.

Tulane University Medical Center

Sherry Sherman, Ph.D.

National Institute on Aging 

National Institutes of Health

Sarah Moody Thomas, Ph.D.

Louisiana State University Medical Center

Rapporteur: Miriam Y. Miller

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

2. Studies should elucidate the mechanisms by which

estrogen, progestin, growth factors, androgens, and

neuropeptides may induce cell transformations and

promote tumor growth.

3. Studies should assess the effects of early menopause

(whether chemically, surgically, or disease induced)

in breast cancer survivors, as well as the effects 

of hormone therapy in this group. Of particular

importance is the effect of hormone therapy 

on recurrence of breast cancer, development 

of heart disease, and quality of life.

4. Studies should identify successful interventions 

for long-term weight management, including 

interventions to increase physical activity levels.

RESEARCH 

RECOMMENDATIONS

Since the Hunt Valley report of 1991, efforts 

have been made to include individuals from diverse

ethnic and cultural backgrounds in clinical trials and

observational studies. The basic premise of research 

on women’s health is that it must be studied and

understood in the context of culture, ethnicity, and

socioeconomic status for research in all areas of periand postmenopause; all research hypotheses should

start with ethnic-specific criteria. More specific research

priorities in the area of peri- and postmenopause fall

into three broad categories: the process of the menopausal transition, pharmacological aspects of peri- and

postmenopause, and behavioral and psychosocial

aspects of peri- and postmenopause.

The Menopausal Process

Since the natural history of menopause and 

the processes underlying the transition from pre- to

postmenopause are not as yet well understood and

since an understanding of these processes is critical 

to provide the foundation for further research into

women’s health in the postmenopausal years, studies

should be undertaken to fully explore the process 

of transition from premenopause to perimenopause 

to postmenopause.

• Work should be undertaken to clarify and 

define the various stages comprising the transition from premenopause to perimenopause 

to postmenopause.

• Studies should characterize the normal antecedents

and sequelae of the menopause transition and, in

so doing, distinguish this stage of the female life

cycle from disease processes and the processes of

aging. Specific areas of opportunity should also

include bleeding abnormalities, the development 

of obesity in the menopausal years, and the role of

the postmenopausal ovary on the manifestation of

menopausal symptoms subsequent to morbidity.

• Research should be conducted to evaluate the

effects of surgical versus spontaneous menopause

on morbidity and mortality and on factors related

to women’s sexuality. Hysterectomy and the factors

affecting it should be emphasized in the research

agenda. Areas of investigation should include

fibroids and their treatment, hormonal aberrations,

physician and patient preferences, analysis of the

outcomes of hysterectomy (with and without

oophorectomy), and alternatives to hysterectomy

(e.g., pharmacological and less-radical surgical

approaches).

• Additional aspects to explore include environmental, cultural, and lifestyle influences on menopause.

Questions to be addressed include: What constitutes optimal primary care for women in this stage

of life? What are the effects of physician training 

on the health care of menopausal women? Would

women be better served if gynecology were separated from obstetrics as a field of specialization?

What are women’s needs and what are appropriate

strategies for contraception during the perimenopause? What is the influence of environmental

agents on estrogen receptors?
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VOLUME 5

Pharmacological Aspects of Peri- and Postmenopause

• The effects of endogenous and exogenous hormones on tissues and physiological processes 

of multiple target organs should be evaluated.

• Studies of hormone replacement therapy (HRT)

should be continued and expanded. Specific areas

to be explored include the effects of administering

conjugated versus pure forms of estrogen, natural

versus synthetic progestins (for women with a

uterus), the route of administration (oral versus

transdermal), the schedule in estrogen-progestin

regimens (sequential versus combined-continuous),

methods of reducing side effects and optimizing/

individualizing regimens for patients, factors affecting pharmacokinetics (such as lifestyle, smoking,

obesity, and diet and other ingested substances),

and the effects of HRT on cardiovascular disease

from the viewpoint of primary and secondary 

prevention (including CABG, angioplasty, and

adjunctive devices).

• Research should be implemented on alternatives 

to HRT, including pharmacological agents such as

Raloxifene and other selective estrogen receptor

modulators (SERMS), diet and dietary supplements (for example, phytoestrogens), behavioral

interventions, and the role of testosterone.

Behavioral and Psychosocial Aspects of 

Peri- and Postmenopause

• Studies should be developed to explore the psychological aspects of menopause and the transition to

menopause, including women’s attitudes toward

bleeding and the symptoms of menopause.

• Research should be conducted on the effects of 

caregiving in the menopausal years. Because the

burden of caregiving on menopausal women has

increased due to recent social trends, such women

often find themselves taking care of family members of two or three generations. How does the

stress of this increased burden affect the menopausal process? How do caregiving responsibilities

affect women’s participation in preventive health

practices and clinical trials and other studies?

• Studies should be designed to determine the attitudes, knowledge, and perceptions of women,

health care providers, and society in general toward

menopause and toward the aging processes. What

are the barriers to health care in this period of 

life and how can they be overcome?

• The psychosocial (as well as the biomedical)

aspects of genetic susceptibility testing should 

be explored. These include such issues as appropriate interpretation of data, confidentiality, psychological impact of knowledge of the potential 

for genetic defects, implications for health care,

and insurability.

• Research should be undertaken on the health

effects on menopausal women of such stressors 

as bereavement, abandonment, the “empty-nest”

syndrome, and other forms of loss.

• Strategies and channels for disseminating new

medical and health promotion information to a

variety of audiences (including women, health 

care providers, and society at large) should be

devised and implemented.

In addition to the new initiatives outlined above,

meta-analyses on data from prior studies on weight

management and hysterectomy should be undertaken

to maximize the value of the extensive research that has

already been conducted in this area of women’s health.

ELDERLY AND FRAIL

ELDERLY YEARS

BACKGROUND

The social context of health — including 

religion, ethnicity, and culture — has an

important effect on health behavior, and

research must understand this context. Socioeconomic

status (SES) plays a major determining role in health

status. The United States has the highest poverty rate

for older women among industrialized nations — one

out of four are poor or near poor. Many women slip

into poverty upon the death of their spouses, losing

both income and companionship, and low income is 

a major barrier to health care access for older women.

Although Medicare covers almost 98 percent of the

population (according to an estimate of the U.S. Health

Department), it may cover only one-half of services to

beneficiaries. Co-payments, deductibles, and out-ofpocket expenses present major problems to the elderly

poor, particularly those with chronic conditions.

The health of elderly women is increasingly important because of the rapidly growing numbers of women

in this age category. Progress has been made; for example, the prevalence of disabling conditions has declined

from 24.9 percent to 21.3 percent in the 12-year interval between 1982 and 1994. Nevertheless, women are

at higher risk than men for chronic conditions like

arthritis, osteoporosis, and depression. Arthritis affects

more than half of all women 65 and over. Rates of

activity limitation and disability among women aged 

65 to 74 are 1.5 times those for men. Osteoporosis

increases dramatically with age, affecting more than 

50 percent of women 80 years and older.

RESEARCH 

RECOMMENDATIONS

The following research recommendations use as

their base the holistic definition of health as put forth

by the World Health Organization: physical, social, 

and mental well being.

Social and Behavioral Issues

• Focus on changes in family and social structures.

What implications do the changing social and 

family structures have on women’s health issues —

for example, smaller families, increased numbers of

women in the workplace, and reduced availability

of support systems? What are the economic effects

when women drop out of the workforce to become

care givers when family members, parents, or

spouses become ill? With more women in the

workforce, more services such as advice on health

insurance and retirement and financial planning

should be available to them.

• Focus on the feasibility and intergenerational

impact of formal and informal caregiving: stress,

coping, training lay providers, and respite care.

Caregiving almost always is provided by women

and carries hazards for women’s health. What

stresses are involved and how can these stresses 

Cochairs

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

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Carola Eisenberg, M.D.

Harvard Medical School (Emerita)

W. Lou Glasse, M.S.W.

Older Women’s League 

Veronica J. Scott, M.D., M.P.H.

Meharry Medical College

Rapporteur: Gillian Brown

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

be ameliorated? What configuration of formal,

informal, and respite care can support a family’s

ability to provide long-term care, thereby delaying

both morbidity and placement in a skilled nursing

facility? What are the best methods to educate 

lay providers to care for elderly women? How 

can families be helped to adapt to the structural 

and lifestyle changes required for providing 

elder care at home?

• Promote personal choice and autonomy in living

situations. Low socioeconomic status almost always

shapes the quality of life and the health of elderly

women. How can women be assisted to retain a

sense of autonomy and personhood even when

choices are limited?

• Identify the antecedents and consequences of

mandatory elder-abuse reporting. How can physicians and nurses be educated to increase their

awareness and identification of elder abuse? What

questions should they ask? From experience with

reporting child abuse, what might be the effects of

legislation requiring reporting elder abuse? What

strategies and policies protect against elder abuse?

• Develop ways to empower older women in their

use of health care. How can elderly women be

assisted in their interactions with the health care

system? For example, how can older women be

encouraged to ask for second opinions? Despite 

the increased recognition of the importance of

mammograms and clinical breast examinations, 

too few elderly women are asking for and receiving these services; how can women be educated to

insist on them? How can ethnic and cultural prohibitions against some of these services be overcome?

How can physician performance be monitored?

• Increase efforts in health promotion and disease

prevention. Educate women about risk factors,

causes of increasing disability, and the availability

and importance of immunizations for preventable

illnesses. How can older women be encouraged to

participate in clinical studies, particularly women

in disadvantaged and underserved populations?

How can research results be shared with these

groups of women?

• Encourage research on the impact of managed care

on the health and well being of older women. 

How does managed care impact elderly women,

particularly those with chronic conditions and with

comorbidities? For example, managed care companies often require shorter hospital stays than have

been customary. What impact does this have on

elderly women who live alone and on those who

provide home-based caregiving? How can policy

makers in managed care companies be educated

about research results? How can managed care

companies be encouraged to respond appropriately to the health needs of elderly women?

• Continue research on mobility and safety issues.

Continue researching older women drivers and

pedestrians and how to prevent accidents and 

promote safety.

• Develop research on the use of assistive technologies. The use of assistive devices for augmenting

hearing, vision, and speech loss should be studied 

in home-based, community-based, and institutional settings.

Mental Health Issues

Depression affects many more women than men.

Why does this occur, and why does that gap narrow

among the elderly? Why is the suicide rate among

older men higher than among older women? Why is

there an increase in alcoholism among older women?

• Study gender differences in depression.

• Continue studies of alcoholism and other drug

abuse and dependence, including dependence 

on prescription drugs.

The issues in these two categories relate to some 

of the questions asked in the section on social and
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VOLUME 5

behavioral issues. For example, is the increase in 

alcoholism among older women affected by living 

conditions? By loneliness? By changing family and 

support systems or lack of those supports?

• Study effective coping strategies. What are the 

stresses both for the elderly and frail elderly and 

for their care givers? What mechanisms could 

help both parties cope better? Can more respite

care be provided?

• Investigate dementias. Dementias influence women

directly and as care givers. Why are women at

greater risk than men for dementias? What can 

be done to reduce the toll of dementia? To reduce

the stress for the families? To enhance cognitive

function in the elderly? To educate care givers 

on appropriate modes of care?

• Study the impact of living arrangements on mental

health. What are the effects of facilities that allow

aging-in-place (the movement from independent 

to assisted living and then to nursing care)? What

stresses are caused by the necessity of relocation? 

By loss of independence?

• Study the impact of chronic pain on mental and physical health. As women age they often face comorbidities that can result in chronic pain. How can

this pain and the fear of suffering be relieved?

• Study the impact of fears of death and dying and/or

terminal pain. How do the spiritual beliefs of older

women affect their attitudes toward health and

toward illness and death? Are there special ways

that women prepare for death and dying? What

legal, social, and health care supports should 

be provided?

Physiological Issues

Cardiovascular Illness

Recent understanding of the effect of cardiovascular

illness on women has included greater awareness that

women are treated less aggressively than men. Research

should continue to examine treatments and outcomes

for men and women.

Osteoporosis and Osteoarthritis

These conditions cause significant pain and suffering for older women as well as serious functional

impairment, impacting the quality of women’s daily

lives and producing financial burdens.

• Continue research on the long-term effects of HRT.

• Research interventions to help women 65+ who

have not taken HRT.

• Study alternatives for women 65+ who have 

taken HRT.

• Research methods for delaying frailty.

• Study the impact of musculoskeletal fitness on

comorbid disease progression.

• Research musculoskeletal and cardiovascular

response to exercise.

• Investigate why disability rates are decreasing

among the elderly, and the impact of this decrease.

Urinary Incontinence

Urinary incontinence is a major clinical problem

and a significant cause of disability and dependence 

in older women. In 1995, a U.S. Public Health Service

Task Force on Aging Research stated that urinary

incontinence affects more than 10 million Americans,

approximately 85 percent of whom were women.

• Study normal and abnormal bladder physiology 

in order to suggest treatment for incontinence.

• Research adjunctive treatments, such as pharmacologic therapy.

• Investigate behavioral interventions for persons 

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

• Conduct clinical trials to examine effective therapies for specific types of urinary incontinence.

• Increase educational efforts for health providers 

and patients regarding the effectiveness of 

bladder training.

• Review staff management techniques to ensure

compliance with treatment protocols.

Pain and Its Impact on the Elderly

The recommendation to study the impact of

chronic pain on physical health is repeated here

because of its connection with physiological issues.

More research is needed to find ways to relieve that

chronic pain of comorbid conditions in older women.

Surgery

• Develop strategies to enhance recovery from

surgery in older women, especially from transplants and prosthetic devices.

• Examine criteria for transplant surgery and the 

use of prosthetic devices. Are older women considered appropriate candidates for these devices?

Delaying and Correcting Sensory Impairments 

• Investigate vision impairments in older women,

particularly the increasing problem of macular

degeneration.

• Research hearing loss and its impact on quality 

of life.

Impact of Human Genome Research on Genetic

Basis of Conditions Affecting Longevity

Is there a genetic basis for chronic diseases? Is

there a genetic basis for retention or loss of physical

functioning in old age?

HEALTH PROMOTION

ACTIVITIES 

Health promotion activities should be targeted 

to increasing appropriate exercise, boosting nutrition

awareness and habits, and decreasing disability.

Impact of Improved Health in the Elderly

There has been a decrease in the numbers of older

women suffering from disabling conditions and an

increase in life expectancy, perhaps reflecting changes

in nutrition and lifestyle as well as medical advances

such as the use of HRT. Studies should be undertaken

to investigate the social and physiological impacts of

women living longer—implications in the job market,

for example, as well as in the development of chronic

conditions and comorbidities.

Issues of Pharmacology and Aging

The Women’s Health Initiative is currently studying

nearly 165,000 women nationwide, with a major focus

on Hormone Replacement Therapy. This important

research study should be supported with additional

clinical studies on pharmacology.

• Identify toxic drug reactions in elderly women

associated with the use of concomitant medications, including HRT.

• Study drug interactions of commonly prescribed

medications, over-the-counter drugs, and nutritional supplements.

• Develop data-mining techniques to extract druginteraction information from existing databases.

• Investigate safe and effective alternatives to HRT.

Research Design and Methods

Before 1994, much of the data on drug use came

from studies that excluded women and elderly people.

As a result, physicians are currently prescribing drugs

on the basis of data that may or may not be relevant.
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Since that time, inclusion of women has been mandated

and studies have begun to collect data on women.

However, because of insufficient numbers of participants, the studies lack the statistical power to identify

gender differences. Changes in research design and

methods would address this situation.

• Develop data-mining techniques to extract from

existing databases critical health information pertinent to the health of elderly women; for example,

risk factors associated with certain conditions 

and the use of concomitant medications.

• Identify the toxic drug interactions associated with

the use of concomitant medications, including 

the concomitant use of HRT.

• Intensify federal guidelines regarding the inclusion

of women and minorities in research to ensure that

sufficient numbers are included to have statistical

power and to ensure that diversity can be addressed;

for example, subpopulations within ethnic groups

and institutionalized versus community-based 

populations.

• Develop better guidelines that focus on the regulatory and financial issues of conducting research 

on diseases, disorders, and conditions especially

prevalent in elderly women.

• Improve techniques to access existing databases

needed by investigators for exploring critical 

health issues in elderly women, including the use 

of appropriate key words for searching databases

like those of the National Library of Medicine.

• Conduct more research on the process and outcomes of obtaining more appropriate informed

consent from older women for research and 

medical procedures.

• Identify the barriers encountered by older women

that prevent them from joining research studies.

• Encourage the development, use, and evaluation 

of more creative and innovative research methods

and designs to study the health of older women.

• Foster multidisciplinary international collaborations and partnerships to conduct research on the

health of older women, including international

comparisons.

Education and Translation Issues

Key issues in education are the absence of teaching in medical schools about women’s health (except

for reproductive issues) and about aging. Efforts have

been made to rectify these omissions, but more commitment is needed. Curricula have been developed but

not yet fully implemented to study geriatric medicine.

Low socioeconomic status has been identified as 

a risk factor for poor disease outcome in the elderly.

However, research has identified critical areas that can 

be affected by education. Self-efficacy — a person’s

knowledge and belief that she or he can accomplish

certain things — is one area in which education can

affect behavior change. Chronic health problems can be

significantly ameliorated with appropriate intervention

and education; therefore, additional research is needed

to appropriately train lay leaders to teach self-efficacy

and other skills for managing health problems.

• Promote the use of lay leaders or others skilled 

in translating health information into language 

for consumers.

• Educate older adults about consumer rights 

and health care-related assertiveness.

• Develop education programs that emphasize 

lifelong learning and its importance in continuing a high quality of life.

• Educate managed care company personnel by

translating research findings and encouraging 

them to incorporate the results of such research

into their practice.

• Develop procedures that require outcome information from managed care organizations and 

translate that information for appropriate 

groups for policy decisions.

Plenary presentations

Michael D. Lockshin, M.D.

Director, Barbara Volcker Center

for Women and Rheumatic Disease

Professor of Medicine

WHY WOMEN? Hospital for Special Surgery-Cornell Medical Center

This article examines common suppositions about the reasons for female predominance in the autoimmune

rheumatic diseases. It suggests that estrogenic hormones are insufficient an explanation, and that further

work in the fields on environmental, genetic, chromosomal, and in utero sex differentiation is indicated.

The Hormone Hypothesis

Three concepts are now regnant: (1) autoimmune illnesses mostly afflict women; (2) autoimmunity, in

rheumatic diseases, is defined by autoantibodies; and (3) gonadal hormones drive autoantibodies and, therefore,

rheumatic disease. Gonadal hormones are thought to be the reason for the gender skew.1–4 This syllogism is the 

hormone hypothesis.

This paper argues against the hormone hypothesis for the reasons that autoimmune illness is not a single 

entity, rheumatic illness consists of more than autoantibodies, and the effects of hormones are too complex to 

yield so simple an explanation. Furthermore, gonadal hormones modulate autoimmune illness, but causation, 

and therefore gender ratio, is a different issue.

Table 1 lists five hypotheses about disease incidence and disease severity. Hypothesis 1 (gonadal hormones 

drive disease), absent a second (threshold) hypothesis, predicts more severe rather than more frequent disease 

in women. Hypotheses 2 through 4 predict equal severity and gender discrepancy, consonant with clinical data.

Few data bear directly on disease incidence. Much of what follows is speculation.

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TABLE 1. Five Hypotheses and Predictions About Incidence and Severity of Disease

Hypothesis* Effect on Susceptibility Ratio Effect on Severity

#1 Gonadal hormone increases autoantibodies Equal susceptibility m=f Women worse

#2 Gonadal hormone lowers threshold Women more susceptible f>m Equal severity (once threshold is passed)

#3 Gonadal hormone increases autoantibodies 

and lowers threshold Women more susceptible f>m Women worse

#4 Nonhormone factors lower threshold Women more susceptible f>m Equal severity

#5 Women exposed more Equal susceptibility f>m Equal severity

* For clarity, the hypothesis, “Gonadal hormone increases,” is shorthand for stating both alternatives, i.e., “estrogenic hormone increase or androgenic hormone lowers” 

for female predominant diseases. The inverse formulation would be valid for male predominant diseases. 
44

Why the Hormone Hypothesis May Be Wrong

Inflammatory diseases with skewed gender ratios usually have genetic or environmental causes. 

Skewed gender ratios are common in human illness (Table 2), but in most illnesses genes, behavior, and infections 

— not hormones — are either known or strongly suspected reasons for gender skew. There are other illnesses 

in which severity differs in men and women. In these as well, the reasons for the different phenotype are genetic,

not hormonal.

Some inflammatory rheumatic diseases with gender skew are not demonstrably autoimmune. Many

rheumatic diseases clinically and pathologically resemble the autoantibody (rheumatic) diseases, but intensive

search has to date documented the presence of only a few autoantibodies (anti-Scl-70 and p- and c-ANCA) or

immunogenetic traits (HLA DR3 or B27) and has failed to suggest a mechanism by which these autoantibodies

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

TABLE 2. Some Illnesses with Unequal Gender Ratios and the Putative Reasons

Illness Gender Cause

Known Cause

Lung cancer male smoking

Alcoholic cirrhosis male alcohol

Myocardial infarction male smoking, cholesterol, heredity, etc.

HIV male infection (sex practice, IV drug use)

Kuru female infection (cannibalism)

Leprosy male infection

Tabes dorsalis male infection

X-linked diseases male genetic

Putative Cause

Autism male specific (genetic?) brain injury

Spondyloarthropathies male genetic, infection?

Post-streptococcal nephropathy male infection

IgA neptiropathy male altered immunity

Unknown Cause

Autoimmune diseases: SLE, ITP, Takayasu, 

MS, primary biliary cirrhosis, thyroiditis, 

Graves’ disease female unknown

Scoliosis female unknown

Depression female unknown

Buerger’s male unknown

Goodpasture’s nephropathy male unknown

Fibrosing alveolitis male unknown

Lesser Disease in One Gender

Sickle cell anemia female genetic control Hgb F

RA, cardiopulmonary female unknown

Spondyloarthropathy female genetic, infection
might be pathogenic. The absence of defined autoantibodies in these illnesses needs explanation. It may be that the

right antigens have not been sought, or it may be that autoantibodies are not necessary for the clinical phenotype

defined by sterile arthritis, fever, rash, vasculitis, and possibly even glomerulonephritis.

Some chronic inflammatory diseases that clinically resemble autoimmune diseases have no gender

skew. Several chronic inflammatory diseases have no gender ratio skew (Table 3). Crohn’s disease, ulcerative 

colitis, and sarcoidosis have chronic inflammation, relapsing courses, and other features suggesting that they

should be subject to the same hormone modulation as the autoimmune diseases. In this case, however, there 

is no gender skew and no autoantibodies. If gonadal hormones induce or modulate autoimmunity, these illnesses ought to be explained.

Abnormal Gonadal Hormones Do Not Predispose to Autoimmune Disease

Patients with endocrinopathies do not have unusual susceptibility to autoimmune disease. Case series and a few 

controlled surveys from rheumatic disease clinics state that SLE patients are prone to develop thyroiditis and

Graves’ disease,5–7 but the converse does not seem to be true. Patients with Turner’s syndrome (XO female) 

develop thyroiditis but, estrogen-treated or untreated, not other autoimmune disease. Contemporary endocrinology texts mention a high frequency of schizophrenia in XXX females and of neoplasms in androgen-insensitivity

syndrome, but do not comment on occurrence of autoimmune disease in any gonadal hormone-abnormal patients.

Although rheumatology texts quote a high frequency of systemic lupus erythematosus among patients with Klinefelter’s syndrome (XXY male), endocrinology texts ignore this association note and instead report an excess of

chronic pulmonary disease, varicose veins, breast and lung cancers, and acute lymphocytic leukemia.8,9*

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* Absence of information is not proof. Nonetheless, an association between endocrinopathy and rheumatic illness is likely to be weak if 

it exists at all.

TABLE 3. Diseases Inconsistent with the Hormone Hypothesis of Autoimmune Disease

1. Chronic inflammatory diseases that clinically resemble autoimmune diseases but do not have skewed gender ratios

Ulcerative colitis

Crohn’s disease

Sarcoidosis

2. Chronic inflammatory diseases that have skewed gender ratios, but the skew is attributable to exposure

Reiter’s disease (male)

Tuberculosis (male)

Leprosy (male)

Tabes dorsalis (male)

HIV (male)

Kuru (female)

4. Inflammatory rheumatic diseases that have skewed gender ratios but are not demonstrably autoimmune

Ankylosing spondylitis (male)

Polyarteritis nodosa (male)

Wegener’s granulomatosis (male)

Scleroderma (female)

Takayasu’s arteritis (female)

5. Hormonal diseases that do not alter frequency or severity of diagnosable autoimmune disease

Thyroid disease (Graves’, thyroiditis)

X-Y chromosomal abnormalities (including Klinefelter’s syndrome and testicular feminization)

6. Hormonal interventions that do not demonstrably alter frequency or severity of autoimmune disease

Postmenopausal estrogen replacement

Leuprolide treatment

Estrogen treatment (male)
46

Hormonal interventions do not demonstrably alter frequency or severity of autoimmune disease. 

Large-scale epidemiologic studies have failed to demonstrate a marked increase in rheumatic disease among

women treated with either oral contraceptives or postmenopausal estrogen.10–12 Rheumatic arthritis is common 

after menopause more than before.13 Case reports and animal studies about castration and replacement lend 

credence to the idea that hormones modulate severity of extant autoimmune disease.14–16 They are less compelling regarding incidence or causation.

Little comment has been heard about whether women with lupus who suffer ovarian failure after cyclophosphanide treatment are more likely to remit than similarly treated women who do not suffer ovarian failure. There 

are no data on occurrence of autoimmune disease in castrated, estrogen-treated men, although many men are 

thus treated for prostate cancer. There are no reports of ameliorated rheumatic disease in patients treated with

leuprodile for endometriosis and other disorders.

Pregnancy. Rheumatic arthritis (RA) patients regularly enjoy remission during pregnancy. The concept that

remission is due to hormone, as opposed to other pregnancy changes, is under challenge.17 Many papers (not

all18) argue that pregnancy causes SLE to flare.19 The reason why pregnancy should cause opposite responses 

in SLE and RA, if gonadal hormones are responsible for female predominance of both diseases, has not been

addressed or answered. Pregnancy induces many non-hormonal physiological changes, for instance in the endothelium, vascular bed, and kidneys, which may be relevant to rheumatic disease.20 Although some of these 

changes may be under hormonal control,21 it is not necessary to invoke hormones to explain changing disease 

activity during pregnancy.

Nonhormone Explanations of Gender Skew

Gender Biology

X and Y Chromosomes

X and Y chromosome genes. The X chromosome contains genes that code for components of immune capability: those genes responsible for chronic granulomatous disease, Wiskott-Aldrich syndrome, severe combined

immunodeficiency (SCID), and agammaglobulinemia. Because a large number of X chromosome genes are still

unknown, it is no leap of logic to imagine that a to-be-discovered X-linked gene influences the gender ratio of

autoimmune disease. Because it is small and contains mostly sex-determining genes, a Y chromosome gene less 

likely down-regulates disease phenotype in men, but, in the BXSB lupus mouse, a Y-linked factor appears to 

be the cause of male predominant disease.22

Imprinted genes. An imprinted gene is one in which identical alleles code different phenotypes, depending

whether the gene’s origin is the father or the mother. A variant of imprinting is the inheritance of part or all of an

entire chromosome from one parent (uniparental disomy). Imprinting controls disease phenotype in BeckwithWiedemann syndrome (congenital overgrowth abnormalities and Wilm’s tumor), Huntington’s disease, insulindependent diabetes mellitus, and psoriasis. (For recent reviews, see Gregersen23 and Sapeinza and Hall.24) 

Chorionic villus sampling suggests that 1 percent of all pregnancies carry uniparental disomy for particular 

chromosomes. An hypothesis that predicts that gender skew will result from imprinted genes, or from mutations in imprinting genes, will be complex. Such an hypothesis is not a priori rejectable.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
X-inactivation. In order not to have a double dose of X chromosome genes, women inactivate (Lyonize) one 

X-chromosome. Which X — the paternal or the maternal — is selected for inactivation in a given cell line may 

be non-random. Women heterozygous for X-linked traits are normally mosaic (different cell types express either

the paternal or the maternal X). Five to 10 percent of normal women show skewing of X-inactivation toward 

one parent’s X, probably on a random statistical basis. Some X-chromosome genes do not participate in X-inactivation (review by Willard25). X-inactivation is controlled by the XIST (X-inactive specific transcript) gene. In some

families XIST function is abnormal, causing X-inactivation to be always non-random. Trisomy results from failed 

X-inactivation. In embryonic life, trisomy is not rare, but blastocystic cells can and do heal trisomy. By preferentially deleting an abnormal chromosome, this process may result in skewed X-inactivation.

Skewed X-inactivation is responsible for the variable clinical phenotypes of X-linked diseases, such as LeschNyhan syndrome, Wiskott-Aldrich syndrome, SCID, and agammaglobulinemia. X-inactivation is a sufficiently 

powerful and variable process that identical twins can be discordant for heritable disease, such as Duchenne 

muscular dystrophy, on the basis of selective X-inactivation alone. Scenarios can be constructed in which an

autoimmunity gene resides on the X-chromosome and is subject to non-random inactivation or is not activated 

and causes a high female:male ratio of illness.

X and Y chromosomes determine gender-specific anatomy and physiology, including hormones. Genes 

on the X or Y chromosomes constitute the major alternative hypothesis for gender-discrepant illness.

Non-gonadal hormones. The influences of prolactin,26,27 corticotrophin-releasing hormone, and thyroid 

hormones28 in autoimmunity have been reviewed elsewhere. These hormones are closely linked to the action 

of gonadal hormones but are separate entities whose role is now being explored.

Gender-specific exposures. Sexually active women have gender-specific exposure to sperm, pregnancy hormones and products, and circulating fetal cells. Because autoimmune diseases occur in girls and women with 

no prior sexual or pregnancy exposure, such exposure cannot be obligate causes of illness.

Beeson used epidemiologic evidence to argue that the hormone hypothesis is insufficient to explain gender

skew, but offered no alternative hypothesis.29 Nelson suggested that maternal immune response to fetal HLA

induces the remission characteristic of RA pregnancy.17,30 Mullinax and others suggest that circulating fetal 

cells induce scleroderma, postulated to be a form of graft-versus-host disease.31,32 However, pregnancy-based 

hypothesis such as these fail to account for illness in non-transfused children, nulligravidas, and men.

Gender-specific (nonhormone) physiology. By virtue of menstrual loss, mature, pre-menopausal women may 

be chronically less iron-replete than men. Pregnancy changes, whether or not linked to pregnancy hormones, 

may trigger other physiologic adaptations that alter expression of disease. Ligamentous loosening in late pregnancy, for example, may stress inflamed joints and cause the inflammation to increase.

In many small ways, female and male physiology differ. Preterm and term newborn boys have demonstrably

less developed hearing mechanism than do girls. 33 Neuroimaging demonstrates anatomic and physiologic differences between male and female brains.34–36 These differences are not directly relevant to autoimmune disease, 

but they do demonstrate that the genders differ in surprising ways. More obviously relevant, immune competence

itself may be driven by neuroendocrine mechanisms that differ between men and women.37,38

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48

Cultural differences between women and men, such as aggressiveness or direction-finding by landmark or 

vector clues, may be biological rather than learned.39 Recent studies suggest that pentazocine and related kappaopiates produce better analgesia in women than in men.40 These pharmacological differences are of sufficient 

magnitude that they could, speculatively, influence disease frequency or phenotype by altering processing of 

an as yet unknown toxin chemical. Admittedly, these types of gender differences may result from gonadal 

hormones, but they may also be independent phenomena.

Intrauterine events may influence a fetus’ post-natal gender biology. Monozygotic twins differ importantly, for

instance in gene imprinting, more if they share one placenta, demonstrating that acquired characteristics, including

gender characteristics, can be modified very early in early embryonic life.41 In the bicornuate uteri of rats, male

fetuses located caudally or between female fetuses later display more ambiguous sexual behavior than do male

fetuses located between male fetuses or cephalad. In gerbils, females located in utero between male siblings have

masculinized anatomy and behavior, and subsequently produce more male pups than do females who are located

in utero between females.43,44 In humans, dizygotic twin women whose twin is male may be more masculine than

are women whose dizygotic twin is female.45 These influences on gender might also influence disease susceptibility.

Gender-specific anatomy. Claims of anatomic differences between men’s and women’s brains and between 

brains of heterosexual and homosexual men have received wide press.46 The differences (if they exist) may 

be gene-, development-, or hormone-driven. Anatomic patterns of lymphatic drainage from the genitourinary

organs (in closer proximity to the vertebral column in males) remains an open hypothesis concerning different 

outcomes with ankylosing spondylitis in HLA B27 positive men and women. More subtle anatomic differences

between men and women, for instance, relative quantities of fat, muscle, or bone, whether or not caused by 

hormones, may in as yet not understood ways influence disease susceptibility or expression. The relationship 

among estrogens, body fat, and osteoporosis in women athletes is a case in point.

Biological clocks. The effects of biological clocks on health and illness is a new field of inquiry. The menstrual

cycle is obvious evidence that women’s and men’s clocks differ. Non-gonadal hormones participate in short and

long-term cycling, for instance melatonin in circadian rhythms and leptin in triggering puberty.47 It is not known

whether the fact of cycling itself, rather than the specific levels of hormones undergoing cyclic variation, is important. Many immune and endocrine functions vary diurnally.48 Diurnal and seasonal rhythms influence onset and

prognosis of many diseases.49 Lupus activity possibly varies with the menstrual cycle.50 To distinguish the effect 

of long-term cyclicity independent of the hormones undergoing cycling would be a very difficult experiment to

perform. Nonetheless, the effects of disrupting diurnal cycles on health are broad. That women and men have 

different health experiences attributable to their different biological clocks is a reasonable, testable hypothesis.

Medical experience of homosexuals. There is increasing consensus that homosexuality has biological rather than

psychological origins. Assuming this consensus is correct, and ignoring for the moment the seminal fluid and

infectious agent exposure differences that distinguish homosexual men from heterosexual men, a different biology 

of homosexuals from heterosexuals might result in different disease experiences. Some papers have commented 

on worse, and possibly more frequent, Reiter’s disease in male HIV-infected homosexuals,51 attributing disease

expression to HIV rather than to some other aspect of sexual practice. No literature exists on conventional 

autoimmune disease (as opposed to autoantibodies) in male homosexuals.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Male and Female Illness Phenotypes May Differ

Defined by advanced spinal ankylosis, ankylosing spondylitis is an uncommon disease, of which the victims

are 90 percent men. Defined by modest low back pain and radiographic sacroiliitis, the disease occurs equally in

genetically susceptible men and women.52 Either of two interpretations is possible: men have more severe disease

(more often pass the clinical threshold, spinal ankylosis, that leads to diagnosis), or women with the illness are

misclassified. The former interpretation is likely, making ankylosing spondylitis one of the few rheumatic (but 

not autoimmune) illnesses consistent with hypothesis 1 of Table 1.

X- or Y-linked (non-hormone) genes may explain gender-related differences in severity of disease. In sickle 

cell anemia, the F-cell production locus, an X-linked gene, regulates the production of hemoglobin F,53 high 

levels of which protect against erythrocyte sickling. As a result, girls have less severe sickle cell disease, and 

survive longer, than do boys.54

Gender Skew May Have a Cultural Cause

The influence of culture on gender ratios can be dramatic. In depression, female predominance is the rule, 

but in different cultures gender ratios range for depression from 1.5:1 to about 4:1.55 Schizophrenia occurs 

world-wide, but different phenotypes (hebephrenia, catatonia) vary strikingly in incidence and gender distribution, suggesting that onset of schizophrenia is dictated by biology but its phenotype is dictated by culture.56

Kuru had a 3:1 female predominance because Fore women, but not men, ate the brains of recently deceased 

tribe members.57 Women with or around small children have different infectious disease exposures than do 

men. Hypotheses that hair dye or lipstick cause lupus, frivolous as they seem, have been seriously tested but 

found wanting.58,59 Women culturally differ from men in many ways, including diet, social contacts, contraceptives, and use of sanitary products, to name a few. Hormones are subject to cultural control: the amenorrhea of

women athletes is an example. If dominant and subordinate hamsters are caged together, subordinate dams have

far smaller litters and far fewer male pups than do dominant dams, probably because the stress of being dominated reduces prolactin secretion.60 Women’s stress hormone thermostat is set differently from that of men, leaving

open the suggestion that the different setting can be invoked to explain gender discrepancy of disease.2,37,61

Much of the preceding information is based on non-definitive studies. Nonetheless, this information argues

that non-hormone aspects of gender may be powerful determinants of biological health, and, by extension, of 

illness of phenotypes.

Where Next?

Deconstruct the Autoimmune Disease Are Women’s Diseases Argument

The question of why autoimmune (rheumatic) illness preferentially select women remains important. The

terms of the question, however, may not be valid. Autoimmune diseases are not monolithic. The pathogenesis of 

a disease like SLE may be very different from that of rheumatoid arthritis, and both may be very different from

scleroderma, yet they are all called autoimmune. Other than autoantibodies, there is no intuitive reason to link

organ-specific autoimmune diseases like thyroiditis with systemic illnesses. Diseases that attack young women

(SLE) may have a completely different relationship to gonadal hormones than do diseases that attack older 

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50

women (RA). Even were one to attribute female predominance of autoimmune disease to a single cause, for

instance gonadal hormones, the up-regulation and down-regulation of different components of the immune 

system is exceedingly complex and delicately balanced. A single, unifying hypothesis may not be possible.

The basic facts — the gender ratios themselves — need better quantitation. Additional data on the influence of castration or hormone manipulation in human disease will be helpful.

Consider Nonhormone Aspects of Gender

Alternatives to the hormone hypothesis, and explanations that acknowledge the differences between incidence

and severity of illness, are needed. Might autoimmunity be only a female-specific phenotype of a more general illness? Might spondyloarthropathy and autoimmune disease be essentially the same illness presented in male and

female contexts? What are the roles of imprinted genes or X-inactivation? Have environmental causes for the

skewed gender ratios been fully excluded?

Understand the Difference Between Disease Initiation and Disease Modulation, or the Difference Between 

Incidence and Severity. Is a Threshold Operative?

To raise alternative suggestions is not to ignore a plethora of published evidence that gonadal hormones 

influence autoimmunity.13 Animal models of autoimmunity constitute one of the strengths of this literature.22

Another strength is that experimental animal autoimmunity can be modulated by castration and by administration of gonadal hormones. Studies of the effects of pregnancy on immune function add further support, as do

reports that exogenous hormones alter disease activity in humans. However, the available evidence speaks far 

more strongly to modulation of disease by hormones than it does to the role of hormones in causation of disease. 

It speaks to disease properties that can be manipulated for patients’ good, but it does not answer the gender 

ratio question, why is autoimmunity a woman’s disease?

Acknowledgments

I am grateful for discussions with Drs. Richard Lockshin, Zahra Zakeri, Vivian Pinn, Ronald Wilder, Daniel

Kastner, Peter Gregerson, and Barbara Mittleman, Kirt Vener, and Ms. Amanda Lockshin, all of whom helped 

me develop these thoughts.

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PSYCHOLOGICAL DIFFERENCES BETWEEN WOMEN 

AND MEN: IMPLICATIONS FOR A RESEARCH AGENDA Vickie M. Mays, Ph.D.

ON WOMEN’S PHYSICAL AND MENTAL HEALTH University of California, Los Angeles

My task is twofold. First, I will present an overview of the gender differences in mental disorders. The

second, which I consider the most critical, is a discussion of how the psychosocial context contributes

to differences in women’s health status and how their health behaviors and the implications of these

differences impacts the development of a research agenda with the goal of providing gender-specific treatment for

women. I have been asked to use and given permission to employ as the foundation for my remarks two American

Psychological Association (APA) publications. The first is entitled Research Agenda for Psychosocial and Behavioral

Factors in Women’s Health (APA, 1996). The second is entitled Health Care for Women: Psychological, Social and 

Behavioral Influences (Gallant, Keita, and Royak-Schaler, 1997).

Psychosocial and Behavioral Factors that Contribute to Gender Differences in the Physical Health 

Status of Women

Despite an increased focus on the medical, biological, and epidemiological aspects of women’s health, research

has not adequately highlighted the central role that psychosocial and behavioral factors play in contributing to

these differences in women’s health status (APA, 1996) or the role they could play in the management of these

chronic diseases. If we are to conduct research that is meaningful to women, we must not be fooled into thinking 

we have solutions when we merely successfully document differences in the rates and risks of diseases in women.

Rather, it is important that we ask why these differences exist and search for the factors that brought about these

differences. It is important that each of us remembers that a woman’s health is a function of complex interactions

between her personal behaviors and the economic, social, and physical environment in which she lives and works

(Brown et al., 1996). While a woman’s knowledge and attitudes are important components that influence her

health-related behaviors, her behaviors are also strongly influenced by supports and barriers that she encounters 

in her personal intimate relationships, her friendship networks, her community, and her interactions within society

(Brown et al., 1996). As an example, a 17-year-old woman struggling with an eating disorder is struggling against

the societal message that thin is pretty, a social group norm among her friends that thin is popular, and, at times,

the social reality that thin gets Mr. Right.

The focus of our research on women’s health should also be on understanding how the experiences of different

groups of women affect health-related issues, rather than on simply documenting differences between women and

men as distinct groups. Health needs, barriers to obtaining services, styles of coping, or the basis for well being

may vary among diverse cultural and socioeconomic groups (APA, 1996). It is important to remember that women

are a heterogeneous group whose experiences may vary with ethnicity, race, marital or relationship status, parental

status, education, income, occupation, sexual orientation, the type of job we hold, and where we live (APA, 1996).

Where women live should no longer be reduced to urban versus rural but rather should include a focus on the

quality of their neighborhoods. Do they live in neighborhoods with a high rate of violence, little public transportation, and few grocery stores with fresh produce? Sometimes not getting a prescription filled after leaving the 

doctor’s office at 5 p.m. has more to do with the fear of getting home in the dark in a neighborhood where robbery

and drive-by shootings are more commonplace than non-compliance or cultural conflicts with a health directive.

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Physical Health and Psychological Experiences

It is important in our research on women’s health that gender-related psychological, behavioral, and social 

factors be examined within their interrelationships with biomedical factors (APA, 1996). Like ethnic status, 

social class, and age, gender is also associated with social realities that are different for women and men.

One area that illustrates the relationship between a physical and psychological experience is in the victimization of women. Table 1 offers insight into the link between violence and physical and/or psychiatric disorders

(Mellman and Bell, 1996). Victimization, particularly in its physical forms, appears to have long-term mental

health consequences (Glied and Kofman, 1995). Glied and Kofman found that major depression is two to three

times as common among women who report that they have experienced a sexual assault (including child sexual

abuse) in contrast to those who have not been victimized. Mellman and Bell (1996), in examining the consequences of violence, cite several studies that document higher rate of visits to physicians by victims of violence. 

In one study of rape victims, it is reported that the victims of violence had an 18 percent increase in physician visits in the year of the assault, 56 percent in the next year, and 31 percent in the following year compared with the

women’s pre-assault level. There are a host of psychiatric disorders (e.g., alcohol and drug abuse or dependence,

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TABLE 1. Summary of Psychiatric, Behavioral, and Physical Effects of Violence Against Women

Short Term

Psychiatric and Behavioral Physical

Acute stress disorder Broken bones, bruises, cuts

Short or Long Term

Psychiatric and Behavioral Physical

Depression, low self esteem Miscarriage

Suicide attempts Preterm labor

Substance abuse Fetal injury

Self-mutilation Rupture of uterus, spleen, or liver

Running away Sexually transmitted diseases

Anxiety Hearing or vision loss

Pain

Physical complaints

Long Term

Psychiatric and Behavioral Physical

Posttraumatic stress disorder Chronic headaches

Dissociative disorder Low-birthweight babies

Multiple personality disorder Functional bowel disorder

Stormy interpersonal relationships Death by homicide

Revictimization
56

panic disorder, obsessive-compulsive disorder, and posttraumatic stress disorder) that are found more frequently 

in persons with a history of sexual assault. In thinking about the differences in the health and mental health of

women and men, studies like the above highlight the contributions that the social context of women’s lives play 

in their physical or mental health status.

For the most part, the leading causes of death for women and men, if they live long enough, are heart diseases

and cancers (see Table 2; Leiman, et al., 1997). However, there are gender differences in the pattern of mortality. 

A number of explanations have been offered to account for these gender differences. Some of these include the 

role of biology, technological advances in health care, stress exposures, stress responses, and differences in lifestyle

(Woods, 1995). Yet, lost in this comparison is that life expectancies are not the same for all women. Currently,

there is an almost 6-year difference in the life expectancy between white and African-American women (Woods,

1995; NCHS, 1993). Across the board, with the exception of Asian women, heart disease is the number one cause 

of death for women, followed by cancer, with diabetes, pneumonia and influenza, and cerebrovascular and chronic

lung diseases bringing up the rear (Table 2; Leiman, et al., 1997). Despite a steady decline in the rate of cardiovascular disease mortality in the United States since the 1980s, heart disease is still the number one cause of death in

American women (Leiman, et al., 1997). Women also have a worse prognosis for survival after myocardial infarction (MI) than men, and African-American women have the worst prognosis of all (APA, 1996). The research 

agenda for women’s health must accommodate studies drawn from a variety of methodological approaches to 

explicate the causal mechanisms linking psychological, behavioral, and physiological processes in disease. For

example, APA (1996), in its behavioral research agenda on women’s health, suggests several areas of research 

that focus on the psychological mechanisms in cardiovascular disease in women. It would be well to broaden 

the research agenda to include these psychosocial studies in cardiovascular disease.

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TABLE 2. Leading Causes of Death for Women and Men, 1993

Women Rank Men

Heart diseases 1 Heart diseases

Cancer 2 Cancer

Cerebrovascular diseases 3 Accidents and unintentional injuries

Chronic obstructive lung diseases 4 Cerebrovascular diseases

Pneumonia and influenza 5 Chronic obstructive lung diseases

Accidents and unintentional injuries 6 Pneumonia and influenza

Diabetes 7 HIV infection

Nephritis 8 Suicide

Septicemia 9 Diabetes

Atherosclerosis 10 Homicide

Source: P. Gardner and B.L. Hudson. “Advance Report of Final Mortality Statistics, 1993.” Monthly Vital Statistics Report. Hyattsville, MD: Centers for Disease Control and

Prevention, National Center for Health Statistics, 44 (7s), 1996.
Litt (1993) presents health problems that are more common in women than men (Table 3). Beside the 

psychiatric categories, several of the health problems, rheumatoid arthritis, asthma, lupus, and even cardiovascular disease, are influenced by a variety of behavioral and psychological factors. Woods (1995) gave us a good 

context to think about differences in patterns of morbidity between women and men. Women and men are

exposed to different risks of disease as a function of differences in the jobs they occupy in society, which not 

only provide differences in exposures but also access to health care through private insurance. There are also 

gender differences in lifestyle, socialization of response to illness, use of health services, and the stress exposures 

of women, especially for ethnic women as their ethnicity acts as a marker for social experiences like racism

(Woods, 1995). So clearly a woman’s health status is not just a matter of genetics.

Psychological and Behavioral Factors and Physical Health Status

Psychological and behavioral factors are important predictors of well being, vulnerability to disease, and 

disease outcomes (APA, 1996). For example, studies have begun to document that the negative emotions of 

psychological distress, anxiety, anger held in, and depression are psychological variables that can influence the

course of postmyocardial infarction (see Knox and Czajkowski, 1997 for a fuller discussion). Recent research 

has suggested that each of these negative emotions may influence behavior, thrombogenesis, and arrythmogenesis 

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TABLE 3. Health Problems More Common In Women Than Men

Health Problems Number of Women (Percent)

Musculoskeletal-connective tissue 37 million

Osteoporosis 20 million (80)

Juvenile rheumatoid arthritis 61,000 (86)

Osteoarthritis 11.7 million (74)

Rheumatoid arthritis 1.5 million (71)

Systemic lupus erythematosus 450,000 (90)

Cardiovascular (82 percent of women aged 45 to 74 years vs. 71 percent of men)

Hyperlipidemia

Hypertension 16 million (58)

Kidney/urologic

Incontinence 9.6 million (80)

Neurologic

Migraine 12 million (70)

Glaucoma 1.5 million (67)

Psychiatric

Depression (9.7 percent of women vs. 4.7 percent of men)

Bulimia 7 million (87)

Respiratory

Acute bronchitis 5.3 million (60.5)

Asthma 6.02 million (53)

Influenza 66 million (54)

Source: Pharmaceutical Manufacturers Association, New Medicine in Development for Women (Washington, D.C.: Pharmaceutical Manufacturers Association, 1991).
58

in a variety of ways. Frasure-Smith and her colleagues (1996 ) suggest examining whether anxiety may be more

important than depression or held-in anger in accounting for thrombogenesis, while depression and anger may 

be crucial psychological factors in arrhythmic events. As presented later, both anxiety and affective disorders,

which include depression, are more prevalent in women than men.

Quality of Life

Quality of life is an important outcome measure and includes a sense of well being, functional health, and

engagement in the psychological and social world (APA, 1996). One area that illustrates the gender differences in 

the quality of life for women is rheumatoid arthritis. Arthritis is among the most common self-reported chronic

condition affecting women (see APA, 1996, for fuller discussion). Many of the more common and also debilitating

forms of arthritis and rheumatic disease (e.g., osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus,

fibromyalgia) affect two to five times more women than men (APA, 1996). DeVellis and her colleagues report that

people with rheumatoid arthritis experience difficulty in leisure and religious activities, visiting family and friends,

and using different forms of transportation (DeVellis, Revenson, and Blalock, 1997). DeVellis, et al. cite a study 

by Reisine and Fifield (1992) that illustrates differences in the impact of these difficulties on the quality of life of

men and women. More men reported difficulties in their abilities to do yard work and care for the car. For women

however, their arthritis had an impact on nurturant activities such as making arrangements for others, taking them

places, maintaining social ties by writing or calling, listening, and taking care of sick people. Women who experienced these type of limitations were less satisfied with their ability to be a nurturant support provider.

In two previous reviews by DeVellis (1993, 1995), she finds that depression and/or depressive symptomatology have a high co-occurrence in persons diagnosed with rheumatoid arthritis. Research suggests that people with

serious chronic diseases are at greater risk for developing depressive disorders and symptoms (Wells, Golding, and

Bumam, 1988, in APA, 1996). When depressive symptoms occur in combination with other chronic diseases, levels of functioning decrease (Wells et al., 1989). As the APA agenda so aptly points out, as women are at greater risk

for depression and for some of the more debilitating forms of arthritis and rheumatic disease, they bear a double

burden of potential disability (DeVellis, 1993). A better understanding of the scope and impact of depression in

arthritic and rheumatic diseases as well as research on how to prevent and treat depression in this population 

is needed (APA, 1996). Of course, it is not surprising that when depression occurs with a health condition like

rheumatoid arthritis, the decline in functioning is worst (DeVillis, et al., 1997). We already know that the rate 

of depression in women is about twice that of men. For women with rheumatoid arthritis, if depression is mistakenly overlooked, declines in functioning may be attributed to the rheumatoid arthritis and not treated, while 

the rheumatoid arthritis is overtreated. In addition to gender differences in response to this disease, two studies

seem to indicate cultural differences as well (Abraido-Lanza, in press; Abraido-Lanza, Guier, and Revenson, 1996).

Abraido-Lanza in her study of Latina women suffering from rheumatoid arthritis found not only were these women

likely to exhibit depressive symptomatology but also their coping responses reflected a culture-based notion of

coping and culturally valued norms that they turned to for help. As epidemiological studies have consistently

demonstrated worse health outcomes among women with arthritis and rheumatic diseases, especially for ethnic

minority and lower socioeconomic groups, it is important to determine what mechanisms are at work. As illustrated

in Abraido-Lanza’s studies, cultural differences may play a defining role in how women manage their health care.

Other potential constructs that could explain these relationships include stress, social support and coping mechanisms, and access to health care, as well as differential treatment patterns.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Contextual Contributions to Gender Differences in Women’s Health Status

There are a series of contextual factors that should be considered in designing, implementing, and interpreting research if the goal is discovery of gender-specific conditions of women’s health. This approach will 

help to enhance traditional biomedical research and offer new insights (APA, 1996). There are contexts that 

behavioral research findings imply may be critical to consider in the development of a gender-specific research 

agenda for women.

Relationships

How do women’s relationships affect health status, health behaviors, and health attitudes? How do health

behaviors, attitudes, and health status affect women’s relationships (APA, 1996)? We know that being married is

more advantageous to men’s health than women’s health. Marriage appears to confer a protective advantage against

depression for men, which is less true for women (McGrath, et al., 1990). In unhappy marriages, women are three

times more likely as men to become depressed (Weissman, 1987; McGrath, et al., 1990). Marital disruptions are

not good for either sex, but women seem to suffer the most (see Glied and Kofman, 1995, for a fuller discussion).

Glied and Kofman cite research that indicates that those who are separated or divorced are 2.5 times more likely

than married people to suffer a depressive disorder (Regier, et al., 1988). Those women who experience marital

disruption were found to have rates of depression 3.1 times higher than happily married women, 2.1 times higher

than unhappily married women, and 1.7 times higher than women who were already divorced or separated (Bruce

and Kim, 1992, in Glied and Kofman, 1995). For men, the protective effect of a continuing happy marriage is even

stronger (Glied and Kofman, 1995).

There are other studies on relationships that raise questions on the extent to which women’s caretaking and

provider roles in the family have resulted in their own health care needs being delayed or ignored. In their role 

as caretakers of children and parents, we find that vulnerability to demoralization and depressive symptoms to be

higher in mothers of young children; women who have responsibilities to care for aging parents are also at higher

risk (McGrath, et al., 1990). Similar stresses also affect those caring for medically or mentally ill family members

(Thurer, 1983). Knox and her colleagues note that fewer women, for example, attend and adhere to cardiac rehabilitation programs (Knox and Czajkowski, 1997). They suggest that this may be a function, to a greater extent for

older women, of lifestyle constraints, as the women are more likely than men to have caregiving burdens. Social

support and social isolation are important in coronary artery disease and postmyocardial infarction. Social isolation, which is defined as lacking an intimate confidant, having few friends or social activities, or not having access 

to practical assistance when needed in everyday situations, has been associated with cardiovascular mortality (Knox

and Czajkowski, 1997). It is important to remember that women live longer than men, and, therefore, when they

suffer from the problems associated with heart disease, they may be living without a spouse.

As a psychologist, it is also important that I discuss the concept of negative social support. Not all social 

support has a positive effect, so assuming that a person has a network of people does not always imply that the 

network is furnishing positive helpful support. What can be found is that even when women are sick and or 

disabled, they still are in the caretaking and head of household role in which their nurturance, guidance, and 

support are relied upon and needed to maintain their family system. This may result in their own health care 

needs receiving lower priority.

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Ethnicity

How do women’s ethnic backgrounds shape their health, health behaviors, and attitudes (APA, 1996)? 

Abraido-Lanza’s studies of Hispanic women’s coping with rheumatoid arthritis is an example of how culturally 

valued norms and culturally based notions influence the coping process.

Resources and Status and Power

There are the two additional elements, namely resources and status and power. How do financial and structural resources enhance or limit women’s health options? (APA, 1996). How do women’s social status, work status,

and power within relationships limit health options or affect health status? Epidemiological studies have repeatedly

shown a relationship between socioeconomic status (SES) and coronary heart disease (CHD) with poorer populations suffering from higher rates of CHD. It is thought that lifestyle behaviors are associated with lower SES populations such as unhealthy diets, higher rates of smoking, and health behaviors, i.e., higher rates of obesity. More

recent research shows a larger proportion of chronic physical and psychosocial stressors, such as jobs with high

demand and low decision latitude, low social support, high job dissatisfaction, unemployment, residential areas

with high crime rates, and poor access to medical treatment among people with low socioeconomic status. Many 

of these psychosocial factors are related to cardiovascular risk.

Gender Expectations

The final contextual issue presented by APA is gender expectations: how is health status affected by gender

expectations, such as expectations for mothering/primary parenting and caregiving for others who are sick or in

need, expectations to serve as an emotional support system for others, and expectations for housework and other

household tasks. Women are usually supportive in helping implement lifestyle changes for their husbands and

other family members (e.g., dietary changes, exercise, and stress reduction) that are necessary for increasing the

probability of survival. However, the lifestyle changes that are important for women’s own rehabilitation of CHD

may engender negative responses from immediate family members because these changes may conflict with gender

role expectations of women (e.g., traditional caretaker and nurturer). Research is needed that examines the effect 

of these gender role expectations on the ability of women to affect and maintain health-related lifestyle changes

and the subsequent effect on quality of life, depression. and disease course.

Gender Differences in Mental Health Occurrences

Turning now to the first charge, I will say a few words about gender differences in mental health status. First,

an important and surprising finding that emerged from the data collected by the Epidemiology Catchment Area

study was that men and women are equally likely to suffer from mental disorders. This finding has been underscored in the more recent National Comorbidity Survey (Kessler, et al., 1994). Prior to the 1980s, small-scale 

studies were likely to indicate that women had a higher prevalence of mental illness than men, accounting for the

perspective that we still encounter that mental illness is a woman’s issue. However, while men and women may 

in equal numbers suffer mental illness, the patterns and types of illnesses as well as responses to treatment differ

profoundly and have significantly different implications in terms of their impact on the lives of women and men.

To look at these differences, I have combined data from National Comorbidity Study and the Institute of 

Medicine’s 1991 report. Figure 1 shows that women are more likely to have anxiety and affective disorders (with

the exception of mania), while men are found in greater numbers to be diagnosed with antisocial personality and

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
substance use disorders (Kessler, et al., 1994). In the area of anxiety disorders, the lifetime prevalence of phobias

for men is about 10 percent, while women is 18 percent (Glied and Kofman, 1995). The same approximately 2 

to 1 women to men pattern is found for generalized anxiety disorders (Glied and Kofman, 1995). One area not 

on the chart is eating disorders. Approximately 90 percent of those diagnosed with eating disorders are women.

Looking at the affective disorders, women are significantly more likely than men to suffer from this debilitating health problem. Depression is one of the nation’s most serious mental health problems. People suffering from

depression experience reductions in functioning as severe (and sometimes more severe) as those associated with 

a variety of serious medical conditions including hypertension, diabetes, and arthritis (Wells, et al., 1989). Depression that is untreated can linger for 6 months or longer, and is likely to recur (APA, 1990). APA’s Task Force on

Women and Depression estimated in 1990 that more than 7 million women in the United States were suffering

from a diagnosable depression (McGrath, et al. 1990). Lifetime rates of depression in women as compared to 

men in both the ECA and NCS are two to three times greater. Consequently, research on depression should be 

a major focus of a women’s health research agenda.

Differences in the rates of depression between women and men are found in every age group among blacks,

whites, and Hispanics after controlling for income, education, and occupation (Glied and Kofman, 1995; McGrath 

et al., 1990). The Commonwealth Fund Women’s Health Survey found that not only is depression more severe 

in women than men, but that the percentage of women reporting severe depression was highest in Hispanic followed by African-American women (see Figure 2). Younger women were more likely to report severe depression

(see Figure 3), and poor women were the most likely to report severe depression (see Figure 4). Several studies

show an increasing prevalence of major depression in younger age groups, with the onset of depression now 

occurring in the teenage and early adult years (Regier, et al., 1988). Increasing experience of life events and loss 

of attachments, shifts in family structure, women’s changing position in society, and increasing social anomie 

have been put forward as possible explanations for this trend (Weissman and Klerman, 1977, 1992). Biological 

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■ Men

■ Women

0% 5% 10% 15% 20% 25%

Anxiety Disorders

Panic disorder

Somatization

Phobias

Obsessive compulsive disorder

Generalized anxiety disorder

Affective Disorders

Dysthymia

Major depression

Bipolar disorder

Substance Use Disorders

Drug abuse

Alcohol abuse

Other Disorders

Antisocial personality

Schizophrenia

FIGURE 1. Lifetime Prevalence 

of Psychiatric Disorders in 

Women and Men

Source: Kessler et al., 1994, Arch Gen Psych.

Weissman, IOM Report, 1991.
62

susceptibility, sociocultural and psychosocial explanations, and reproductive and endocrine-related factors 

have been advanced as explanations for the preponderance of depression in women, but, according to the 

APA Depression Task Force, these theories cannot fully account for the observed gender differences (Weissman 

and Klerman, 1977; McGrath, et al., 1990).

Recently studies have identified gender differences in how men and women synthesis serotonin (Nishizawa, 

et al., 1997). The rate of serotonin synthesis was found to be 52 percent greater in men than women, which may

have implications for the higher incidence of major unipolar depression found in women (Nishizawa, et al., 1997).

Equally a problem is the fact that little research has focused on differential treatment response patterns to pharmacological treatments for major depression in women and men (APA, 1996; Glied and Kofman, 1995). Response 

to psychopharmacological treatments can be considerably affected by psychosocial experience and hence has 

an implication for differences in response between men and women.

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

■ Men

■ Women

Total

Percent of Women with Severe Depression Within Last Week

White African

American

Hispanic

60

50

40

30

20

10

0

FIGURE 2. Severe Depression By Gender

and Race/Ethnicity

Derived from ranking responses to six statements 

regarding symptoms of depression.

The Commonwealth Fund Women’s Health Survey

Louis Harris and Associates, Inc., 1993.

Total Women

Percent of Women with Severe Depression Within Last Week

18 to 44 44 to 64 65 & Older

50

40

30

20

10

0

FIGURE 3. Women and Depression:

Younger Women are More Depressed 

than Older Women

Derived from ranking responses to six statements 

regarding symptoms of depression.

The Commonwealth Fund Women’s Health Survey

Louis Harris and Associates, Inc., 1993.

Race/Ethnicity

Age
These gender differences in psychological disease as well as gender differences in psychosocial aspects of 

the disease process are critical variables for study in a new research agenda focused on women’s health.

References

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Abraido-Lanza, A.F., Guier, C., and Revenson, T.A. (1996). Coping and social support resources among Latinas with arthritis.

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Bruce, M.L., and Kim, K.M. (1992). Differences in the effects of divorce on major depression in men and women. Am J 

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DeVellis, B.M. (1993). Depression in rheumatologic diseases. Balliere’s Clin Rheumatol 7:241–58.

DeVellis, B.M. (1995). Psychological impact of arthritis: Prevalence of depression. Arthritis Care Res 8:284–89.

DeVellis, B.M., Revenson, T.A., and Blalock S J. (1997). Rheumatic disease and women’s health. In S.J. Gallant, G.P. Keita, 

and R. Royak-Schaler (Eds.) Health care for women. Psychological, social, and behavioral influences. Washington, D.C.: 

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Gallant, S.J., Keita, G.P., and Royak-Schaler, R. (1997). (Eds.) Health Care for Women: Psychological, Social, and Behavioral 

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Glied, S. and Kofman, S. (1995). Women and mental health: Issues for health reform. New York, NY: Columbia University, 

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Percent of Women with Severe Depression Within Last Week

Food

Stamps

$7,500

& Less

$50,001

& Up

80

70

60

50

40

30

20

10

0

FIGURE 4. Depression and Income 

Levels: Poor Women on Public 

Assistance Most Vulnerable

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regarding symptoms of depression.

The Commonwealth Fund Women’s Health Survey

Louis Harris and Associates, Inc., 1993.

Annual Family Income/Public Assistance

SSI/

AFDC

$25,001-

$50,000

$15,001-

$25,000

$7,501 -

$15,000
64

Greenberg, P.E., Stiglin, L.E., Finkelstein, S.N., and Berndt, E.R. (1993). The economic burden of depression in 1990. 

J Clin Psychiatry 54:405–418.

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(1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the 

National Comorbidity Survey. Arch Gen Psychiatry 51(1):8–19.

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women. In S.J. Gallant, G.P. Keita, and R. Royak-Schaler (Eds.) Health care for women: Psychological, social, and behavioral 

influences. Washington, D.C.: American Psychological Association. pp. 257–72.

Leiman, J.M., Meyer, J.E., Rothschild, N., and Simon, L.J. (1997). Selected facts on U.S. women’s health: A chart book. 

New York, NY: Columbia University, The Commonwealth Fund, Commission on Women’s Health.

Litt, I.F. (1993) Health issues for women in the 1990s. In S. Matteo (Ed.), American women in the nineties: today’s critical 

issues. Boston, MA: Northeastern University Press. pp. 139–57

McGrath, E., Keita, G.P., Strickland, B.R., and Russo, N.F. (1990). Women and depression: Risk factors and treatment issues.

Washington, D.C.: American Psychological Association Press.

Mellman, L., and Bell, R. (1996). Consequences of violence against women. In R. Bell, M. Duncan, J. Eilenberg, M. Fullilove, 

D. Hein, L. Innes, L. Mellman, and P. Panzer, Violence against women in the United States: A comprehensive background paper.

New York, NY: Columbia University, The Commonwealth Fund, Commission on Women’s Health. pp. 31–38.

National Center for Health Statistics. (1993b). Health in the United States and prevention profile. 1992. Hyattsville, MD: 

U.S. Department of Health and Human Services.

Nishizawa, S., Benkelfat, C., Young, S.N., Leyton, M., Mzengeza, S., Montigny, C.D., Blier, P., and Diksic, M. (1997). Differences between males and females in rates of serotonin synthesis in human brain. Proc Nat Acad Sci 94: 5308–5313.

Regier, D.A., Hirschfield, R.M.A., Goodwin, F.K., Burke, J.D. Jr., Lazar, J.B., and Judd, L.L. (1988). The NIMH Depression

Awareness, Recognition, and Treatment Program: Structure, aims and scientific basis. Am J Psychiatry 145:1351–57.

Reisine, S.T. and Fifield, J. 1992. Expanding the definition of disability: Implications for planning, policy, and research. 

Milbank Q 70:491–508

Stoudemire, A., Frank, R., Hedemark, N., Kamlet, M., and Blazer, D. (1986). The economic burden of depression. Gen 

Hosp Psychiatry 8:387–94.

Thurer, S. (1983). Deinstitutionalization and women as caretakers. Hosp Commun Psychiatry 34; (12):1162–63.

Weissman, M.M. (1987). Advances on psychiatric epidemiology: Rates and risks for major depression. Am J Public Health

77:445–51.

Weissman, M.M. (1991). Sex differences and the rates of mental disorders. Paper prepared for the IOM conference on assessing

future needs: Mental and addictive disorders in women, Washington, D.C..

Weissman, M.M. and Klerman, G.L. (1977). Sex differences and the epidemiology of depression. Arch Gen Psychiatry 34:98–111.

Weissman, M.M. and Klerman, G.L. (1992). Depression: Current understanding and changing trends. Ann Rev Public Health

13:319–99.

Wells, K.B., Golding, J.M., and Bumam, M.A. (1988). Psychiatric disorder in a sample of the general population with and 

without chronic medical conditions. Am J Psychiatry 145:976–81.

Wells, K.B., Stewart, A., Hays, R.D., Bumam, A., Rogers, W., Daniels, M., Berry, S., Greenfield, S., and Ware, J. (1989). 

The functioning and well-being of depressed patients: Results from the Medical Outcomes Study. JAMA 262:914–19.

Woods, N.F. (1995) Women and their health. In C.I. Fogel and N.F. Woods (Eds.), Women’s health care: A comprehensive 

handbook. Thousand Oakes, CA: Sage Publications, Inc. pp. 1–22.

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
Raymond L. Woosley, M.D., Ph.D.

Professor and Chair

THE PHARMACOLOGIC DIFFERENCES Department of Pharmacology

BETWEEN WOMEN AND MEN Georgetown University Medical Center

For the most part, the only practical opportunity to critically evaluate potential differences between the

actions of drugs in subsets of the population (in this case women and men) is during a drug’s clinical

development. Once a drug is in general clinical use, only the most dramatic differences in response are

likely to be detected. Until recently, women have been underrepresented in clinical trials during drug development,

and differences in response were not detectable or even anticipated during data analysis. Therefore, few of the

drugs in clinical use today have been carefully examined for differences in response between women and men. 

Yet, as increased awareness of these potential differences has grown, it has become clear that there are major

unforeseen differences in how some drugs are handled (pharmacokinetic differences) and how the body responds 

to drugs (pharmacodynamic differences).

Pharmacokinetic and Pharmacodynamic Differences

Because of advances in analytical chemistry, it has become possible to examine the pharmacokinetics of most

drugs and compare their fate in women and men. These studies can often be performed in normal volunteers and

are far easier to conduct than a clinical trial seeking to measure a surrogate for the drug’s actions or, more difficult

yet, clinical benefit. Therefore, far more pharmacokinetic studies have been performed comparing plasma drug

concentrations in women and men. Relatively few pharmacodynamic comparisons are available. This has become

an important point because one cannot assume that higher or lower plasma concentrations in one sex will always

yield the expected difference in response. The best example is propranolol. Several studies have demonstrated the

higher clearance of propranolol in women and the resulting lower concentrations in plasma. However, our recent

study, funded by the Office of Women’s Health of the FDA, demonstrated that, at the same plasma concentration,

women were more sensitive to propranolol than men, resulting in the same clinical response to a given dose. In

this case, increasing the dosage for women to account for their lower plasma concentration would have been

unnecessary and potentially dangerous.

I will not attempt to summarize the numerous examples of gender differences in pharmacokinetics and drug

response that have been documented in the medical literature. These have been reviewed by Harris, et al. (Drugs,

50(2):222, 1995) and by Dr. Mary Berg (Proceeding: Gender-related Health Issues, 55th World Congress of Pharmacy and Pharmaceutical Sciences, Aug. 29-30, 1995, Stockholm, Sweden, ISBN 0-917-330-80-3). These reviews

cite ample evidence that one of the more relevant pharmacokinetic parameters (absorption, distribution, clearance,

half-life, metabolic or renal clearance, protein binding) may be different for a specific drug when women and men

are compared. What is often missing are data to show that these differences are clinically relevant. It is unlikely

that small, even statistically significant, differences in pharmacokinetics will be clinically relevant. A possible 

exception would be for a drug with a narrow therapeutic index, i.e., the range of dosages required for efficacy are

very near those that cause side effects. There are numerous reasons why such differences in response, even if present, might not be detected. Many drugs (especially those with a narrow therapeutic index) are titrated to a clinical

endpoint, and the differences would only appear as a slightly higher or lower final dosage for women compared 

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66

to men. However, when there is no readily available endpoint for titration (e.g., cancer prevention), a pharmacokinetic difference could mean that women would be less likely to receive an effective dosage. More rapid clearance

and lack of titration were considered as the reason why women with subarachnoid hemorrhage failed to respond 

to the investigational drug trilizad.

Drug Metabolism

Recent advances in our knowledge of drug metabolism have identified fruitful areas of research that have not

as yet addressed the potential importance of gender. The ability to determine the specific isozyme responsible for

oxidative metabolism of drugs by cytochrome P450 (CYP) enzymes has made it possible to predict how drugs are

likely to be metabolized in humans and to predict which drugs are likely to interact. Only a few of the CYP family of

enzymes have been carefully studied for gender differences, but the CPY3A family, which is responsible for metabolism of most drugs, has shown consistently higher activity in females resulting in lower plasma concentrations for

many drugs. Important enzymes, such as CYP2D6 and CYP2C19, which have polymorphically distributed activity,

have not been adequately studied for differences in men and women. Important detoxification enzymes, such as

conjugation, have been found in some studies to have lower activity in women. Fluorouracil dehydrogenation,

responsible for clearance of the anticancer drug 5-fluorouracil, was found to have lower activity in women, raising

concern that they should be given a lower dosage than men. However, a clinical study comparing efficacy at equivalent exposures would be required to be sure that the differences in metabolism justify a change in dosage for this

potential life-saving and, at the same time, potentially toxic drug.

Gender-specific Factors

Numerous studies have demonstrated that sex-specific factors, i.e., menstrual cycle, menopause, pregnancy,

oral contraceptives, and hormone replacement therapy, can be responsible for pharmacokinetic differences between

women and men and within an individual studied at different times. Importantly, there are many studies in the 

literature that have conflicting results, often because they have small sample size or design errors. In many cases,

the mechanism responsible for the influence of menopause lies in the effects of hormones to competitively inhibit

drug metabolism or in some cases to induce the metabolism of drugs.

Gender and Adverse Drug Reactions

Case report: A 29-year-old female was taken to the emergency department because of an episode of syncope.

She had been taking terfendadine (Seldane) for seasonal allergies and her podiatrist had prescribed ketoconazole

(Nizoral) for a fungal infection. Four days later, she was working in the garden and suddenly lost consciousness,

fell to the ground, and then regained consciousness in a few seconds. In the emergency department, the physicians

recorded a negative physical and laboratory evaluation. However, her ECG was later noted to have a QT interval 

of 520 msec (normal <440).

She was discharged and sent home with instructions to return if she had recurrence of her symptoms. The

next day, she was found dead on the floor of her living room holding her 3-month-old infant.

This tragic case is one of several dozen similar reports with terfenadine, a normally very safe antihistamine. 

It is now known that the cause of death in cases such as this and others with astemizole (Hismanal) is most likely 

a form of ventricular tachycardia, torsades de pointes (TdP). TdP is a syndrome in which the arrhythmia has a

A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY
characteristic appearance on the ECG, “twisting of the points,” and is preceded by prolongation of the QT interval.

This arrhythmia has been observed with a broad range of drugs that have as a common feature the ability to block

potassium channels in the heart. These are the channels responsible for repolarization of the action potential and,

when blocked, result in QT interval prolongation on the surface ECG. Although originally described with antiarrhythmic drugs (quinidine, procainamide, disopyramide, sotalol), TdP has also been reported with antihistamines

(terfenadine and astemizole), antibiotics (IV erythromycin, pentamidine, trimethoprim/sulfa, halofantrine), and

pimozide, haloperidol (Haldol), thioridazine (Mellaril), cisapride (Propulsid), bepridil (Vascor), and several 

other drugs.

It has become apparent that the risk of developing TdP with many of these drugs is greater in women than 

in men. For the antiarrhythmic drugs, terfenadine, prenylamine, halofantrine and pimozide, there is a clear preponderance of women in the reports in the literature or in the FDA’s Medwatch database. The mechanism of the

increased risk is not known. It is not explained by higher plasma concentrations in women or other obvious clinical

factors. One possible contributing factor is that women normally have a longer QT interval at baseline than men.

Animal research has shown that the longer QT interval can possibly be explained by effects of sex hormones on 

the expression of potassium channels in the heart. These studies also found that sex hormones can modify the 

sensitivity of the heart to potassium channel blocking drugs, in this case quinidine. Estrogen-treated hearts, when

studied in vitro, were more sensitive to quinidine than hearts previously treated with androgens. The results of

another recently completed clinical study, funded by the Office of Women’s Health at the FDA, has confirmed 

these findings in normal men and women. When given intravenous doses of quinidine, the women had ~50 

percent greater prolongation of their QT interval than the men at any given concentration.

These studies have not yet identified the mechanism for the greater sensitivity of females to potassium 

channel blockers. Additional factors are clearly necessary to explain why some women are especially sensitive 

and develop the clinical arrhythmia. However, understanding the mechanism would have the potential to indicate ways to predict and then prevent the occurrence of this rare, but potentially lethal arrhythmia.

In summary, there are documented differences in the pharmacokinetics and pharmacodynamics for drugs 

in women and men. While many of these are not clinically relevant, some have been found to result in increased

risk of adverse effects, even life-threatening arrhythmias. Research into the mechanism of this and other genderspecific adverse drug reactions is necessary to reduce the unwanted consequences of drug therapy for women 

and may additionally lead to improved therapy for men, children, and the elderly.

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Public Testimony

INTRODUCTION

T O THE PUBLIC

TESTIMONY

on women’s health for the 21st century. Your participation provides us continuing support and inspiration 

for the future improvement of women’s health through

biomedical and behavioral research, and we are very

appreciative of being a part of this process.

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 

to women’s health issues and to establish a science base

that will permit reliable diagnoses and effective treatment and prevention strategies for women through

NIH-supported biomedical and behavioral research. 

The major objectives of our office are:

• 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 national research agenda for NIH for

future directions in women’s health research; 

• To ensure that women are appropriately represented in biomedical and biobehavioral research

studies, especially clinical trials, that are supported by NIH; and

• 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, such as this at which you are 

gathered today.

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

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VOLUME 5

New Orleans, Louisiana 

June 11, 1997

Welcome to the second of three regional public

hearings that the Office of Research on Women’s Health

(ORWH) of the National Institutes of Health (NIH) is

pleased to sponsor, to receive public testimony on the

women’s health research agenda for the 21st century.

We are grateful to our regional hosts, Tulane University Medical Center, Xavier University of Louisiana,

and Meharry Medical College. They have worked so

diligently with us to assist in bringing this facet of NIH’s

fact-finding process on public views of important issues

for research on women’s health to New Orleans. 

In reviewing and renewing our priorities for

women’s health research at NIH, we look to the 

broader community of scientists, health care providers, and women’s health advocates to ensure 

that we have the most up-to-date information about

continuing and emerging concerns that confront

women in preserving their health and well being 

and in overcoming adverse health consequences 

from conditions or diseases that affect them.

Because NIH is the primary agency within 

the Department of Health and Human Services that

performs, promotes, and supports biomedical and

behavioral research, our focus is on research which

should be initiated, expanded, or enhanced through

NIH programs on women’s health, as well as to promote career opportunities for research on women’s

health, especially that of women in biomedical 

careers. Therefore, we are delighted that so many 

of you are here to support our efforts and provide 

your wisdom and insights into our consideration 

of issues of importance for the NIH research agenda 
72

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

From the time of the establishment of ORWH 

and the structuring of our first NIH research agenda 

on women’s health, we have utilized public hearings 

to receive testimony from public representatives, 

and to build upon that testimony through scientific

meetings and workshops to construct priorities for

women’s health research. The report of that first 

undertaking, National Institutes of Health: Opportunities for Research on Women’s Health, is based upon 

public testimony and a scientific meeting held in 

Hunt Valley, Maryland in 1991, and is available 

from the offices of ORWH. 

In September 1996, at our first regional 

meeting in Philadelphia, we began our process 

of re-examining our research agenda to ensure 

that it is relevant as we move towards the next 

century, thus, the name of this series of meetings 

is, “Beyond Hunt Valley: Research on Women’s 

Health for the 21st Century.”

During this scientific workshop in New 

Orleans, we shall examine aspects of the research 

agenda based upon sex and gender differences, 

i.e., physiological, psychosocial, and pharmacologic

differences between women and men. At our third 

and last regional meeting in Santa Fe, New Mexico 

on July 21-23, hosted by the University of New 

Mexico Medical Center and the University of Iowa

School of Pharmacy, we shall focus on factors that 

contribute to differences in health status and health

outcome among different populations of women. 

Finally, on November 17-19, we shall bring

together the results of all three regional meetings 

in a workshop which will be held in Bethesda, 

Maryland, to provide an opportunity for our participants to guide our Task Force in developing 

recommendations for the NIH research agenda 

for the beginning of the 21st century. I invite all 

of you to join us in these further steps.

During today’s Public Hearing, we have 

specifically requested perspectives about:

• The state of knowledge and continuing or 

emerging gaps in knowledge about women’s 

health across the life span;

• Sex and gender differences and their impact 

on women’s health;

• New priorities for research on women’s health;

• Environmental, genetic, hormonal, nonhormonal, and other factors that impact 

on women’s health; and

• Career issues for women scientists and how 

to overcome barriers.

Your testimony will be received and reviewed 

by our Task Force on the NIH Women’s Health

Research Agenda for the 21st Century. We are 

fortunate to have members of the NIH scientific 

community, as well as women’s health advocates, 

scientists, and health professionals from across 

the country who are serving as members of this 

important Task Force. 

We are grateful for the dedicated leadership 

of this Task Force by the cochairs: Dr. Marianne 

Legato, a distinguished cardiologist and women’s 

health researcher and advocate of Columbia University, who is a member of our Federal Advisory 

Committee, and Dr. Donna Dean, Chief, Biological 

and Physiological Sciences, Division of Research 

Grants at NIH, who serves as a member of our 

NIH Coordinating Committee and Chair of our 

NIH Research Subcommittee which provides advice 

to ORWH about priorities and funding programs.

We look forward to your contributions to this

process and thank you for your role in reassessing

women’s health research as we enter the next century.
Gerald S. Berenson, M.D.

Tulane Center for Cardiovascular Health

James E. Dill, M.D.

Behavioral Medicine Solutions of Virginia

Carolyn Evans, M.S.W.

Grace House of New Orleans, Inc.

Wonda L. Fontenot, Ph.D.

Wannamuse Research Institute

Julie E. Goslee, Pharm.D.

Xavier University of Louisiana

Alton E. Hadley

Louisiana Department of Health and Hospitals 

Saletta Holloway

Meharry Medical College

Marlene Keeling, B.S.B.A.

Chemically Associated Neurological Disorders

(CANDO) 

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

Tulane University School of Public Health and 

Tropical Medicine

Marva L. Lewis, Ph.D.

Self

Jennifer C. Lovejoy, Ph.D.

Pennington Biomedical Research Center

Frances Mather, Ph.D.

Tulane University

PUBLIC TESTIMONIES

NEW ORLEANS, LOUISIANA 

JUNE 11, 1997

VOLUME 5

73

Danita M. Muse, M.S.W.

Women With a Vision, Inc.

Marcy Ouellette, M.D., M.P.H., T.M.

Louisiana Office of Public Health

Eileen M. Palace, Ph.D.

The Center for Sexual Health

Tulane University Medical Center

Jayashree Rao, M.D.

Self

Col. Irene Rich

United States Army

Medical Research and Materiel Command

Meghan-Morgan Shannon, M.S.

Medical Professionals with CFIDS/CFS/ME

Amanda Sherman

DES Action USA

Denese O. Shervington, M.D., M.P.H.

Institute of Women and Ethnic Studies
Public testimonY

74

Director

Tulane Center for Cardiovascular Health

Gerald S. Berenson, M.D. New Orleans, Louisiana

Heart disease is the major cause of morbidity and mortality in women and accounts for an unbearable 

cost of medical care in middle-aged and older women in the United States today. Between the years 1979-1981,

Louisiana ranked seventh in the average annual coronary heart disease (CHD) death rate among white women 

and sixth among black women, ages 35 to 74 years. Although the prevalence of early CHD is greater in men, 

the amount of CHD in women after the age of 65 increases significantly; overall, women manifest symptoms of 

cardiovascular disease on the average 10 years later than men. The high morbidity and mortality after menopause,

however, indicate the importance of studying heart disease in women. Diabetes mellitus is particularly severe in

women and promotes CHD at an early age. It is also known that cigarette smoking and inactive lifestyles, highfat and high-sodium diets, and the marked prevalence of obesity, as well as hypertension and dyslipidemia, 

contribute to severe coronary artery disease in relatively young women.

Studies in the Bogalusa Heart Study, a long-term epidemiologic study on children, adolescents, and young

adults, show risk factors can be identified early in life and the major etiologies of heart disease, atherosclerosis,

hypertension, and adult onset diabetes all begin in childhood. Morbidity in young adults 19 to 32 years of age

shows that some 10 percent of white females and 22 percent of black females have a BMI greater than 32.3kg/m2,

representing morbid obesity. Fifteen percent of black females already demonstrate hypertension. Further, risk 

factors tend to cluster with obesity, increased insulin resistance, hypertension, and dyslipidemia. Of particular 

interest, the clustering of cardiovascular risk factors in young adults, Syndrome X, results in a strong relationship

with coronary atherosclerotic lesions found at autopsy. This clustering is associated with an acceleration of coronary atherosclerotic lesions. On an average, atherosclerotic involvement of coronary vessels tends to be less in

young women, but the severity of lesions can be quite extensive in some individuals, predictive of CHD at a 

relatively young age.

Poor lifestyles and behavior in youths include cigarette smoking, sedentary activity, and dietary intake. 

Some 30 percent of high school students are reporting consistent use of tobacco and alcohol. With regard to 

diet, some 80 percent are exceeding the American Heart Association recommendations for total fat and saturated 

fat intake. Decreased physical activity has enhanced a secular trend of increased obesity.

The study of cardiovascular risk factors and lifestyles in children and young adults has serious implications 

for the development of adult CHD, cancer, and osteoporosis. The studies emphasize the need not only to study

females as adults, but to continue investigations of the early onset of chronic diseases as they begin in childhood.

Such observations can help guide more rational methods of prevention.

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

VOLUME 5

75

Endoscopic Ultrasound of Virginia and 

Behavioral Medicine Solutions of Virginia

James E. Dill, M.D., F.A.C.P. Roanoke, Virginia

The Gallbladder, the Gut, and the Brain: Connections and Implications for Women’s Health

My name is Dr. James Dill. I represent Endoscopic Ultrasound of Virginia and Behavioral Medicine Solutions 

of Virginia, both of which are Divisions of Roanoke Gastroenterology, P.C., headquartered in Roanoke, Virginia. 

I am a gastroenterologist in private practice with graduate training in rehabilitation counseling. My interest areas 

are research involving the diagnosis of gallbladder disease with endoscopic ultrasound and the biopsychosocial

aspects of irritable bowel syndrome (IBS). Both of these conditions predominantly affect women.

My goals in testifying are to stimulate interest in new diagnostic and treatment modalities, respectively, 

concerning the above disorders. It is hoped that these diagnostic and treatment methods will be utilized to 

benefit women — relieving suffering through quality, cost-effective health care.

Today, I have the privilege of speaking to you about two medical conditions that are not usually discussed

together, both of which are important to women’s health. The first condition is gallbladder disease of the type 

that is often difficult to diagnose. Our most recent article on this research, “Symptom Resolution or Relief Post

Cholecystectomy Highly Correlated with Combined Endoscopic Ultrasound and Stimulated Biliary Drainage

(EUS/SBD),”1 which has been accepted by the journal Endoscopy, deals with this issue.

Gallbladder disease is common in the general population with the incidence of gallstone disease reported 

to be as high as 10 to 40 percent in women, depending on the age range.2 In the United States, it has been 

estimated that approximately 20 million individuals have gallstones.3

Treatment decisions are straightforward for symptomatic patients having gallstones on transabdominal 

ultrasound (TUS). These decisions are much more difficult in patients with classical biliary pain symptoms 

and negative TUS. Many of these patients, the majority of whom are women, continue with severe bouts of 

abdominal pain and undergo multiple, costly, and at times uncomfortable tests. Worse yet, many are labeled 

as having functional disease and are told that their problems are “all in their head.” Evidence is accumulating 

that significant numbers of patients with biliary symptoms and negative TUS have clinically significant gallbladder disease manifested by gallstones or gallbladder inflammation and possibly cholesterolosis.4–8

Recently, evidence has been accumulating that a new technique, combined endoscopic ultrasound and 

stimulated biliary drainage (EUS/SBD), has the ability to select out symptomatic patients with histologic gallbladder disease not evident on other tests, but more importantly who will benefit from cholescystectomy.7,8

EUS/SBD is performed under sedation by placing an endoscope with an attached ultrasound probe into the 

patient’s stomach — this allows a superior view of the gallbladder and its contents, including tiny stones and

sludge when present. The gallbladder can then be stimulated with an intravenous substance named sincalide 

and bile collected for microscopic examination looking for the presence of crystals. These crystals represent 

the building blocks of gallstones.
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Eighty patients were selected for a study from a group of 81 with biliary pain, negative TUS (except for 

gallbladder sludge on three) and positive EUS/SBD.1 All 81 patients underwent cholecystectomy consecutively. 

One patient was eliminated from the study because multiple attempts to contact her were unsuccessful. Seventyone of the patients were female (89 percent) ages 14 to 82 (average 45); and nine were male (11 percent) ages 23

to 61 (average 44). 

The 80 patients were surveyed an average of 15.4 months post-cholecystectomy with a range of 7 to 27

months. Seventy of the patients were 1 year or more post surgery. Contacts were made by telephone and the

patients were questioned as to the presence or absence of their original biliary pain and the presence or 

absence of improvement in that pain pattern if not resolved.

Cholecystectomy 76 of the 81 original patients had abnormal histopathology of either cholecystitis, 

cholesterolosis, or both. This gave a sensitivity of 93.8 percent and a positive predictive value of 100 percent 

for EUS/SBD. In the outcome study, 70 of the 80 patients (with positive EUS/SBD) for whom data was available (87.5 percent), remain free of biliary pain an average of 15.4 months post-cholecystectomy. The range 

of followup was 7 to 27 months. Seven patients (8.8 percent) remained with biliary pain but were improved. 

These figures gave an overall total of 77 (96.3 percent) patients who were either free of biliary pain or improved. 

Only three (3.7 percent) of the patients were unimproved.

These outcome results are important in that they represent the only lengthy outcome study in a patient 

population this large who were post-cholescystectomy for biliary pain and negative (or nearly negative) TUS, 

but positive EUS/SBD.

In summary, EUS/SBD shows great promise in the detection of subtle gallbladder disease, not evident on 

TUS or other diagnostic tests. Even more importantly, positive EUS/SBD predicts pain relief post-cholecystectomy

in a high percentage of these patients; the overwhelming majority of whom are women.

I have undertaken a preliminary study of the relationship between gallbladder disease and IBS.9 The charts 

of 20 patients who had been diagnosed by EUS/SBD and who had been proven to have gallbladder disease at

surgery were reviewed. Ten of the patients had a diagnosis of IBS and 19 had gastroesophageal reflux disease

(which is considered part of the spectrum of IBS). This is consistent with the finding that many of our gallbladder patients had poor motility of the gallbladder suggesting a global motor disorder.

Next, I would like to discuss IBS further, specifically our paper “Abuse, Threat and Irritable Bowel Syndrome:

What is the Connection?” which has been accepted for publication in Gastroenterology Nursing.

10

IBS continues to claim the attention of clinicians and researchers alike as the mysteries of the “brain-gut 

connection” are unveiled. Drossman and others have led us to fully understand that chronic functional abdominal

pain, including IBS, is best viewed from a biopsychosocial framework.11 Nurses who have had daily experience

working with patients with IBS know firsthand the degree of suffering, shame, and disability that can accompany 

a diagnosis of severe IBS.

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Several years ago we, as a physician and a nurse in a solo gastroenterology practice, targeted the patient 

with IBS for extra attention and support and developed an integrated treatment model which proved to be helpful to patients.12 This collaborative practice approach involving physician, nurse, and counselor enabled us to 

focus on the psychosocial aspects of care instead of symptoms alone. That same year researchers labeled IBS 

as a multi-billion dollar problem and proved what we had long suspected; the enormity of the cost to society.13

There is increasing awareness in the medical community of the association of interpersonal abuse and 

functional bowel disorders including IBS. Our research study was designed to determine the percentage of 

patients with both IBS and histories of sexual abuse in a solo gastroenterology practice, as well as the effects 

of that abuse and threat on symptom severity.

The sample consisted of 77 consecutive patients attending routine outpatient appointments in a solo 

gastroenterology practice. Each patient had been previously diagnosed with IBS using Manning criteria14 after 

a gastroenterological workup to rule out organic disease.13 Patients ranged from 24 to 84 years with a mean 

of 53.7 (SD = 14.1). Seventy-nine percent were female; 94 percent of the subjects were white, 1.4 percent 

were African-American; 2.9 percent were Hispanic; and 1.4 percent were American Indian.

After signing voluntary consent forms, the patients were administered a questionnaire packet, in a private 

setting, consisting of various measures. The instruments included a demographics questionnaire, a modified 

IBS symptom checklist,15 and a modified version of the Sexual Abuse History Inventory.16

Thirty-eight percent of the patients reported histories of childhood or adult sexual abuse. Patients with 

histories of abuse alone had a mean symptom score similar to those without such histories (32.5 vs. 30.5). 

Patients reporting abuse plus threat of abuse had a significantly higher mean symptom score (44.1) than 

patients reporting no abuse (30.5).

The study results confirm the idea that threat combined with abuse is a more significant predictor of 

IBS symptomology than abuse alone (when both are compared with no abuse) even after accounting for socioeconomic status and other variables. The results of this study raise some important considerations. The first 

point is that of demographics: namely that 38.5 percent of the study population had a history of childhood 

or adult sexual abuse which is greater than the 30 percent figure reported by Talley19 for a general population 

with IBS who were surveyed by mailed questionnaire. However, the percentage in our study is less than the 

44 percent reported by Drossman18 in a tertiary care academic setting.

Another point of interest in this study was the finding that 68 percent of the patients with histories of 

childhood or adult sexual abuse reported that they were also exposed to the threat of abuse. Patients exposed 

to both threat and actual abuse had much higher symptom scores (mean 44.1) than those not exposed to abuse

(mean 30.5). This raises the possibility that abuse is more likely to affect symptom severity when combined 

with the threat of abuse.
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This important connection between threat, stress, and gut response is underlined by the recent study of 

Silverman, et al., that demonstrated a brain activation pattern, involving the central vigilance network, that 

was abnormal by positron emission tomography in subjects with IBS.20

Individuals who develop posttraumatic stress disorder (PTSD) are hypervigilant and quite sensitive to 

perceived threats in their environment.20 This factor, combined with the tendency to activate the cerebral 

vigilance network in patients with IBS as mentioned above, has particular clinical relevance in dealing with 

patients with IBS who have been abused. The establishment of a “safe” therapeutic environment, involving 

primarily the relationships between key office personnel and patients, is paramount. We have developed an 

integrated treatment model21 which deals directly with the issue of safety in the clinical setting. In this model 

the RN functions as a “bridge” between the physician and counselor, facilitating mental health referral through

reimbursable nurse visits. This is possible when the RN genuinely demonstrates such characteristics as empathy

and kindness toward these patients with special needs in an environment created to be as nonthreatening as 

possible (i.e., draping equipment, attuning to background noise).21

An additional unifying factor between IBS, abuse, and gallbladder disease is suggested by the research 

of Stuppy who found deposits of met-endkephalin in the cholesterolosis of gallbladders of certain patients 

with panic disorder.22 These patients had been exposed to chronic, inescapable stress and had developed 

not only panic disorder, but gallbladder disease as well. This connection is worthy of further study.

In conclusion, I would like to challenge the medical profession to heed the needs of patients with the 

conditions I have discussed. Physicians in particular must become more sensitive to the issues these predominantly female patients represent. Now is the time to respond!

References

1 Dill, J. Symptom Resolution or Relief Post Cholecystectomy, Highly Correlated with Positive Combined Endoscopic 

Ultrasound and Stimulated Biliary Drainage (EUS/SBD); Accepted for publication in Endoscopy.

2 Sleisenger, M. and Fordtran, J. Epidemiology, Pathogenesis Natural History, and Medical Therapy of Gallstones; 

Gastrointestinal Disease Vol. 2 (1993):1789.

3 Yamada, T., Alpers, D., Owyang, C., et al. Textbook of Gastroenterology Vol II (1995): 2187.

4 Dahan, P., Amouyal, P., et al. Is endoscopic ultrasonography (EUS) helpful in patients with suspicion of complicated 

gallstones and normal ultrasonography (US)? AGA Abstracts, April 1993.

5 Amouyal, G. and Amouyal, P. Endoscopic ultrasonography in gallbladder stones; Gastrointestinal Endoscopy Clinics 

of North America Vol 5; No 4, October 1995, P 825–30.

6 Dill, J. Comparative Accuracy of Endoscopic Ultrasound, Transabdominal Ultrasound and Biliary Drainage in the 

Diagnosis of Cholecystitis; Abstract Gastroenterology 108 (1995): 414.

7 Dill, J., Hill, S., Callis, J., et al. Combined Endoscopic Ultrasound and Stimulated Biliary Drainage in Cholecystitis 

and Microlithiasis — Diagnoses and Outcomes; Endoscopy (1995): 27.

8 Dill, J. Twenty-Three Month Experience with Combined Endoscopic Ultrasound and Stimulated Biliary Drainage in 

the Preoperative Diagnosis of Subtle Cholecystitis and Cholesterolosis; Abstract; Gastrointestinal Endoscopy, Vol 43, 

No 4 (1996): 418: Poster Presentation; ASGE, Digestive Disease Week (DDW), San Francisco, Calif. May 1996.

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9 Dill, J. Cholecystitis associated with gastrointestinal motor disorders. Am J Gastroenterol 90 (1995): 192.

10 Dill, B., Sibey, G.A., Dill, J.E., and Brende, J.O. (1997) Abuse, Threat, and Irritable Bowel Syndrome. What is the 

Connection? Accepted for publication Gastroenterology Nursing.

11 Drossman, D.A. Chronic functional abdominal pain. American Journal of Gastroenterology 91 (11) (1996): 2270–81.

12 Dill, B. and Dill, J.E. The R.N.’s role in the office treatment of irritable bowel syndrome. Gastroenterology Nursing 18 

(3) (1995): 100–103.

13 Talley, N.J., Gabriel, S.E., Harmsen, W.S., Zinmeister, A.R., and Evans, R.S. Medical costs in community subjects 

with irritable bowel syndrome, Gastroenterology 109 (6) (1995): 1736–41.

14 Manning, A.P., Thompson, W.G., Heaton, K.W., and Morris, A.F. Towards positive diagnosis of the irritable bowel. 

British Medical Journal 2 (1978): 653–54.

15 Drossman, D.A., Sandler, R.S., McKee, D.C., and Lovitz, A.J. Bowel Patterns among subjects not seeking health care: 

Use of a questionnaire to identify a population with bowel dysfunction. Gastroenterology 83 (1982): 529–34.

16 Badgley, R., Allard, H., McCormick, N., Proudfood, P., Fortin, D., Oglive, D., Et al. Occurrence in the population. 

In: Sexual offenses against children. Ottawa: Canadian Government Publishing Centre, (1) (1984): 175–93.

17 Talley, N.J., Helgeson, S., and Zinsmeister, A.R. Are sexual and physical abuse linked to functional gastrointestional 

disorders? (Abstract) Gastroenterology 102 (1992): A52.

18 Drossman, D.A., Leserman, J., Nachman, G., Li, Z., Gluck, H., Toomey, T.C., and Mitchell, C.M. Sexual and physical abuse

in women with functional or organic gastrointestinal disorders. Annals of Internal Medicine 113 (11) (1990): 828–33.

19 Silverman, D.H.S., Munakata, J.A., Ennes, H., Maudelkern, M.A., Hoh, C.K., and Mayer, E.A. Regional cerebral activity 

in normal and pathological perception of visceral pain. Gastroenterology 112 (1) (1997): 64–72.

20 Brown, P. and Yantis, J. Personal space intrusion and PTSD. Journal of Psychosocial Nursing 34 (7) (1996): 23–28.

21 Dill, B., Dill, J.E., Sibey, G.A., and Brende, J.O. The R.N.’s role in the office treatment of patients with histories 

of abuse: A proposed treatment model. Accepted for publication by Gastroenterology Nursing, 1997.

22 Stuppy, W.F. Demonstration of gross deposits of endogenous opiod in the gallbladder and duodenal mucosa of patients 

with panic disorder. American Journal of Gastroenterology 90 (1995): 1666.

Grace House of New Orleans, Inc.

Carolyn Evans New Orleans, Louisiana

The unique needs of women in substance abuse treatment are not addressed in most traditional substance abuse treatment programs which are based on male norms. Often such treatment programs are not 

only ineffective for women, but can actually result in victimization. A holistic treatment model — addressing 

the physical, emotional, spiritual, and sociological needs of women — is indicated for safe and effective treatment for female substance abusers. Negative factors for women in currently used treatment modalities are 

explored along with a model program for gender-specific substance abuse treatment.

Indications for future research needs in gender-specific substance abuse treatment for women are explored.
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Wannamuse Research Institute

Wonda L. Fontenot, Ph.D. Opelousas, Louisiana

This testimony is concerned with the need and relevance of applied research in relation to behavioral 

health issues of rural women, especially rural African-American women. An equally important concern is how 

these behavioral issues impact access and quality care for women, as well as the adoption of preventive health 

care measures. In my testimony, I will call attention to health concerns affecting the health status of women 

based on cultural factors, socioeconomic conditions, and issues of race and gender.

Cultural beliefs and practices associated with causes and treatment of illness, and other lifestyle behaviors, 

are important determinants of health status, and in the prevention of morbidity and mortality. The lack of cultural sensitivity on the part of health care providers toward the rural recipient, remains an issue in rural communities, and continues to threaten the cost of effective health care, and contributes to a higher risk of poor 

health among women.

Issues of gender in rural society is also relevant, as often times medical diagnosis and treatment for women 

is based on the status of women in society. Thus, more research is needed to improve the quality of health care 

for women, and to fully understand the impact these variables have on the well being of women who are rural,

poor, and/or African American.

Assistant Professor of Clinical Pharmacy

Xavier University of Louisiana 

Julie E. Goslee, Pharm.D. New Orleans, Louisiana

Gender Differences in Prescribing Postmenopausal Hormonal Replacement Therapy

A growing number of women are living longer (up to one-third of their lives) after their reproductive years,

and physicians and pharmacists find themselves increasingly needing to intelligently discuss the issue of hormone

replacement therapy (HRT). Concerns such as “How will HRT help me?” “How will it hurt me?” “Is it right for me?”

and “How do I take it?” are often asked of both the physician and the pharmacist.

Our understanding of the benefits of HRT has expanded greatly in the last 5 years. Effects of HRT can be 

measured in the potential for lives saved or lost, but it also may improve many harder to measure quality-of-life

factors. Postmenopausal hormone replacement therapy has been shown to be cost effective in decreasing morbidity and overall mortality in users, especially with long-term use.

So then, why are only 3 to 15 percent of eligible women receiving HRT? This may be partially due to 

uncertainty regarding the risks versus the benefits of HRT. Strong scientific evidence that HRT may decrease 

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the incidence of hot flashes, urogenital atrophy, incontinence, osteoporosis, and cardiovascular disease is tempered by uncertainty regarding its effects on the risks of stroke and breast cancer. While the infrequent usage of

HRT may be related to these risks, other factors may also contribute to its pattern of use. Research of physician

behavior indicates that practice patterns differ between female and male physicians suggesting that physicianspecific factors may influence the decision to perform particular tests or to prescribe certain medications.

Patients seen by female physicians are more that five times as likely to begin ERT than those seen by male

physicians according to Seto, et al. (J Gen Intern Med 11 (1996): 197–203). These gender differences are also 

seen with cancer screening rates; female physicians perform more cancer screening tests for female patients 

than do male physicians.

After reading this study (and to my knowledge, Seto, et al. were the first to report on the impact of physician

gender on the prescription of ERT in actual clinical practice), I wondered if these same differences could be seen 

in the pharmacy profession. Very often, the pharmacist is consulted by the patient for answers to questions about

their medications; and could there be differences in the knowledge and attitudes about ERT/HRT between male 

and female pharmacists?

Further research is required to determine if these differences reflect differences between male and female 

physicians and pharmacists in knowledge or attitude about ERT/HRT, or gender-specific differences in how 

physicians and pharmacists discuss ERT/HRT with their patients.

About the Organization

Within the mission of Xavier University of Louisiana, the College of Pharmacy is dedicated to develop 

pharmacists who are competent to deliver pharmaceutical care as required in a dynamic health care environment; to serve the profession and community by providing contemporary, innovative, and quality patientcentered health care; and to acquire and disseminate new knowledge through collaborative research.

Office of Alcohol and Drug Abuse

Louisiana Department of Health and Hospitals

Alton E. Hadley Baton Rouge, Louisiana

Barriers for Women in Alcohol and Drug Abuse Treatment

Women have made great strides in gaining equality in the workplace and power in the political arena. 

Society’s view of women and alcoholism and drug addiction has not made similar strides. One assumption 

is that the alcoholic or drug-addicted woman is promiscuous. Another assumption is that she has failed as 

a wife and mother.
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Disapproval of female intoxication has been prevalent in Western societies throughout history. This can be

attributed to two major concerns according to Gomberg: Western man’s concern for female sexual virtue and for

spouse/mother roles. Alcohol is believed to cause women to lose sexual control and engage in immoral behavior.

Any level of intoxication could result in loss of sexual inhibitions or result in an inability to fend off sexual

advances. Women’s roles throughout history have demanded more consistent attention than male roles. Child,

Barry, and Bacon (1965) reason that the temporary incapacity of a woman is more threatening than the temporary incapacity of a man because the care of a field can be abandoned for a day, but the care of a child cannot.

With society’s harsh view of women’s drinking and drug use, women have hidden their problems more 

successfully than men. This has resulted in far fewer women receiving treatment and when they do receive 

treatment the disease has often progressed much further and is more difficult to treat. Many men enter treatment as a result of contact with the legal system or as a requirement of his employer. Women have far fewer 

contacts with the legal system and are not as represented in business and industry as men. Women are often

employed in lower-paying positions and do not have access to employee assistance programs which are instrumental in providing referral services to treatment.

Female alcoholics now account for approximately one-third of the total number of alcoholics. In the 

United States there are about 5 million alcoholic women. Women who are separated, divorced, or single are 

more likely to drink more heavily than married or widowed women, although wives of alcoholics have a high 

rate of drinking problems. 

Alcohol has a more severe physical impact on women. Both sexes experience severe physical problems 

associated with alcohol abuse but the effects are more profound on women after a shorter period of abusive 

drinking and with less alcohol intake. Female alcoholics have a 50 to 100 percent higher death rate than those 

of the male alcoholic. Alcoholic women lose an average of 15 years in life expectancy as a result of cirrhosis, 

circulatory disorders, suicide, homicide, and accidents. Women tend to develop alcoholic hepatitis and cirrhosis 

after much shorter periods of heavy drinking and at lower levels of daily consumption.

Women are generally smaller than men, therefore, if a physically smaller woman drinks the same amount 

of alcohol as a larger man, the woman will have a higher blood alcohol content. In addition, women have less 

body water which would make the blood alcohol content even higher.

A report in the New England Journal of Medicine in 1990 of a study by Frezza found that after consuming 

comparable amounts of alcohol, women have higher blood alcohol concentrations than men, even when allowances for difference in size are calculated. Women are also more suspectable to alcoholic liver disease. The results 

indicated that the bioavailability of alcoholic is much greater in women than in men because women have less 

gastric first-pass metabolism of alcohol.

Alcohol and drugs consumed during pregnancy can have devastating effects on the fetus. Women who 

consume alcohol while pregnant put their babies at risk for fetal alcohol syndrome (FAS) and fetal alcohol effects

(FAE). FAS is one of the major contributors of mental retardation today and elimination of alcohol consumption 

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is the leading preventable cause of mental retardation. The fetus is not capable of efficiently processing alcohol

which it receives from the mother through the placenta. Symptoms of FAS include mental retardation, physical

deformities especially in the facial area, retarded growth, organ malformation, central nervous system dysfunction,

and emotional and behavioral problems. There has been no determination of what a safe amount of alcohol consumption would be for a pregnant woman.

Barriers to effective treatment of women include lack of child care for dependent children, unwillingness of

family members to acknowledge a problem exists, treatment programs designed by men for men, and the added

burden of sexual and physical abuse endured by a high percentage of women clients. Additional barriers include

the need for detox beds for women with their children, lack of medical coverage, dual diagnosis beds for women

with children, and medical conditions needing attention prior to treatment. 

Women who need alcohol/drug abuse treatment and have dependent children have far fewer treatment 

options available to them. These women need services to help them to arrange appropriate child care or should

have treatment centers available that allow the client to bring her children with her to the treatment center.

Family members are often reluctant to confront the female alcoholic especially if she does not match 

the stereotype such as being promiscuous, unkempt, and detached. Some of the alcoholic women in a study 

by Smith (1986) described resistance by their husbands, and even their primary care physicians, to engage in

enabling the woman alcoholic to obtain treatment. These women relied on their own self diagnosis of alcoholism in order to obtain treatment. Greater public education of signs and symptoms of alcohol abuse by women,

especially those that counter current stereotypes, may decrease the extent of denial by family members.

Traditional alcohol and drug abuse treatment was designed to treat the male alcoholic and addict. 

Women respond well to treatment, especially when their special needs receive attention from the treatment 

staff. Treatment facilities should provide services, such as child care, and all female groups should be led by 

female counselors. Groups containing only women provide the members a safe environment to discuss issues 

that they would be hesitant to discuss in the presence of men. It is becoming more apparent that a large 

percentage of addicted women have been sexually and/or physically abused. Female groups provide a safe 

environment for the newly sober woman to discuss feelings and issues that they could not discuss with 

men in the group.

Doshan and Bursch recommended several treatment components that should be included in an effective 

treatment program for women. Group therapy should be the primary mode of treatment; the group should be

made up of women only, including the therapist. The treatment program should contain an assertiveness training component as many alcoholics lack effective interpersonal skills. This training should enable the patient to

increase her ability to express personal rights and feelings and to improve effective communication and interpersonal problem solving.

Social skills training and socialization activities are an important component to include in treatment due 

to the tendency for alcoholic and/or addicted women to isolate themselves. In order to stay sober, addicts must

often abandon old user friends and develop new friends.
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Child care issues must be addressed. Some treatment facilities allow the patient to bring dependent 

children to treatment with them. Treatment includes parent training and counseling directed at helping the 

client deal with guilt about not fulfilling the mother role as they and society expect. In many instances, the 

children of addicted women in treatment are also in need of services due to physical and emotional neglect 

and/or abuse by the mother. A resource for treatment of the children must be considered if the cycle of 

addiction is to be broken.

The following recognizable health-related issues were reported among our state-operated facilities 

for women:

• Gastrointestinal problems • Insomnia

• Respiratory problems • Sexually transmitted diseases

• Dermatological problems • High blood pressure

• Eye Infections • Seizure disorders

• Dental problems • Controlled diabetes

• Urinary tract infections

Several medical concerns are cited as barriers to women seeking treatment including very-high-risk 

pregnancy, uncontrolled seizure disorders, and any problem that absolutely requires medication with abuse 

potential such as benzodiazepines, sedative-hypnotics, narcotic and opioid analgesics, and some skeletal muscle 

relaxants (i.e., SOMA).

The single most common medical problem that interferes with clients in treatment, other than antibiotics, is

the need for dental care. A history of neglectful dental hygiene is common in substance-abusing clients. Once in

treatment, toothaches and dental abscesses can be severe and some facilities do not have dental services available.

Clients usually have no resources to access private dental care. 

In summary, we advocate the following recommendations:

• Education and outreach services need to be available to more women and their families in order to provide

information on risks and the preventive steps that should be taken to avoid or reduce addiction to alcohol

and/or drugs.

• Medical professionals need to be adequately trained in the alcohol and drug abuse field, so that they can 

recognize and better counsel women on prevention and treatment needs.

• Research projects with a focus on the needs of women need to be expanded.

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Council Woman, 29th District

Meharry Medical College 

Saletta A. Holloway Nashville, Tennessee 

Health care is influenced by several factors, including the medical needs of patients, the environment for

research, and major socioeconomic trends. Other important parameters are the societal expectations for health 

care delivery. Besides being familiar with the health care environment, I am a Council woman for the 29th District.

In that capacity, I come in contact with people in my community who have different expectations about health 

care delivery and biomedical research. I can summarize those concerns as follows:

• Health literacy. Consumers need to understand the enormous amount of information about technological

advances and health care delivery systems.

• The concept of disease. Public perception of disease is changing. People now understand that diseases can 

be caused and aggravated by many factors, including biological and socioeconomic factors. Also, there is 

a shift in focus from acute to chronic disorders.

• The need for health promotion and disease prevention.

• Management of disease. The public understands the need for a comprehensive delivery of health care, 

which takes into account their specific disease and individual needs.

• Health care cost. Emphasis has been given to the cost of hospitalizations, physician payments, and 

diagnostic tests, while ignoring the high cost derived from lack of prevention, lack of access to health 

care, and lack of knowledge about health. Preventive medicine should be introduced as one of the 

elements which contribute to contain and rationalize health care cost.

• Research focus. Few people benefit from technological breakthroughs, while a high number of our 

citizens lack access to elemental health care. The public is recognizing that the health of our population 

in general is as important as the health of individuals. While we recognize the value of genetic engineering, we also clamor for a broadening of the base of research areas to find answers on the impact that 

socioeconomics have on the health of our citizens.

• Inclusion of women and minorities in research. The public celebrates legislation mandating the inclusion 

of women and minorities in biomedical research. While the legislative mandate is clear, poor women and

minorities are not participating in biomedical research.

I respectfully make the following suggestions to the National Institutes of Health:

• Develop policies for health promotion and disease prevention.

• Promote research which has an emphasis on population-care management and focus on specific groups 

such as women, minorities, and pediatric and elderly populations.
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• Design strategies and policies to promote the development of women scientists.

• Promote research which looks at disease-management approaches based on clinical as well as 

socioeconomic factors.

• Promote research which finds approaches to manage diseases through early intervention and 

prevention of exacerbations. Technologies should be used to educate patients, physicians, and 

health care organizations, rationalize the use of medications, and modify the environment.

• Promote research on how to obtain and manipulate health data from specific populations. 

Develop the resources and the technology to pull data together and apply it.

• Promote research that looks at quality of care and quality of life throughout the life span.

• Sponsor programs to assist research subjects who can not afford to participate in research trials.

• Make the necessary budgetary allocations to increase the visibility and productivity of women’s 

programs at the National Institutes of Health, including those efforts related to the inclusion and 

retention of women in biomedical research. Special attention should be given to the Office of 

Research on Women’s Health.

• Promote large clinical trials which look at unknown causes of disease and have clear clinical endpoints, 

such as the Women’s Health Initiative.

• Find innovative and effective ways to facilitate the involvement of the public in defining the research 

agenda for this nation. 

Chemically Associated Neurological Disorders (CANDO)

Marlene Keeling, B.S.B.A. Houston, Texas

Research on Women’s Health for the 21st Century Needs to Include Chemicals Implanted in the Body 

When breast implants are removed, they are labeled biohazardous or poisonous. Women have been experimented on for the last 30 years. FDA has never approved a single breast implant. Now is the time to stop the

experiment and do the research before one more woman’s health, and that of her children born after implants, 

is destroyed by the toxic effects of silicone and silica. Secret Scandinavian research in the 1970s revealed that 

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2,6-cis-D, which is very similar to D-4 found in breast implants, had estrogen-like activity, caused atrophy of 

male sexual organs, caused abnormal motility and eventual sperm death, caused stimulation of endometrial 

growth, and definitely passed the placental barrier in pregnant mice. We know more about the fetal effects of

Tylenol than we know about the effects of silicone/silica. Every child deserves to be born free of toxic chemicals. 

Is it possible that in this advanced technological age, we are poisoning ourselves and our future generations. 

I recently coordinated a data gathering of 100 breast implanted women from different support groups 

around the United States which revealed the following: 68 percent had been diagnosed after implantation 

with peripheral neuropathy; 36 percent, demyelinating neuropathy; 70 percent, atypical neurological disease; 

42 percent, organic brain syndrome (loss of cognitive function); 52 percent, lupus or lupus like; 87 percent,

fibromyalgia; 78 percent, atypical connective tissue disease; 39 percent, mixed connective tissue; 12 percent, 

scleroderma; 55 percent, esophageal reflux; 63 percent, gastrointestinal dismotility; 95 percent, chronic fatigue; 

and 47 percent, Sjögren’s syndrome. While I have not had any training in epidemiology and there may be some

bias in that women attending support group meetings may be having more problems with their health, I have

trained myself to be a better consumer by reading peer-reviewed research articles and believe these numbers 

reflect a growing health crisis in this country. The average age of these women was 51 years.

No one seems to be focusing on the neurological part of the toxic effects of silicone/silica. Women with

implants are being diagnosed with reduced blood flow to the brain and loss of cognitive function (it appears 

to be an adult form of attention deficit disorder). Many former hard working, productive women with implants 

are now disabled, without insurance, and unable to take care of themselves or their families. This health care 

crisis grows daily, while the manufacturers would try to blame it on anything but the implants. 

Is it possible that silicone or silica is a lipid-soluble neurotoxin? Over 1,300 peer-reviewed research articles

indicate the harmful effects of silicone/silica in the body. The NIH-sponsored panel concluded on April 17, 1997,

that there does appear to be a connection between silicone breast implants and atypical rheumatic disease. 

Clinical studies are now needed to verify what implanted women have known for some time — something 

has gone disastrously wrong.

According to the Robert Wood Johnson Foundation, 99 million Americans suffer from chronic ailments 

which cost $470 billion a year in direct health costs. And, indirectly, they cost $234 billion in lost productivity

from those who are disabled or die prematurely. Only 26 percent of people with chronic conditions are 65 or 

older. It is time to spend our research dollars on preventative investigations into possible causes of disease 

and remove harmful non-life-saving devices from the market.
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Professor and Chair

Tulane University School of Public Health and Tropical Medicine

Judith H. LaRosa, Ph.D., R.N. New Orleans, Louisiana

The Cause for Enhanced Behavioral Research

As a result of the tremendous focus on biomedical research and dissemination of the findings, Americans 

and their health care providers have access to vast quantities of health information. These data enable us to 

prevent, identify, and control disease. Many live longer and better. However, a substantial number of individuals 

do not act, or act haphazardly, on such life-saving information.

Of particular interest is why women, who compared to men are by far the more dedicated seekers of 

health care, are so resistant to life-preserving change? Why do young women persist in smoking and engage 

in unprotected sex? Why do older women resist mammograms and Pap smears? Why are younger female 

physicians more likely to prescribe preventive services than older male and female physicians? Is the health 

professional community sending the wrong messages? Are the messages too much the “one-size-fits-all” 

approach? Does the media with its “latest medical news report” confuse?

We need to examine the differences in the sexes in response to health information and action. We need to

determine how to reduce barriers and enable women to act in their own best interests. Learning is not a one-way

street from health care professional to patient. Learning is a multifaceted collaboration among women and their

health care professionals to protect and enhance the health of the individual. This is especially important now 

when health care is changing and professional time with patients is being reduced. Behavior change requires 

understanding, time, and commitment by many forces from the individual and her physician to the media.

I urge the following action for NIH and all research institutions dedicated to health promotion and disease:

• Recognize and accept that differences exist among individuals and between women and men. Recognize 

that individuals have different ways of learning and adopting behavior change.

• Allot sufficient funds to support behavioral research and make it a priority across the myriad of diseases, 

disorders, and conditions which affect women — and men. Without such research we cannot successfully

apply and have individuals adopt the health preserving findings.

• Integrate behavioral research into as many clinical studies as possible.

Indeed, a great deal of the information is often already there. It simply needs to be identified and utilized.

This is not a plea to rob basic or applied sciences of their critical role or funds in biomedical research. 

This is an urgent request to acknowledge and stimulate the critical role behavioral research has in biomedical

research. Behavioral research is important for it enables us to effectively use the continually emerging research

knowledge as individuals and as a nation.

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Assistant Professor

Tulane University School of Social Work

Marva L. Lewis, Ph.D. New Orleans, Louisiana

Little research focuses on the role of culture and ethnicity as normative processes that permeate the mental

health and well being of the lives of women and girls. For example, there are some cultural practices and strong

ethnic identity that may be sources of strength as well as sources of vulnerability for women and girls, in view 

of the current public health crisis of interpersonal violence. We do not understand the mental health needs of

women and girls who are the victims, mothers, sisters, girlfriends, and daughters of the epidemic of homicide 

that has defined urban settings in the 90s. What will our psychological legacy be for the next generation of 

children who will be parented and socialized by mothers with experiences of unresolved grief and loss?

In the current research I am conducting with funding provided by the National Institute for Mental Health, 

I am investigating how the task of hair combing may serve as a naturalistic paradigm for research to understand 

the dynamics of African-American mother-daughter relationships. The hair-combing task offers an opportunity 

to compare and contrast the quality of interactions that occur in this observational context with the interactions

that occur in traditional contexts of assessment such as free play and teaching tasks.

Developmental theories of attachment, self-conception formation, and racial socialization provide a conceptual framework for understanding the significance of hair combing interactions (HCI) and the basis for the design

of the study. Intense emotions are associated with hair. The critical nature of skin-to-skin human touch has long

been established and more recently, the importance of parent-to-child nurturing touch to enhance the development of secure attachment relationships. During HCI, mothers must repeatedly touch, pat, and smooth the hair 

of the child. Consequently, the functional aspects of HCI offer an opportunity for attachment as well as intimacy.

The interactions that occur between mothers and their daughters during the task of hair combing may 

contribute in important ways to the infant girls developing a sense of self and may reflect stable attributes of 

the relationship and the mother’s general parenting style. HCI, as a method of assessment, also offers a potential

window for understanding the sociocultural domains of African-American girls’ emerging sense of gender and 

racial self-concept formation. In data from pilot studies I have completed with diverse samples of AfricanAmerican women and girls in three different cities, I found it was possible to rate a variety of discrete 

maternal and child behaviors from videotapes of the interaction.

This study is a descriptive and exploratory study of a low-risk, non-clinical sample of African-American 

mothers, aged 20 and older with daughters aged 20 to 36 months. The specific research questions this study

addresses are: Does African-American mother-daughter interaction look the same in three observational contexts

(free play, teaching, and hair combing)? Is the mother’s ethnicity the best predictor of specific behaviors in hair

combing context? The relationship variables of interest are the mother’s emotional availability; the child’s affect 

and level of compliance with the mother and the overall connectedness and exchange of affect between the 

mother and the child. Each of these behaviors will be analyzed from videotaped interactions in each of the 

three contexts.
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There is a conceptual gap in the research about specifics of the role of culture in the mental health of 

African-American women and girls. The American Psychological Association and ethical standards committee 

of the Council of Social Work Education have both recommended that race and ethnicity be considered in the 

construction and methodology of research studies. It is time to move beyond simple inclusion of descriptions 

of the race and ethnicity of study participants. Cultural heritage and traditions must be the beginning point for

conceptualization, design, and interpretation of research conducted on women and girls. I have provided a brief

example of my research where a cultural conceptualization of the mother-child relationship led to the selection 

of the hair-combing task as a valid method of research.

In conclusion, I recommend the following actions:

• That funding priority be given to the development of an annotated bibliography that brings together 

the existing research that examines culture and mental health of women and girls.

• Researchers, clinicians, students, and educators be provided with continuing education in the form of 

workshops that help them understand the differences between the concept of culture, race, and ethnicity. 

In our current context of our collective weariness over the battle for affirmative action, our reactivity and 

fear of discussions of racism, and ethnic relations, the topic of culture becomes subsumed and typically lost. 

If culture is going to be substantively explored, there must first be a clear understanding of the construct.

• There is need for collaboration and interdisciplinary focus in order to substantively address the issue of 

the role of culture as a source of protection and vulnerability in the lives of African-American women. 

• Basic research on African-American cultural traditions and practices related to women’s roles need to be 

made a priority with funding priorities given to studies that describe the meaning of culture in order to 

build theory and hypothesis about African-American culture.

Chief, Women’s Health Research Program

Pennington Biomedical Research Center

Louisiana State University

Jennifer C. Lovejoy, Ph.D. Baton Rouge, Louisiana

The mission of the Pennington Biomedical Research Center (PBRC) at Louisiana State University is 

promotion of healthier lives through research in nutrition and preventive medicine. As part of this mission, 

PBRC is committed to research in women’s health issues, many of which have a nutritional component. 

The Pennington Center was created by a gift of over $125 million by Baton Rouge oilman and philanthropist C.B. “Doc” Pennington. Its mission is to improve the health of humankind through research in 

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nutrition and preventive medicine. With an operating budget of $17 million for 1996-97, the PBRC 

conducts basic, clinical, and applied research in the following major program areas: obesity, diabetes and 

metabolism, nutritional neuroscience, diet and heart disease, and nutrition and health promotion. 

At the Public Hearing on Issues in Women’s Health Research, women’s health issues will be discussed 

broadly. PBRC brings a unique perspective to this topic in the special area of nutrition and preventive medicine 

and we will use this perspective to highlight aspects of the broad field of women’s health research. We have 

chosen “Nutrition and Women’s Health Across the Life Cycle” as the theme for PBRC’s statement because 

nutritional issues, such as obesity and eating disorders, have major implications for the nation’s health; there 

are important gender differences in the prevalence of these health problems. Furthermore, as in many other 

areas of clinical research, women have been understudied with regard to the relationships between nutrition 

and chronic disease, and there is much to be learned about the physiological responses of women to 

nutritional changes.

Nutritional Factors and Women’s Life Cycle

Because of the influence of reproductive hormones, as well as a number of psychosocial factors, there are 

several periods during a woman’s life when she may be at greater risk for developing a nutrition-related disorder.

These times include adolescence, when eating disorders typically appear, and pregnancy and menopause, when

excess weight gain may be a problem. In the United States and a number of other developed and developing 

countries, the prevalence of obesity is higher among women than among men. The prevalence of obesity in the

United States is highest among African-American women (48.6 percent), and is also increased in women from 

other ethnic minority groups. Furthermore, body composition differs markedly between the sexes. The typical 

percentage of body fat for 20-year-olds is 10 percent for men and 20 percent for women. By age 40, it is 20 percent for men and 30 percent for women. Thus, obesity should be considered a preeminent women’s health issue.

One aspect in which women differ from men is in the experience of fluctuating hormone levels across a

monthly cycle. These changing levels of hormones throughout the menstrual cycle in reproductive-aged women 

have been associated with altered food preferences and eating behavior which, over time, may contribute to 

nutrition-related problems, such as obesity, in certain women. The unique nutrition-related health risks women 

may experience at different points in their lives are briefly discussed below.

Childhood and adolescence. Both undernutrition and overnutrition are potential problems for young 

girls. Undernutrition can occur as a result of poverty, lack of health education, actual child neglect, or other 

factors. Overnutrition, manifesting as obesity, is a major problem for U.S. children with the prevalence of childhood obesity nearly doubling over the last few decades. This increase in obesity in children has been related to 

the availability of “junk” foods, reduced physical activity, and television watching. Nutritional risk in children 

may also be related to socioeconomic status, ethnic background, geographical location, or other factors. Finally, 

teen pregnancy is a major public health problem that puts adolescent girls and their offspring at considerable 

risk for nutritional deficiencies.
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Pregnancy and lactation. Pregnancy and lactation impose a significant physiological and nutritional 

stress on women. Undernutrition during pregnancy is associated with adverse maternal and fetal outcomes, 

while overnutrition and excess weight gain during pregnancy can lead to permanent obesity. Several studies 

have suggested that excess weight gain in pregnancy may be a contributing factor for life-long obesity in women.

Excess weight gain during pregnancy has recently been identified as a greater problem for African-American 

women than for Caucasian women, a fact which may be linked to the high prevalence of obesity in middleaged African-American women.

Mid-life and menopause. With increasing age, all individuals tend to gain fat mass and lose lean body 

mass. This unfavorable shift in body composition is related to a number of age-related chronic health problems 

in this country. Research has suggested that menopause may be associated with an increase in body fat and 

a shift in location of body fat from the periphery to the abdomen. This hormone-associated change in body 

composition has been suggested to explain, in part, the increase risk for heart disease that women experience 

after menopause.

Aging. Elderly women are at risk for a number of nutrient deficiencies which may impact their health 

status. Nutritional issues in the older population range from inadequate intakes of antioxidants, which can 

alter immune function, to low calcium intakes, which can exacerbate osteoporosis. Furthermore, nutritionrelated chronic diseases, such as diabetes and heart disease, exact a greater toll in the older population.

Current Research

We describe several of the ongoing research projects at the Pennington Center exemplary of nutritional 

issues in women’s health research which cross the spectrum from the laboratory to the clinic to the field. The 

Pennington Center’s director’s, George Bray, M.D., own research career has spanned this spectrum. Our team 

of researchers in basic, clinical, and field research have all explored aspects of issues related to women’s health 

that shed greater light on this area.

Basic research. Gender differences in the severity of obesity in humans are mirrored in animal models 

of obesity. David York, Ph.D. leads the basic obesity research program and has conducted experiments exploring

gender differences in obesity. Dietary obesity in female rodents is more profound than in male rodents when both

genders are fed a high-fat diet. Similarly, ovariectomy reduces body fat accumulation in the rat, which signals the

important role of estrogen in body fat accumulation. 

Gary Truett, Ph.D. studies the genetics of obesity in the Zucker rat. He recently observed that heterozygosity

for the fa gene may confer a survival advantage in female, but not male Zucker rats. Early in life, heterozygous

female rats are plumper than those not carrying the gene, while later in life there is no difference. This observation may help explain the persistence of obesity genes in populations.

Clinical research. It is vitally important to identify behavioral and physiologic factors that uniquely 

predispose women to overeating and thus to weight gain. In the psychosocial area, much of our clinical 

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research has focused on the following groups of women: (1) women with a history of dieting; (2) women with 

a history of binge eating; (3) women with a history of both dieting and binge eating; and (4) women who have 

not had a history of either dieting or binge eating. 

Results of studies performed by Paula Geiselman, Ph.D. show that a high-fat, high-sugar, chocolate food 

provokes overeating in all four groups of women. Furthermore, in a study of women across their menstrual cycle,

Dr. Geiselman has shown that a high-fat, high-sugar chocolate food provokes overeating in women during both the

follicular phase, when estrogen is elevated, and the luteal phase, when estrogen levels are lower and progesterone

peaks. Preferences for other types of foods, however, show differences between the follicular and luteal phases.

In the area of eating disorders, an on-going study by Monique Smeets, Ph.D. will investigate how the visual

system constructs visual images; particularly, why females who have anorexia nervosa construct visual images of

their own body as being fatter than they actually are. This study will focus on whether the visual body image is

constructed in the same manner by young women with body dysphoria and women with anorexia nervosa.

Jennifer Lovejoy, Ph.D. has conducted research on the relationship of pregnancy to later development of 

obesity. She found that women who retained 25 pounds or more of excess weight following delivery of their first

infant differed significantly in their eating behavior, with higher scores on disinhibition (overeating) and perceived

hunger. There were no differences between lean and postpartum obese women in their dietary intake, exercise,

breast-feeding habits, depression scores, or other psychological factors. 

Dr. Lovejoy has also evaluated the effects of an androgen or anti-androgen on abdominal fat and health risk 

in obese, older women. Postmenopausal women were treated for 9 months with one of the drugs or a placebo, 

and they were also instructed in weight loss by dietary means. Androgen treatment increased lean body mass 

(presumably muscle) and caused a greater loss of body fat, especially in the abdominal subcutaneous fat compartment. Visceral fat was not lost to as great an extent, resulting in a worsening of the visceral/subcutaneous 

fat ratio. The researchers concluded that increased levels of male hormones in women, which occur naturally 

at menopause, may be associated with worsening of the abdominal fat distribution; and that androgens appear 

to independently regulate visceral and subcutaneous abdominal fat.

Finally, Dr. Lovejoy has recently received a grant from the National Institutes of Health to perform a longitudinal study of the perimenopausal period. This study will focus particularly on changes in body composition,

energy balance (intake and expenditure), and insulin action in African-American and Caucasian women before 

and after the menopausal transition.

In a series of studies funded by NASA, PBRC has examined the effect of simulated weightlessness using 

28 days of complete bedrest. The purpose of these studies was (1) to improve upon the ground-based model 

of space flight by adding low doses of thyroid hormone to the bedrest protocol, and (2) to develop countermeasures that will help prevent muscle and bone loss in astronauts on extended space flights. We studied 

five women and nine men in the first round of these studies to determine whether there are differences in the

response to bedrest by gender. Initial results suggest that there may be ways in which female astronauts are 

at greater risk for problems and, in some areas, at lesser risk for problems than their male counterparts.
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James DeLany, Ph.D. is performing studies in Baton Rouge school children to determine predictors of obesity,

and to assess whether there are gender or race differences in risk factors for overweight in young children.

Field research. As part of the three-state, Lower Mississippi River Delta Human Nutrition Research 

Initiative, PBRC, along with five other institutions and the USDA-ARS, are planning a longitudinal survey of 

a cohort of area residents that will combine state-of-the-art dietary and lifestyle surveys; food supply assessment; and human biochemical, anthropometric, and physiologic measurement. The survey will provide genetic

samples for the Pennington Center database and tissue and blood archives. This resource will be a treasure for 

use in expanding our knowledge of nutrition, obesity, and other health risks, particularly in low-income, rural

African Americans.

A project directly related to primary care treatment of obesity is currently planned by Drs. Phil Brantley 

and Pam Martin. The PCOMO (Primary Care Office Management of Obesity) project will enroll 640 low-income

women across the state of Louisiana to study the efficacy of primary care obesity treatment. Pharmacological and

behavioral treatments will be studied alone and in combination for 24 months; comorbid conditions, such as 

diabetes and high blood pressure, will also be assessed.

Dr. James DeLany has a grant from the U.S. Army to study energy expenditure in female soldiers. This study

will determine the energy requirements of service women in a variety of military settings in order to provide critically important data for the determination of appropriate nutritional guidelines, including nutrient densities of

rations and appropriate energy intakes to satisfy body composition standards. The principle assessment of energy

expenditure will be made using a state-of-the-art, doubly labeled water technique. Assessments will be made in 

five key studies of women (with smaller groups of men for comparison) over a 3-year period in different military

settings. These data will provide a foundation for the adequate and appropriate nutritional guidelines of service

women and improve readiness of the services.

Why is research on nutrition and preventive medicine important with regard to women’s health?

It is now widely recognized that diet is an important factor in a number of chronic diseases that affect both

men and women. Recognition of obesity as a condition for which women may have a stronger predisposition, 

and identification of the importance of hormonal changes in the onset or worsening of obesity, can have significant public health impact. The ability to target particular times in women’s lives, such as pregnancy and

menopause, where increases in body weight may be more likely to occur, allows for the design of intervention 

programs that may reduce the health burden of obesity for U.S. women. Similarly, research on the disorders of

anorexia and bulimia may help to decrease the incidence of these serious conditions in young women. Finally,

understanding of the role of nutrition in chronic disease development in women, which may differ from its role 

in men, will help us tailor treatments and reduce morbidity and mortality from conditions such as heart disease

and diabetes. Through a combination of basic, clinical, and field research, PBRC hopes to be at the forefront 

of these types of investigations in women’s health.

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Associate Professor of Biostatistics

Tulane University School of Public Health and Tropical Medicine

Frances J. Mather, Ph.D. New Orleans, Louisiana

The Importance of Research in Identifying Factors Associated with Reduction of Preterm Births

This testimony addresses the need for further research into identification of the factors associated with 

the reduction of preterm births.

The Problem

Preterm birth. A preterm birth is a birth that occurs when the fetus is less than 37 weeks gestational age.

Preterm birth is the major pregnancy-related problem in the United States. It accounts for nearly 75 percent 

of the infant deaths in the first month of life and as much as 50 percent of long-term neurological damage in 

children.1 Nearly 60 percent of early infant deaths are found in the 1 to 2 percent of infants born at less than 

30 weeks gestational age or weighing less than 1000 grams at birth.2 It is the major contributor to low birthweight. Although rigorous estimates of costs of low-birthweight infants are not precise,16,17 annual direct 

costs attributed to preterm births in the United States have been estimated to be at least $4 billion.15,3

Who Is Affected?

Demographics. Preterm birth among black women occurs in about 12 percent of live births, approximately

twice that of white, Hispanic, and Asian women. 

Sequelae of preterm/low birthweight. Low birthweight is associated with an increased risk of subsequent

hypertension and death due to cardiovascular disease.4 Weight at birth and social conditions of childhood are

found to affect reproductive capacity.5,6 Neurological conditions found in children with very-low-birthweight 

(< 1500 grams) include cerebral palsy, and attention deficit disorders. Other conditions include retinopathy of 

prematurity, SIDS, bronchopulmonary dysplasia, and other chronic pulmonary conditions.7,8 Since 1989-91,

declines in infant mortality, largely attributed to the use of surfactant and other neonatal interventions, have 

resulted in increasing survival of these extremely preterm deliveries at risk to sequelae. 

Work to Date in the Reduction of Preterm and Low Birthweight 

Determinants of preterm and low-birthweight births. Much work is available in the determinants of 

gestational age and low birthweight, in the case of gestational duration pre-pregnant weight, prior history 

of prematurity or spontaneous abortion, in utero exposure to diethylstilbestrol and cigarette smoking; and in 

the case of low birthweight/IUGR [IUGR - IntraUterine Growth Retardation], infant sex, racial/ethnic origin 

(IUGR associated with black/Indian births), maternal height (IUGR associated with short stature), pre-pregnancy 

weight (IUGR associated with low pre-pregnancy weight), paternal weight and height, maternal birthweight, 

parity, history of prior low-birthweight infant, gestational weight gain and caloric intake (IUGR associated 

with poor weight gain), general morbidity and episodic illness, malaria, cigarette smoking, alcohol consumption, and tobacco chewing.9
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Intervention/programs. Standards of prenatal care incorporating nutritional counseling, fetal monitoring, 

testing for sexually transmitted disease, identification of genetic and other diseases, monitoring weight gain and

blood pressure, and patient education on preterm delivery have been established through the American College 

of Obstetrics and Gynecology. Social and professional support programs including nurse home visits, case management and media campaigns to encourage early prenatal care, prenatal classes, parenting classes, and male

involvement have been instituted though the National Healthy Start program and other maternal and child 

health programs. 

Failure of preterm prevention programs. A recent analysis of trends in adverse outcomes of pregnancy 

in Orleans Parish, Louisiana, over the period 1989-1995, shows increases in the proportion of women who 

initiate prenatal care in the first trimester, increases in the adequacy of prenatal care as measured by the indexes 

of Kessner and Kotelchuck, and declines in the infant death rates. These trends in improved prenatal care are, 

however, not accompanied by increased gestational duration and birthweight. In fact, there is a slight increase 

in the proportion of births with low (<2500 grams) birthweight and preterm (<37 weeks) birth. The twofold

increase in low birthweight and preterm births among black women compared to white women remains in 

spite of this increased prenatal care. Findings comparable to this are to be found in most large cities in the 

United States. 

In summary, little or no evidence is available that preterm prevention programs,10 social support for 

pregnant women, early prenatal care, education to increase awareness of the signs of preterm labor, and the 

use of tocolytic therapy to suppress uterine contractions11 have been successful.

Potential Factors Explaining Preterm Birth and Low Birthweight

Determinants of gestational duration currently under investigation include genital tract infections; antenatal

care; maternal employment; physical activity; stress and anxiety; low-birthweight caloric expenditure; antenatal

care; and vitamins and trace elements.9

Role of infections in preterm births. Promising new developments include the assessment of the role 

of infections in preterm births.12 There is some evidence that differences in colonization with bacteria associated with spontaneous delivery — Ureaplasma Urealyticum, Mycoplasma hominis, Bacteroides, and Gardnerella 

vaginalis — may explain the excess prevalence of potentially pathogenic organisms among black women when 

compared to white, Hispanic, or Asian women.13 Bacterial vaginosis is associated with the preterm delivery of 

low-birthweight infants, independently of other recognized risk factors. Treatment with metronidazole and 

erythromycin has reduced rates of premature delivery in women with bacterial vaginosis and at increased 

risk for preterm delivery.14

The Need

The burden of preterm birth falls heavily on black women, many of whom are poor. The cost of preterm 

birth is high and the sequelae longlasting and, certainly among the very low birthweight, severe and irreversible.

Recent innovations in neonatal intensive care makes it possible for greater proportions of the tiny infants to 

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survive, but not without the sequelae associated with this condition. There are about 40,000 to 50,000 of 

these very-low-birthweight infants per year in the United States who will, in succeeding years, require additional funds to address the physical, mental, and educational handicaps subsequent to preterm birth. Cuts in 

Medicaid and SSI will certainly impact the financing of needs for this growing population. A number of promising studies support the hypothesis that infections may play an important role in the incidence of preterm birth. 

I urge that research in the identification of preventive factors associated with preterm birth be made a priority. 

References

1 McCormick, M.C. The contribution of low birthweight to infant mortality and childhood morbidity. N Engl J Med 312

(1985): 82–89.

2 Goldenberg, R.L. and Andrews, W.W. Editorial: Intrauterine infection and why preterm prevention programs have failed. 

Am J Public Health 86 (1996): 781–83.

3 Update. Incidence of low birthweight. MMWR 33 (1984): 45–67.

4 Barker, D.J.P., Winter, P., Osmond, C., Margetts, B., and Simmonds, S.J. Weight in infancy and death from ischaemic 

heart disease. Lancet 2 (1989): 577–80.

5 Emanuel, I., Filakti, H., Alberman, E., and Evans, S.J. Intergenerational studies of human birthweight from the 1958 

birth cohort. I. Evidence for a multigenerational effect. Br J Obstet Gynacecol 99 (1992): 67–74.

6 Baird, D. Changing problems and priorities in obstetrics. Br J Obstet Gynaecol 92 (1985): 115–21.

7 Goldenberg, R.L. The prevention of low birthweight and its sequelae. Prev Med 23 (1994): 627–31.

8 Hack, M., Klein, N.K., and Taylor, H.G. Long-term developmental outcomes of low-birthweight infants. The Future of 

Children 5(1) (1995): 176–96.

9 Kramer, M.S. Determinants of low birthweight: methodologic assessment and meta-analysis. Bulletin of the World Health

Organization 165(5) (1987): 663–737.

10 Creasy, R.K. Preterm birth prevention: where are we? Am J Obstet Gynecol 168 (1993): 1223–30.

11 Hack, M. and Merkatz, I.R. Editorial: Preterm delivery and low birthweight — a dire legacy. N Engl J Med 333 (1995):

1772–73.

12 Hillier, S.L., Nugent, R.P., Eschenbach, D.A., et al. Association between bacterial vaginosis and preterm delivery of 

a low-birthweight infant. N Engl J Med 333 (1995): 1737–42.

13 Goldenberg, R.L., Klebanoff, M.A., Nugent, R., et. al. Bacterial colonization of the vagina during pregnancy in four 

ethnic groups. Am J Obstet Gynecol. In Press.

14 Hauth, J.C., Goldenberg, R.L., Andrews, W.W., et al. Reduced incidence of preterm delivery with metronidazole and 

erythromycin in women with bacterial vaginosis. N Engl J Med 333 (1995): 1732–36.

15 Andrews, W.W., Goldenberg, R.L., and Hauth, J.C. Preterm Labor: Emerging Role of Genital Tract Infections. Infectious

Agents and Disease 4 (1995): 196–211.

16 Long, S.H., Marquis, M.S., and Harrison, E.R. The Costs and Financing of Perinatal Care in the United States. Am J Public

Health 84(9) (1994): 1473–78.

17 McCormick, M.C. and Lee, S.K. Editorial: Estimating the Costs of Pregnancy-Related Care. Am J Public Health 84(9) 

(1994): 1376.
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Women With A Vision, Inc.

Danita M. Muse, M.S.W. New Orleans, Louisiana

African-American Women and Terminal Illnesses: Cancer, HIV/AIDS/STD, and Community Violence

It does not matter what any census will say. It does not matter how many teenage pregnancies 

we have. It does not matter about welfare reform (and we know how true those numbers are).

We die more often than any other race!

Cancer

Lung cancer. Between 1973 and 1992, the rate of lung cancer among African-American women increased

more than 100 percent, and so did the death rate. For African-American women, lung cancer is now the leading

cause of cancer deaths.

Breast cancer. Breast cancer was the second leading cause of cancer deaths among African-American women

between 1973 and 1992, with breast cancer among those between the ages of 50 and older increasing more than

38 percent. The death rate among this group has increased by 25 percent.

Cervical cancer. Between 1973 and 1992, overall cervical cancer diagnoses and deaths among American

women decreased; however, African-American women over the age of 50 remain more than twice as likely to 

develop cervical cancer and die of it than their Caucasian counterparts. For African-American women under 

age 50, the incidence of cervical cancer was higher than Caucasian women in the same age group.

We die more often than any other race!

HIV/AIDS

The Louisiana Department of Public Health and Hospitals’ Office of Public Health produced a summary 

of epidemiological data in the statewide HIV/STD Prevention Plan for 1997 recognizing the important trends

toward increased risk for African-American women. Louisiana’s rate of HIV infection in childbearing women 

is 50 percent higher than the national average and rising. New Orleans is the third poorest city in America, 

with a disproportionate percentage being African-American women.

Nationally, females represent 14 percent of the cumulative adult and adolescent AIDS cases. Of all the 

incident cases of HIV infection reported for the 20 to 24 year-old age group in 1995, 36 percent were female. 

The national trend toward a sharply increasing proportion of females in new AIDS and HIV cases is reflected in 

the epidemic in Louisiana. In Region I, females represent 105 of the cumulative adult and adolescent AIDS cases.

National-level data on new AIDS cases reported during 1995 indicated that heterosexual contact was the mode 

of exposure in 38 percent of female cases, proportionately equal to IDU exposure.

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In Louisiana, the trend toward greater female risk through heterosexual transmission is ever more marked.

Forty-four percent of new female AIDS cases reported in 1995 indicated heterosexual contact as the mode of 

exposure, compared with 25 percent attributed to injection drug use (27 percent unspecified). The rate of HIV

infection in childbearing women in Louisiana is 50 percent higher than the national average, and still increasing.

Proxy measures for HIV-risk behavior, such as case rates of syphilis and gonorrhea, indicate the potential for

increases in rates of HIV infection. Among women in Louisiana, HIV is following in their footsteps!

We die more often than any other race!

Community Violence

I have lived in the community of my fellow African Americans for a long time. They have taught me some

excellent survival skills. I have learned to be grateful for what I have, and that there is always more than one 

way to get what you need from those who have it. I have also seen a change in my community. A change where

violence has become normal and community rape occurs every time a house is not maintained. Hopelessness is 

evident in the eyes of the women I see in my communities. These women place no faith in a “system” that they

have seen take the lives of their children and their own, and they have no trust in a system that characterizes 

them as worthless.

A myth exists that suggests that we, African-American women, want to be the head of the household. 

I suggest that it is instead an issue of survival. We have families to care for and histories of doing for ourselves 

last. Everyone else comes first. We practice emergency room medicine and have little time for reading or watching the news. We feel all right, so everything is fine.

Prevention messages are never a part of our everyday existence. They are in the clinics where we go, but 

not in the neighborhood laundromats, corner stores, or beauty shops where we live. We have to go somewhere

“special” to see these messages. Why leave the community for help when the service providers we go to see do 

not care? When they say, as if we were not there, “why did she wait so long?” Why leave your community, when

none of the messages look like you? Why leave, when you have to survive? Why leave, when you have low self

esteem, and feel you are all alone?

Gaps

Hopefully, the existing gaps should be evident. Here are the top five reasons as I see them.

1. The continuing separation of women from their families. Answer: One-stop treatment. Current medical 

treatment occurs between the hours of 9:00 a.m. to 5:00 p.m. Children do not get sick at prescribed hours.

2. Why separate women’s health care by illness? One illness will have an effect on many levels of an individual’s

well being. The effects of sexually transmitted diseases, HIV, abnormal Pap smears, or cancer are not isolated 

to purely physical manifestations.
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3. Why isolate research to people who are in treatment? Individuals who are not receiving treatment should 

be questioned as to why they wait until a medical incident occurs to receive treatment. If researchers are 

afraid of the communities they serve, then they should take a look at the street outreach model, or leave 

the community alone!

4. Researchers need to be more community minded. Scouring communities only for the information that 

they seek, and then disappearing, only leaves a sour taste in the mouths of the community members.

5. After these women die from such illnesses as cancer, AIDS, and violence, what happens to their children?!! 

Do they go to bigger and better jails, overpopulated graveyards, or seldom-used colleges?

We die more often than any other race!

Organizational Description: Women With A Vision (WWAV), Incorporated

Women With A Vision (WWAV), Inc., is a minority, nonprofit community-based organization with a 

mission espousing women and their families entitlement to health services that are appropriate and responsive 

to their needs. WWAV is committed to promoting wellness and disease prevention through health education, 

early intervention strategies, and referrals among women and their families living at or below the poverty level. 

We have a history of providing HIV/AIDS/TB/STD and substance abuse resources to minority communities 

comprising individuals practicing high-risk behaviors. It is our intent to empower a neglected minority community with the tools necessary to make informed choices concerning their health. We continue to inform 

such communities of available resources before they reach critical stages of illness or before a medical crisis. 

WWAV provides a vital link between the community and service providers through one-on-one street outreach 

and community outreach.

Since the inception of our organization in 1991, we have focused our attention on a geographic area called

Central City. Central City is a crime-ridden, impoverished, and drug-inundated community. Seventy-three percent of the families living in this area have incomes 200 percent below the poverty level. The Center City area, 

with a population of approximately 65,000, is 93 percent African American. Three housing developments, the 

C.J. Peete, the B.W. Cooper, and the Guste high-low rise, are also located within its boundaries. WWAV brings

information directly to the community by recognizing and empathizing with the barriers that face many of its 

citizens (i.e., poverty, high crime, inadequate child care and transportation to traditional agencies providing 

services, the unpreparedness of traditional agencies to handle diverse clients, and a general unawareness of 

available resources or prevention approaches).

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Medical Director for Women’s Health

Louisiana Office of Public Health

Marcy Ouellette, M.D., M.P.H., T.M. New Orleans, Louisiana 

The Louisiana Office of Public Health, Division of Health Services, houses the Maternal Child Health 

and Family Planning Programs, both of which provide preventive services to women and female adolescents 

of reproductive age and their children. During fiscal year 1995-96, approximately 200,000 women (72,841 – 

family planning; 53,541 – maternity; 30,000 – STD/HIV; and 50,000 – WIC) and 148,117 children utilized our

medical and nursing services. Similar to other public health programs, these women are mainly impoverished,

underserved, and disenfransied. Despite intensive efforts, and assistance at the federal, state, and local levels,

improving the health status of the women who entrust themselves to our services remains difficult. 

Why? This is a question many of us who are committed to public health services constantly struggle with. 

Is it poverty and its enormous destructive consequences, institutionalized racism and sexism, social inequalities, 

or are there other more subtle differences among women who utilize public health services? Although research

regarding women’s health is improving, there continues to be a lag in reliable information regarding women of

color, adolescents, and the disparities that exist between women who utilize public services versus private, women

of color and whites, and among women of color themselves. Epidemiological, scientifically tested rates and prevalence among these groups is difficult to document, as are interventions that are successful. Yet, without them, 

funding to address these issues is not forthcoming.

The other side to this testimony must emphasize how, despite enormous social, economic, racial barriers, 

and fragmented health services, many women who utilize our public health services have health strengths and 

coping strategies that enable them to live healthily and productively, and raise healthy children who are safe 

and constructive. We seldom look at this. 

Why? Research historically looks at illness rather than health. To understand how women prosper and 

protect their and their children’s health and well being, despite enormous odds, would, in fact, enable us to 

design interventions based on individual and cultural strengths, which may ultimately have a greater impact. 

With the expectation that research conducted on women will involve women in the planning and design, 

implementation, evaluation, and interpretation of results of research studies, and will involve women who are 

from multiculturally and socioeconomically diverse backgrounds, we suggest research in the following areas.

• How the perception of being a public health recipient (particularly from a young age onward), where 

choice of provider and appointment days and times are usually not self selected and services are generally 

monetarily free, affects women’s self identity and self reliance, particularly one’s ability to make independent

reproductive and other healthy life choices. 

• How gender identity and responsibility are affected and contributed to by reproductive health clinics that 

primarily focus on females.
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• How well informed are women regarding informed consent as it pertains to research involving reproductive health, contraception, and STD/HIV. How comfortable are women in actually refusing to be part of a 

study? Specifically, how women who cannot say no to a study involving their reproductive health, can 

effectively say no to other issues and actions involving their reproductive health.

• Infant mortality and low birthweight disparities between blacks and whites. 

• Effects of the media on healthy gender identification and sound health practices on female adolescents 

and adult women.

• Continued multicultural, sound contraceptive research and development since 60 percent of all pregnancies

continue to be unintended.

These issues focus mainly on reproductive and sexual health care needs of women, primarily because these 

are the issues our programs address. We continue to need research addressing cardiovascular disorders, endocrine

disorders, osteoporosis, and mental health and illness, but these health concerns are not controversial and do not

come under the same political scrutiny as do reproductive and sexual health issues. To maintain and improve the

status of women, we must ensure that these issues be addressed.

. Director

The Center for Sexual Health

Tulane University Medical Center

Eileen M. Palace, Ph.D New Orleans, Louisiana

Research and scientific knowledge on the sexual health of women has lagged far behind that of men. 

Masters and Johnson (1970) estimate that at some point during a relationship, one of every two couples 

experience sexual difficulties. For women, the prevalence of orgasm disorders is estimated at 30 percent 

and the prevalence of sexual desire disorders estimated at 20 percent (DSM-III-R, 1987). This means that, 

conservatively, orgasm disorders affect over 23.5 million women and desire disorders affect over 15 million 

women in this country. The inclusion of other types of sexual dysfunction affecting women (e.g., sexual arousal 

disorders, sexual pain disorders, vaginismus) and associated psychological disorders (e.g., depression, anxiety)

would provide estimates many times greater. Despite the pervasiveness of sexual disorders in women, very little 

is known about the basic mechanisms that mediate sexual arousal and response in women; only a handful of

researchers in the country conduct research on the sexual psychophysiology of women and, as a result, research 

on women’s sexual functioning and knowledge of women’s sexual health is lacking.

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There is growing awareness of the absence of medical and clinical research on women’s sexuality and of 

the detrimental effects of our gender-biased knowledge. Research funding is needed to foster new programs of

research to (a) define the construct of sexual arousal, (b) determine valid and reliable assessment instruments, 

(c) identify an etiological model of sexual dysfunction, and (d) develop effective, empirically based treatment 

methods for the alleviation of sexual dysfunction in women. 

This testimony presents recent advances in knowledge of women’s sexual functioning and the potential 

for new research programs to revolutionize current knowledge in women’s psychological and physical health. 

It presents current findings that identify mechanisms in the etiology, treatment, and prevention of sexual healthrelated problems for women, and provides implications for new health psychology and behavioral medicine

approaches for the prevention and alleviation of psychological and medical disorders. This testimony presents 

suggestions for new research programs that, if fostered, may provide new behavioral medicine approaches to 

treatment where, instead of surgery or pharmaceutical techniques, changes in behavior and cognition are used 

to change physical problems. United research efforts are needed to instigate programs to facilitate the understanding of women’s sexual health requirements, to pursue new approaches to improve the quality of health 

care and, ultimately, to promote mental and physical sexual health for women.

Chair

Committee on Women’s Affairs

Jayashree Rao, M.D. New Orleans, Louisiana

Career Issues for Women Scientists and How to Overcome Them 

Barriers

• Women are biologically different and that has an impact on how they view science and their contribution 

to the advancement of science. 

• Socialization of women during childhood, adolescence, and young adulthood is different, and that has an

impact on the way they perceive a career in science. 

• Women’s roles, as governed by the societal norms, make it extremely difficult to participate and benefit 

from traditional programs that are now in place to foster a career in science.

• The traditional type of mentoring process does not address the gender differences in fostering the careers 

of women scientists. 

• The life cycle of women’s creativity and productivity are different and there are virtually no programs 

that address this difference. 
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Adequate numbers of women are choosing careers in science. Yet, their progress and creativity do not 

meet their full potential.

Solutions should be aimed at:

• Mentoring that is mindful of the gender differences. 

• Time course for career advancement that recognizes the women’s needs to balance multiple roles.

• Newer programs that encourage and foster senior women’s entry and progress in scientific careers.

Director, Research Area VI

United States Army Medical Research and Materiel Command

Colonel Irene M. Rich Fort Detrick, Maryland

A REPORT ON CONGRESSIONALLY DIRECTED WOMEN’S HEALTH RESEARCH BY THE DEPARTMENT OF DEFENSE

Introduction

The United States Army Medical Research and Materiel Command (USAMRMC) is pleased to participate 

in the Office of Women’s Health Research “Beyond Hunt Valley: Research on Women’s Health for the 21st 

Century.” In the last few years, targeted Congressional biomedical research funding to the Department of 

Defense (DoD) has resulted in significant advances in the spectrum of women’s health research. The DoD 

Breast Cancer Research Program (BCRP) is the largest DoD women’s health research effort. A background 

of this program will be provided with further discussion on program stewardship, program execution, 

targeted populations, partnerships, scientific management innovation, research dissemination, research 

achievements, and emerging issues. This paper will conclude with brief overviews of other DoD women’s 

health research programs.

DOD BREAST CANCER RESEARCH PROGRAM

Background

Responding to diverse groups seeking to increase breast cancer research funding, Congress has appropriated a total of $490 million for the DoD BCRP from fiscal year 1992 to 1996. An additional $112.5 million 

in FY 97 funds have been received and the Broad Agency Announcement (BAA) for these funds has been 

released. The USAMRMC was tasked to manage the BCRP. Due to the importance and visibility of the program and the fact that breast cancer research was outside its historic scientific experience, the U.S. Army 

commissioned the National Academy of Sciences’ Institute of Medicine (IOM) to provide an assessment of 

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breast cancer research and to advise the USAMRMC on scientific management strategies. The IOM recommendations were published in a 1993 report entitled Strategies for Managing the Breast Cancer Research 

Program: A Report to the U.S. Army Medical Research and Development Command. Based on this document, 

the USAMRMC has created a research funding program and management infrastructure that is innovative, 

scientifically sound, and responsive to the needs of both scientific and advocacy communities.

From an administrative perspective, it is important to note an aspect of the DoD BCRP that distinguishes 

it from other federal research efforts: DoD Congressional Special-Interest Research Program budgets are neither

requested in the President’s Budget Request nor programmed in either the Program Objectives Memorandum

(POM) or the Future Years Defense Program (FYDP). Each annual appropriation made to the DoD can only 

be considered a single budget-year appropriation with no out-year funding stream. Therefore, awards for the

research proposals funded, as well as the funding required for the scientific oversight or management throughout the period of grant performance, are provided from the single-year appropriation to fully fund both the

research proposal and the support contract to facilitate the review of annual and final progress reports and 

other grant/contract requirements, such as patent compliance.

The DoD Congressional Special-Interest Research Programs are managed by a small staff of Army and 

other DoD personnel. The program is administered with the assistance of contractors and under the recommendations of expert panels consisting of scientists, clinicians, and consumer advocates spanning the entire 

spectrum of interests related to breast cancer. To optimize its limited research resources, the DoD BCRP has 

been challenged to devise a funding strategy with high impact that is not duplicative of other research efforts. 

The program aggressively seeks to identify gaps in breast cancer research funding, enhance previous accomplishments, and contribute to a comprehensive national effort that will benefit all citizens through scientific 

innovation and technology transfer.

Program timeline. Most federally funded programs receive funding from one year to the next to accommodate a regular cycle of proposal submission and review over the course of many years. In contrast, the DoD

Congressionally directed research programs have no lifetime beyond that allotted by a single budgetary cycle 

and have tight restrictions on how and when funds may be spent. Therefore, management of the program 

requires a thorough understanding of Congressional intent and strict adherence to the timeline for obligation 

of funds. The timeline begins with the Congressional appropriation. Once funds have been officially appropriated to the DoD, there is a 2-year period for program execution. However, the timing of the release of funds of 

each appropriation has varied.

During the first program year, Congressional language is analyzed, a blue ribbon advisory panel is formed, 

an investment strategy is developed, and a solicitation for research proposals is crafted and released. During 

Year 2 of the program, proposals are received and reviewed, awards are negotiated, and funds are obligated. 

Years 3 to 6 provide for the management of funded research projects. Projects are monitored for technical 
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progress and compliance, and site visits are made to institutions based on regulatory requirements. Multidisciplinary conferences are held for scientific exchange, transfer of ideas, and dissemination of research findings.

Program execution of congressional directives for the BCRP. From FY 92 to 96, Congress appropriated

$490 million for the DoD BCRP. The program has funded research at 828 different institutions in the United 

States and abroad with a variety of funding categories to support basic and clinical research projects, training

grants, and infrastructure enhancement awards. Efficiency of operation and cost containment are hallmarks 

of the DoD effort. Administrative costs incurred in managing this nearly half-billion dollar research program 

have averaged 7.6 percent. 

Targeted populations. Despite improvements in diagnostics and treatment, access to health care resources 

and care-seeking behaviors among underserved populations remain critical concerns and objectives for the BCRP.

Consistent with the IOM recommendations, each BAA has encouraged participation by women and minorities 

and has been widely distributed to maximize exposure to scientific and medical communities. This outreach has 

been successful. For example, in FY 93/94, 70 percent (67/96) of the research proposals submitted by female 

investigators were funded, 48 percent (17/38) of the research proposals submitted by minority investigators were

funded, and 89 percent (16/18) of the research proposals submitted by female minority investigators were funded.

Further, programmatic goals include addressing the needs of minority, elderly, low-income, rural, and other 

underserved populations. 

Partnerships. Since breast cancer is a complex, multifaceted disease, the fulfillment of the BCRP goals 

requires an atmosphere of cooperation and communication across many scientific and clinical disciplines. 

The DoD BCRP supports collaboration among disciplines that traditionally may not interact with hopes of 

facilitating communication, generating innovative approaches to tackle molecular causes of breast cancer, 

and translating the knowledge gained into increased/improved detection, treatment, prevention, survival, 

and quality of life for those living with the disease. The DoD BCRP is administered as a partnership of the 

military, the scientific community, and the public. This unique partnership is one of the most important program elements. Through this distinctive interaction, the BCRP has developed a new and unique vision for 

breast cancer research and biomedical research in general. The BCRP is committed to developing continuing 

public/private partnerships between scientists and consumers that will have a lasting impact on the breast 

cancer research field.

The DoD BCRP fosters partnerships, collaborations, and interdisciplinary studies at several levels: 

(1) Universities, hospitals, laboratories, and government agencies are encouraged to work together on multiand interdisciplinary efforts. (2) Military/civilian collaborations are encouraged. (3) Diverse teams of basic 

and clinical researchers, breast cancer survivors and advocates, and cancer center administrators participate 

together in the scientific and programmatic evaluation of proposals. (4) The DoD has worked with other federal funding agencies including the National Institutes of Health (NIH), the National Cancer Institute (NCI), 

the Department of Health and Human Services (HHS), Office of Women’s Health (OWH), and the Agency for 

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Health Care Policy and Research (AHCPR) to co-fund research projects. For example, NCI and USAMRMC 

have jointly funded 12 BCRP awards in support of the National Action Plan on Breast Cancer (NAPBC).

Scientific management innovations. Among the most notable accomplishments of the DoD programs are 

the scientific management process innovations that have been developed and implemented by the USAMRMC 

and support contractors in program development, scientific and programmatic evaluation of proposals, and 

management of funded projects. Process innovations will be detailed further in the discussions of research 

stakeholders, the process of two-tiered review, consumer participation, the Idea award philosophy, criterionbased scoring in scientific review, internet access to program information, Arden logic modules, and the BCRP 

“Era of Hope” meeting.

Stakeholders. The USAMRMC is committed to providing the soundest investment of public funds for 

Congressional Special-Interest Research Programs. To accomplish this goal, the BCRP seeks to address gaps 

and urgent areas of unmet need. A standard USAMRMC strategy is to bring together key stakeholders at the 

outset of a program to harvest the collective wisdom of experts currently engaged in the battle against a particular disease. The BCRP stakeholders include key scientists, national leaders, and consumers from government,

academic, and consumer advocacy organizations. Each representative presents perspectives on the most critical

gaps in current research funding. Input from the stakeholders represents the foundation for an investment 

strategy that most effectively targets the current and critical gaps in research.

Other benefits are derived from this approach. Communication among diverse disciplines and between 

scientists and consumer advocates provides a forum from which fresh perspectives emerge transcending traditional parochial interests. This networking also catalyzes the team building needed for a shared program vision. 

In addition, the stakeholder meeting provides an opportunity for the USAMRMC to solicit nominations from 

recognized leaders for the scientific and programmatic review panels.

Two-tiered review process. Applications to the DoD BCRP are rigorously reviewed for scientific merit 

and recommended for funding based on how well the proposals fulfill defined programmatic goals. This 

approach is in keeping with the IOM recommendations for a two-tiered review process: a first tier for evaluation of scientific excellence and technical merit; a second tier to assess relevance to programmatic goals. For 

peer review, the USAMRMC established a system to accommodate novel program goals while maintaining the 

traditional rigor of federal peer-review systems. Emphasis is placed on utilization of technological resources 

to expedite administrative processes and ensure prompt referral, review, and summary statement production 

for each application. Ad hoc peer-review panels are convened to address the precise expertise of submissions. 

Panels are oriented to programmatic goals and rigorous efforts are employed to ensure standardized review 

across the many scientific panels. Diverse representation of scientific disciplines with multiple perspectives, 

expertise, and career levels is emphasized. Concerted efforts are also employed to ensure a balance of gender 

and racial/ethnic participation in scientific peer review. Consumer representatives also participate in peer 

review and are full voting members for each application.
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The second tier, known as programmatic review, is conducted by an expert advisory panel, known as the 

Integration Panel (IP). The IP is comprised of civilian scientists and clinicians from multiple disciplines and

research settings including clinical, basic, and applied health sciences, representing gender, racial/ethnic, and 

geographic diversity. The IP also includes representatives of consumer or public interests. The primary responsibility of the IP is to programmatically review proposals deemed scientifically meritorious by the peer-review 

panels and to make recommendations for award to the Commander, USAMRMC. 

In order for a proposal to be funded, it must be recommended by both levels of the system. While scientific

merit is an important criterion for award, proposals that receive high scientific merit scores in peer review, but are

judged to have low programmatic relevance, are likely to be rejected for funding. Scientifically excellent studies 

that directly address the unique focus and goals of the program are most likely to receive funding support.

The two tiers of review are fundamentally different. Unlike programmatic review, scientific peer review 

evaluates proposals as distinct submissions: they are not collectively compared. Peer review is a criterion-based

process whereby proposals are evaluated on their individual scientific and technical merit. The evaluation focuses

on issues such as the scientific innovation, rationale, feasibility, originality, and qualifications of the investigator. 

In peer review, proposals are considered in panels from a single discipline. The goal of peer review is to establish

the scientific merit of each proposal through the assignment of a scientific merit score. 

In contrast, programmatic review is a comparison-based process in which proposals from multiple disciplines compete within a common pool. At this level, proposals are compared on the basis of their scientific 

merit (as judged in peer review), programmatic relevance, and other factors such as gender, minority, and geographic distribution. The goal of the combined review processes is to develop funding recommendations that 

balance the most meritorious science across many disciplines and offer the highest promise for fulfilling 

programmatic goals.

Consumer participation. Consumer participation in decisionmaking was a key recommendation of 

the IOM. The value of consumer involvement is derived from their unique professional and personal histories.

Their first-hand experiences with the disease add a sense of passion and urgency, ensuring that the human 

dimensions of breast cancer are incorporated into program policy, investment strategy, and research focus. 

The model of consumer participation developed in the BCRP has been applied to all subsequent DoD Congressional Special-Interest Research Programs. The inclusion strategy for consumer participation in scientific 

peer review is the assignment of two consumers to each panel. Consumers are intentionally included as lay 

participants to ensure that consumer perspectives are not lost in the scientific deliberations of peer review. 

They are asked to review applications according to the relevance of the research to breast cancer patients and 

their families. Participation of consumers in peer review was implemented within the framework of a qualitative

and quantitative evaluation effort. This evaluation consisted of a pre/post-meeting questionnaire distributed to 

all participants. Preliminary findings demonstrate an increase in positive views and appreciation of consumers

among scientists and an increased appreciation among consumers of the difficulties in breast cancer research.

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Idea award philosophy. The IOM recommended the creation of a science management environment in 

which innovative and creative scientific ideas would be supported. In response, the DoD implemented the 

Idea award category. In its original configuration, the goal of the Idea category was to stimulate and reward 

speculative but especially promising and creative ideas. Ideas were specified as 2-year grants for $150 K that 

were intended to give investigators the opportunity to explore research topics that might lack sufficient pilot 

data needed to apply for a traditional award. Since FY 93, the BCRP has allocated approximately 60 percent of 

the research funds for Idea grants. The primary intent of the DoD BCRP is to promote this novel Idea generation,

which will impact the harvest of research outcomes in the future. The vision is that the work funded now will

invigorate mid-level research development by the year 2000.

Criterion-based scoring. Though peer review has been the standard approach for evaluating the scientific

merit of research proposals, optimizing the peer-review process to ensure fairness and consistency has been a 

primary DoD concern. Unique USAMRMC award categories, such as the Idea award which does not require 

preliminary data, break from existing scientific paradigms and compound peer-review challenges. The USAMRMC 

has expended great effort in confronting the multiple challenges of peer review. A key result was the introduction 

of a new scoring system in the FY 96 BCRP peer review. It was hypothesized that focusing the reviewer’s attention on specific, published evaluation criteria would result in a more consistent, uniform, and equitable review

process for all proposals. 

This hypothesis was tested in the FY 96 peer review, where panel members rated each proposal based on 

the specific evaluation criteria articulated in the BCRP BAA. Two types of ratings were used: Each of the evaluation criteria was rated on a scale of 1 (low merit) to 10 (high merit). The overall proposal was also given a 

global score using the standard NIH scoring system — scale of 1 (high merit) to 5 (low merit). Using this 

scoring methodology, criteria scores were not averaged or manipulated to determine the global score. Instead,

reviewers were asked to use the criteria scores as a guide in determining a global score. The new scoring system 

is currently under evaluation by USAMRMC. Further, there are reports that other federal funding agencies are 

now moving toward a criterion-based scoring system.

Research dissemination. A primary goal of the DoD BCRP has been to provide timely dissemination 

of program information and research findings. Internet web sites, the Arden Knowledge Management System

(AKMS), and an upcoming multidisciplinary meeting are the primary DoD research dissemination modalities.

The Congressional Special-Interest Research Programs web site (http://mrmc-rad6.army.mil) was created 

to disseminate information about the DoD research programs. A searchable database of funded research information is provided along with abstracts of funded proposals. Links are also provided to related sites, and a 

calendar of events of interest to the research community is maintained. In addition, the web site contains 

biographical information on the USAMRMC Program Management Team (PMT) along with an e-mail 

directory to allow researchers to communicate directly with members of the PMT.
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The AKMS is another database resource currently under development by the USAMRMC. This database 

is a multicomponent software tool designed to aid in the acquisition, transformation, and delivery of biomedical

knowledge. The core technology of this knowledge management system is a modular knowledge system developed by an international consortium of medical schools and health care facilities for the purpose of creating a 

powerful method of sharing decisionmaking knowledge. A major advantage of the AKMS is that it permits users 

to encapsulate their research findings into modular units of a medical knowledge base. An important feature of

these knowledge modules is that they contain language text for reading and easy comprehension, and computer

code for decision support and computer interaction. Authoring tools under development will facilitate module 

creation. Additionally, a database structure to permit assembly and storage of multiple knowledge modules for 

use by various reasoning and decision-support applications is being developed. 

The BCRP firmly embraces the concept of cooperation and communication across the many scientific and 

clinical disciplines funded by the BCRP. The intent of the “Era of Hope” meeting, scheduled for 31 October 

through 3 November 1997, is to provide the opportunity for interplay of ideas and to present the work being

accomplished in the DoD BCRP. The meeting will have three unifying themes: (1) prevention and detection, 

(2) genetics and biology, and (3) treatment and quality of life. Funded investigators from the FY 93/94 BCRP 

will report advancements made since the initiation of the program and will share the progress with fellow 

scientists. Accordingly, FY 92-95 award recipients have also been invited to attend and present their findings,

although it is recognized that the most recent awardees will have had less than a year to conduct their research 

and findings may not be yet available.

FY 93/94 BCRP research achievements. The accomplishments data provided in this document reflect

progress made during the first 2 funding years of the FY 93/94 BCRP only. Data are not yet available from 

subsequent funding years. Although the FY 93/94 program is still in its infancy, many of these grants have 

yielded research products and publications. To date, these projects have resulted in the publication of 380 

manuscripts. Seventy-nine additional manuscripts have been submitted to journals and are currently in press. 

BCRP-funded research from this period has also been presented at over 300 national and international meetings, and investigators currently hold nine patents or licensures for advances made as a result of funding 

from this program. 

Research accomplishments resulting from BCRP-funded projects are also numerous. (Accomplishments 

from other DoD programs are not yet available.) These BCRP accomplishments are reported within the general

areas of prevention, detection, treatment, quality of life, general biology, genetics, epidemiology, infrastructure, 

and training/recruitment. Many research products are multi- or interdisciplinary and, consequently, can be 

classified in more than one discipline or research focus area. The following discussion represents only a highlighting of innumerable breast cancer research achievements from this early year of DoD funding.

Prevention. Several BCRP infrastructure projects are acquiring breast cancer survival data and morbidity and

mortality information, and are identifying women at high risk for the disease. For example, BCRP investigators

found that the ratio of omega-3 to omega-6 polyunsaturated fatty acid showed a protective effect against breast 

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cancer, especially in Mediterranean populations. Estrogen analogs such as soybean estrogens were identified 

as compounds that can inhibit the proliferation-inducing effects of estrogens when given in combination with

them. Other investigators have shown that immunization with neu-DNA is effective in reducing tumors in mice.

Also, in another study, polymeric DNA showed potential to be used as an immunizing agent against tumors.

Detection. With the funding of the BCRP, several single- and multi-center clinical trials have been initiated 

to aid in the diagnosis/detection of breast cancer. In FY 95, a special initiative was launched to promote research 

in observational and interpretational errors in breast diagnostic imaging. A major goal for this program was to 

foster the transfer of optical correlator technology to diagnostic imaging. Representative achievements include 

the following examples. A reconstruction algorithm has been developed to improve the image quality of whole

body studies. The optimization of intensity and texture features has increased the sensitivity of detection algorithms and decreased the incidence of false positive images. Mammographic work stations have been installed, 

and it has been demonstrated that mammograms can be compressed and digitized simultaneously. Online data

compression was found to be potentially useful for telemammography and other digital applications, improving

overall digitization and compression performance. BCRP investigators have demonstrated that capillary x-ray 

optics are suitable for enhancing contrast and performing beam shaping to match with digital detectors. Capillary optical devices can also significantly improve contrast and resolution of digitized phosphor plate imaging 

systems. Using ultrasonic tomography, investigators have shown that tissue type can be reliably differentiated 

by this technique.

Advances have also been made in the detection of cellular abnormalities in breast cancer. Investigators have

identified deletions and rearrangements in specific chromosome regions in breast cancer. An assay has been developed to detect BRCA1 germ line mutations. Investigators also discovered that loss of imprinting (LOI) in tumor

stromal cells may lead to novel clinical strategies for better management and treatment of breast cancer. 

Treatment. Funded BCRP investigators have made progress in several different areas of breast cancer treatment. Nearly 400 patients have been entered into the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) 

trial for therapy, treatment, and aftercare. Investigators demonstrated that deferoxamine appears to interact 

successfully with doxorubicin to inhibit the growth of some breast cancer cell lines. The efficacy of doxorubicin

was improved by delivery of the drug in anti-Her2 immunoliposomes, which also reduced systemic toxicity. 

Several drugs that affect micronucleation and could be useful for the treatment of breast neoplasms have also 

been identified. Investigators have demonstrated the potential of polynucleotide immunization for tumors. 

In addition, CEA- and HER-2/neu-expressing polio virus-based vaccines have been developed. Proliferative 

effects of estrogen have been successfully blocked with ICI164384 and antibody. Antigen mimicry to HER-2/

neu has been determined, and the anti-idiotype monoclonal antibodies (Ab2) generated have been evaluated. 

An adenovirus vector that is selectively lethal to breast cancer cells has been generated, and strategies for 

tumor-specific gene delivery are being developed. Researchers performed a study that showed that psychotherapy conducted via the telephone is an effective approach for reaching patients who have difficulty 

accessing care, but is not an effective approach for influencing disease outcome. 
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Quality of Life. The BCRP has maintained the goal of improving the quality of life of breast cancer patients.

Some examples of BCRP-funded projects include pain management, benefits of counseling, access to care, and 

care following treatment. In one study, investigators completed survey data collection on a needs assessment 

from health professionals providing pain management for minority women with metastatic breast cancer. Another

study showed that most respondents preferred using an automated message system to accessing a live counselor. 

In addition, claims data reflected a low use of radiographic surveillance testing but high use of physician office 

visits in the 36 months after initial treatment for early-stage breast cancer in the population studied. 

Results also indicate the need to further address specific concerns/issues of ethnic groups. For example, 

culturally sensitive trends have been identified among elderly Puerto Rican women regarding the belief that 

it is inappropriate to examine one’s own breasts or to have clinical breast examinations. Researchers have also

shown that increasingly larger numbers of women with breast cancer resort to one or more unconventional 

therapies and that there are ethnicity/race-dependent differences in the unconventional therapies chosen. 

General Biology. Investigators funded by the BCRP have developed model systems that can be used 

to characterize mechanisms involved in the pathology of breast cancer, tumor progression, and metastasis. 

New cell lines expressing molecules relevant to breast cancer (e.g., MHCII, B7, etc.) have been generated, 

and model systems for studying apoptosis in MCF-7 breast carcinoma cells have been developed. Additionally, 

animal models have been developed and used to study parathyroid-related protein and androgen biosynthesis.

Investigators have also developed a variety of biological assays for the measurement of essential molecules or 

their complexes. BCRP investigators have elucidated cell cycle kinases, such as cyclin D1 and cyclin E1, and 

have demonstrated that cyclin D1 is overexpressed specifically in breast cancer cells. In addition, novel substrates for protein kinase C (PKC) and epidermal growth factor receptor (EGFR) have been identified.

In the area of tumor progression, funded investigators have identified an angiogenesis factor that increases 

with tumor growth; found that epithelial vascularity increases with tumor progression; shown a positive correlation between tumor microvessel density and tumor size; identified five peptide inhibitors of the estrogen 

receptor; demonstrated that factors like Matrilysin (MAT) and transforming growth factor (TGF)-alpha accelerate

mammary tumor formation, whereas factors such as corticosteroid-binding globulin (CBG) and sex hormonebinding globulin (SHBG) Type II are negative regulators of breast cancer cell growth; identified several variants 

of the estrogen receptor in both normal and breast cancer cells; shown a correlation between the overexpression 

of certain variants of estrogen receptor and poor prognosis; and identified a tyrosine protein kinase in the focal

adhesion complex that is essential for tumor growth and invasion. 

Additionally, BCRP-funded projects have advanced biomedical knowledge of metastatic processes. 

Investigators have identified novel monoclonal antibodies that act against degradative enzymes (e.g., EMMPRIN,

Seprase, and DPPIV) involved in metastasis and invasion. Biological factors have been produced and are being 

tested as inhibitors of proteases involved in metastasis. Researchers identified new markers (e.g., Trf, Cytostatin I,

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and lysyl oxidase levels) that are present in breast cancer and may show a correlation with metastasis. 

Laminin-5 and alpha-6 integrin were characterized as potential indicators of invasive potential and were 

shown to be essential in sustaining the growth and survival of highly metastatic breast cancer. 

Genetics. The BCRP investment in genetics research has yielded a significant gain that will benefit both 

the research community and the general public. Funded investigators have identified and/or characterized novel 

oncogenes and proto-oncogenes (e.g., alternative Her-2/neu proto-oncogene, int-3 oncogene, and Notch-4 protooncogene); tumor suppressor genes (e.g., a new breast cancer tumor suppressor gene on chromosome 17, which 

is not p53); promoters, regulatory elements, and DNA-binding proteins (e.g., FAP-1, crf, and Brn-2); and genes

involved in cell cycle regulation and tumor development (e.g., Nova-1, CD44, Muc-1, and DCC). In addition, 

the roles of different oncogenes (e.g., H-ras and K-ras) in chemical carcinogenesis are being elucidated. Investigators have made great strides in the characterization of the tumor suppressor gene p53 and its mutants, demonstrating that it is the transcription transactivation function of p53 that is essential for tumor suppressor activity. 

Epidemiology. Funded BCRP investigators have added significantly to the epidemiological understanding 

of breast cancer risk factors. BCRP researchers have shown that increased breast cancer risk is associated with 

high sunlight exposure, high residential solar radiation, and high dietary Vitamin D intake. One study provided 

a comprehensive and descriptive statistical analysis of risk factors and genetics of breast cancer in a large sample 

of African-American women. Data collected in another study indicate that racial/ethnic and socioeconomic 

disparities in breast cancer survival are unlikely to be explained by differential distributions of prognostic 

biomarkers. In the area of breast cancer prevention, investigators demonstrated that monounsaturates have 

a very strong protective effect against breast cancer in Mediterranean populations. 

Infrastructure Enhancement. BCRP accomplishments in the area of infrastructure enhancement have had 

far-reaching effects. Eleven new mutant strains have been developed, as have new, cost-effective techniques for

mouse embryo cryopreservation. Ten new breast-related cell lines have been developed. New repositories have 

been established — over 8,000 samples have been collected and over 5,000 tissue products have been provided 

to investigators. Twelve investigators have used the University of California, Los Angeles/University of Southern

California (UCLA/USC) Tissue Bank to perform 12 studies, and more than 50 investigators have utilized the 

Breast Cancer Cell Line Resource Core Facility resulting in at least 48 publications. 

Training Programs. An important goal and success of the DoD BCRP has been the infusion of new investigators into breast cancer research. Predoctoral training programs have been established at 17 institutions — 

30 trainees have been recruited into these programs, and three have graduated with doctoral degrees. Individual 

fellowships were awarded to 72 predoctoral trainees and 83 postdoctoral trainees. In addition, 41 career development awards were made, and five established investigators have taken sabbaticals in breast cancer research 

that were funded by the BCRP.
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EMERGING BREAST CANCER RESEARCH ISSUES

While the DoD BCRP has made tremendous strides in addressing the complexity of breast cancer research

requirements and developing contemporary and responsive science management strategies, there is an acute 

realization that tremendous gaps remain and many questions are yet to be answered. The following is but a very

brief highlight of the myriad emerging requirements, but these patient and system issues must be addressed if 

the current momentum in breast cancer research is to be maintained and optimized.

Patient Issues

Heightened concern remains for the patient afflicted with breast cancer. Increased sensitivity to the spectrum of issues surrounding patient care including psychosocial-sexual, quality of life, and cultural dimensions 

is needed on all fronts. Answers to questions of hormonal deprivation/replacement and childbearing for the 

patient with breast cancer remain elusive. Improving access and utilization of health care services, especially 

to underserved populations, remains a major challenge. The explosion of diagnostic and treatment complexities

demands improved education and information services enabling each patient to have optimal resources for decisionmaking. Consideration of the ethical dilemmas posed with each new diagnostic and treatment advancement

must become standard practice. Finally, prevention of breast cancer is perhaps the most important and complex

arena yet to be addressed. Preventing breast cancer includes addressing the multiplicity of amorphous factors

including genetics, environment, and lifestyle. 

System Issues

System issues with breast cancer research are formidable. Initial gene research and vaccine development 

efforts are offering immense promise but still remain in their early infancy. New detection and treatment modalities addressing the total human system, not only regional dimensions, are required. An urgently needed 

requirement is an intense focus on translational research affording an opportunity to merge interdisciplinary 

expertise and insights for all model systems including invertebrate, non-mammalian, and human systems in

addressing the myriad breast cancer questions. These requirements are complex and enormous. Perhaps most

important are (1) the recognized requirement for enhanced coordination among all agencies and researchers, 

and (2) the creation of additional national infrastructures supporting technologies and rare specimens. 

OTHER DOD WOMEN’S HEALTH RESEARCH PROGRAMS

While the DoD BCRP is certainly the largest and most recognized Congressionally mandated research 

program, other targeted efforts are also making significant contributions in the women’s health research arena.

Defense Women’s Health Research Program

With a combined total strength of 340,000, women represent nearly 14 percent of the total active duty 

force of the U.S. military and 16 percent of reservists. Despite the increasing role of women in the military, 

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there is a dearth of research into the demands and specific health risks facing military women. Congress 

responded to these issues by appropriating $40 million in FY 94 for the DoD Defense Women’s Health 

Research Program (DWHRP). This program was continued in FY 95 with an additional $40 million. The goal 

of the DWHRP was to combat health problems that are unique to military women, are especially prevalent 

among military women, or have a large impact on mission performance. The DWHRP emphasized four broad

research areas: operational effectiveness, health promotion and disease prevention, psychological health issues 

related to female integration into a hierarchical male environment, and access to and delivery of gender-specific

health care.

Collectively, the DWHRP has awarded 142 grants for intramural and extramural research projects across 

a spectrum of basic, clinical, and applied research areas. Many unique dimensions of military health issues 

were addressed with funding in occupational and material hazards, performance issues, protective clothing 

and equipment, and psychosocial aspects of military life. In addition to the research projects, the DWHRP 

made a substantial investment in infrastructure enhancement. In FY 95, Congress directed the DoD to develop 

a database to facilitate long-term research issues related to the health of military women and to develop an 

information clearinghouse to serve as a resource for clinical, research, and policy issues affecting military 

women. In response, the DWHRP allocated $2.6 million and $1.2 million for the Defense Medical Epidemiologic Database (DMED) and the Defense Women’s Health Information Clearinghouse (DWHIC), respectively.

The DMED was developed to facilitate long-term research on issues related to the health of military 

women. As a comprehensive Triservice effort, the DMED provides access to longitudinal personnel and hospitalization data, enabling cohort or case-control studies and analysis. Epidemiologic studies can be completed 

on the DMED in less time than was previously required. The DMED structure accommodates a public access 

web site and both remote and direct access user capabilities. This database was designed to incorporate additional data (death, disabilities, deployments, etc.) as they become available in a semantically equivalent format

across the three services. The system is currently in the final phases of development and is expected to be 

available for use in September 1997.

The DWHIC was directed by Congress to ensure that military women, those who provide their health 

care, and those charged with ensuring their safety and effectiveness all have the required medical knowledge. 

The DWHIC is available on the internet at http://www.4woman.org. Key resources in the DWHIC include 

health information beneficial to all women, special features addressing the needs of military women, listings 

of past and present research studies on Defense women’s health, forums to ask questions or provide input, 

special reports on selected military topics, listings of military health care facilities around the world, an upto-date directory of researchers active in military women’s health, and links to the National Women’s Health 

Information Center. As part of the DWHIC, a toll-free referral phone line (1-800-994-9662) is available to 

provide access to skilled health information specialists who can provide tailored referrals to valuable sources 

of women’s health information.
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Osteoporosis Research Program

Congress appropriated $5 million in FY 95 for a DoD Osteoporosis Research Program. Following the 

model used to implement the BCRP, an IP was constituted to provide input for the program focus. A BAA 

was released, and 108 proposals were received in response. Ultimately, five grants were awarded that addressed

genetic analyses of peak bone density; optimization of fibroblast growth factor (FGF)-1 as an anabolic agent for

osteoporosis; assessments of bone turnover, menopause, aging, and ethnicity as risk factors; mechanisms of 

thyroid hormone-induced osteoporosis; and oral bone loss as a risk factor for osteoporosis.

Ovarian Cancer Research Program

For FY 97, Congress appropriated $7.5 million for a DoD Ovarian Cancer Research Program (OCRP). 

The Congressional language directs the DoD to implement a comprehensive preventive program in ovarian 

cancer that includes prevention planning, implementation, and development planning. The language also 

specifies that eligible institutions are limited to NCI-designated Comprehensive Cancer Centers. The OCRP 

is currently in the planning stages, with a scheduled release of the BAA in July 1997.

CONCLUSIONS

The DoD is a relatively new player in the women’s health research arena. The traditions of focused military determination and operational capabilities and the infusion of creative science management to expediently 

and responsibly fund the most urgently required research have enabled the DoD to become a catalyst for new

insights, technologies, and partnerships across the spectrum of women’s health research issues.

Co-Coordinator

Medical Professionals/Persons with CFIDS/CFS

Co-Founder

The North Coast San Diego CFIDS Support Group

Meghan-Morgan Shannon, M.S. Cardiff, California

Thank you for inviting me to share this vital information that I have collected concerning medical 

professionals who are getting sick with this nebulous and mysterious disease. The U.S. Centers for Disease 

Control and Prevention (CDC) has called it chronic fatigue syndrome. However, as I testified before the Office 

of Research on Women’s Health at the National Institutes of Health in Washington, D.C. on June 6, 1991, I call 

it acquired immune dysfunction syndrome, non-HIV. Not all medical professionals with CFIDS (MPWCs) feel 

comfortable with this label.

The facts indicate that health care workers are getting sick and we are being left without health care. 

We live under the poverty level. We are a drain on the society.

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Cluster outbreaks of CFS/CFIDS/ME, etc., have been documented since 1934 and possibly earlier. 

The National CEBV (Chronic Epstein Barr Viral) Syndrome Association in Portland, Oregon, did an in-depth 

survey with Minnan, Inc., Glenview, Illinois on February 25, 1986. The results showed that health care 

workers were the highest risk, teachers were the second highest. 

Dr. Bell, a well-respected medical doctor from Harvard University who works with children with CFS/CFIDS/ME,

has been quoted as saying “health care workers are at the highest risk and, indeed, are getting sick.” In 1992, at 

the Albany, New York Conference for Chronic Fatigue Syndrome, Dr. Leonard Jason, et al., presented compelling

evidence that health care workers were at the highest risk.

It is no accident that most support group leaders in the United States are from the health care field. When 

I say health care field, I include R.N.s, medical technologists, secretaries, respiratory therapists, M.D.s, etc. 

As a result of my statement in 1991, Gail Dahlen, R.N., former OB/GYN lead nurse and instructor of the 

Long Beach OB Hospital, joined me in starting a support group for MPWCs in 1992. Since 1994, we have advertised in the North Carolina CFIDS Support Group Journal five or six times. We now have nearly 600 MPWCs in 

our data and possibly hundreds more that have not responded back to us from the first contact. This journal 

reaches 20,000 people. Recently, through the efforts of the editor of our newsletter (Lori Clovis), we are now 

online and are receiving two to three letters a day, from health care workers who are ill.

We have observed several patterns that may be of interest to the scientific community. The Hepatitis B 

vaccine seems to have triggered at least ten of the people in our first group of 150. When others are asked 

directly if they received the HEP B vaccine, we find that there’s a possibility of more persons whose CFS/

CFIDS/ME started with that vaccine. Most infected individuals have worked in emergency care, or intensive 

care units, such as Gail and I, and became ill when a “flu” was in the community and we had treated those 

people. You may see our stories in the book that says “MPWCs Stories.” I have the booklet with me. It appears 

that the doctors at highest risk are OB/GYNs and family practitioners.

I know exactly when and where I got sick. It is well documented in my medical records as well as in 

JAMA, 1983. I was working at Children’s Hospital in San Diego in 1980 when an outbreak of an adenovirus 

went through the hospital and killed several children. It infected about 10 to 15 percent of the staff over the 

next 3 years and continues even to this day. Since then, I have learned that the leading neonatalogist, Dr. Morton

Cohen, who tested culture-positive as well as having high titers for the adenovirus, committed suicide in the 

late 1980s. He was diagnosed as “depressed.” 

An R.N. named Sally worked at the hospital during the viral incident in the 1980s. She continued to work

there through 1993. I have recently learned that she has also committed suicide. She was diagnosed as being

addicted to Vicodin, which she was taking for severe pain and lack of energy. She was “rehabilitated” from her 

drug addiction in 1992. Her physical illness was never addressed. Her pain was unbearable and she killed herself.
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As my friend Gail Dahlen expresses so often, “How can the very institutions to which we dedicated our 

lives turn their backs on us and allow us to either commit suicide or live on the meager social security benefits 

that put us well below the poverty line?” 

Having spoken with Dr. Elaine DeFrietis, formerly of the Wistar Institute in Pennsylvania, and Dr. Garth

Nicholson, of the MD Anderson Cancer Center, Houston, Texas, I agree with them that this is a multiple insult 

to the immunological and neurological systems of the body. Of course the health care workers are at the highest

risk, not only to the viruses and the bacterias and the mycoplasmas, but also to environmental toxins that are 

common in a hospital environment. 

I wonder, at times, if CFS/CFIDS/ME (myalgic encephalomyelitis) kicks in autoimmune responses such 

as lupus, multiple sclerosis, diabetes, rheumatoid arthritis, etc. Could it be that if someone studied the health 

care workers we might find some common threads tying all this together? 

I am appalled that the United States is using the MMPI (a test for personality disorders) to diagnose this 

disorder. However, I do believe that once diagnosed with a physical illness such as CFS/CFIDS/ME, the MMPI 

can be useful in helping to treat the patient.

If health care workers are ill, how can we have a health care plan in America? Who will take care of the 

sick? Being ill, or disabled, is truly a political issue. As a woman who is a feminist, I now truly understand 

the statement that the “personal is political.”

President, DES Action USA

Amanda Sherman Oakland, California

Organizational Summary for DES Action USA

DES Action USA is a national nonprofit organization representing an estimated 10 million mothers, 

daughters, and sons exposed to the drug DES (diethylstilbestrol).

The purpose of DES Action USA is to provide education and support to those persons exposed to DES, to

increase public awareness about DES so that individuals can discover if they are exposed, and to educate medical

professionals so they can provide knowledgeable services to DES-exposed people. We also seek to keep public

attention on the story of DES as a reminder of the need for vigilance in regard to health care practices.

DES Action USA and the DES Cancer Network are the only consumer groups to which DES-exposed 

Americans can turn for support, information, and education on the following subjects. 

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• Facts about DES, a synthetic estrogen, and numbers exposed in the United States.

• Health effects for DES daughters resulting from in utero exposure to DES.

• Previous research efforts led by the Office of Research on Women’s Health, National Institutes of Health.

• Present and pressing research questions faced by DES daughters.

Institute of Women and Ethnic Studies

Denise O. Shervington, M.D., M.P.H. New Orleans, Louisiana

Women of Color Reproductive Health Forum

The Institute of Women and Ethnic Studies (IWES) is a nonprofit 501 (C)(3) organization dedicated to

improving the physical, mental, and spiritual health and quality of life for women, adolescents, and people 

of color, in particular the poor. The overall goal is to develop culturally proficient, multidisciplinary and holistic

health intervention programs, activities, and research models. The Institute of Women and Ethnic Studies is 

recommending a new approach, a restructuring of biomedical research that would include the full representation 

of ethnic groups in the strategic planning, discovery, development, testing and evaluation, and distribution of 

new reproductive health drugs and devices.

• The development of safe and effective contraceptives must be encouraged and supported:

– Contraception must not be used as a vehicle for coercive social policy.

– Contraception must not be separated from disease protection (STD/HIV) but instead should be 

integrated into a holistic approach to women’s health.

– Contraception research agenda should be expanded to include more contraceptive options for men.

• New FDA regulations for the study and evaluation of gender and racial differences in the clinical evaluation 

of drugs must be encouraged and supported:

– Increase the participation of subgroups (by gender, race, age) in clinical trials, especially when 

medically important.

– Increase the analysis of the pharmacodynamics and pharmacokinetics among subgroups.

– Encourage clinicians of color to participate in clinical trials.
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• FDA must monitor post-marketing surveillance of drug safety and efficacy.

• A system must be developed for reporting, monitoring, and responding to consumer and/or providers’ 

reports of side effects.

• A system must be established for safeguarding against drug misuse (by misleading marketing to consumers 

or inappropriate prescribing by providers).

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Sheraton New Orleans Hotel

New Orleans, Louisiana

June 11-13, 1997

AGENDA

WEDNESDAY, JUNE 11, 1997

PREMEETING ACTIVITIES: PUBLIC HEARING

11:00 a.m. Working Meeting/Lunch

Task Force

Advisory Committee

Local Hosts

Planning Committee

Rapporteurs

1:00-5:00 p.m. Public Testimony: The Women’s Health Research Agenda for the 21st Century

Welcome and Introductory Remarks 

Dr. Vivian W. Pinn

Dr. Ann Anderson

I. State of Knowledge in Women’s Health Across the Life Span

II. Sex and Gender Differences — Impact on Women’s Health

III. New Priorities for Research on Women’s Health

IV. Environmental, Genetic, Hormonal, Nonhormonal, and Other Factors 

that Impact on Women’s Health

V. Career Issues for Women Scientists and How To Overcome Barriers

5:15-6:00 p.m. Meetings/Interviews with Testifiers, Participants, and Local Press

6:00-7:30 p.m. Meeting with Task Force/Ad Hoc

Working Group and Cochairs

Local Hosts

Working Dinner

Dr. Vivian W. Pinn

BEYOND HUNT VALLEY: 

RESEARCH ON WOMEN’S HEALTH

FOR THE 21 S T CENTURY
124

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THURSDAY, JUNE 12, 1997

SCIENTIFIC WORKSHOP DAY 1

Physiological, Psychosocial, and Pharmacologic Differences Between Women and Men

8:30 a.m. Opening Plenary Session 

Dr. Vivian W. Pinn

Welcoming Remarks and Introductions 

Dr. Judith H. LaRosa

Dr. John Estrada

Ms. Sybil Morial

Comments 

Dr. John LaRosa

Chancellor, TUMC

9:00 a.m. Overview: Beyond Hunt Valley: Research on Women’s Health for the 21st Century

Dr. Vivian W. Pinn

9:30 a.m. Plenary Address — Is It All Steroidal Sex Hormones?

Dr. Michael Lockshin

Moderator

Dr. John Estrada

10:00 a.m. Break

10:30 a.m. Panel Discussion: Physiological, Psychosocial, and Pharmacologic Differences 

Between Women and Men

Moderator

Dr. Shiriki Kumanyika

Physiological Differences Between Women and Men 

Dr. Marianne Legato

Psychosocial Differences Between Women and Men 

Dr. Vickie Mays

Pharmacologic Differences Between Women and Men 

Dr. Raymond Woosley

Biological homogeneity exists. Similarly, differences exist, especially between the sexes. 

For too long these differences were not appreciated — from the most basic cellular level 

to the vast expanse of behavior. What’s the same and what’s different? How do the 

differences affect research design and execution, health status, and health care?

12:00 p.m. Charge to the Working Groups

Dr. Marianne Legato

Dr. Donna Dean

12:30 p.m. Lunch
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1:30 p.m. Breakout to Working Groups 

Prenatal, Infancy, and Childhood Years (prenatal to puberty)

Adolescent Years (puberty to 18 years)

Reproductive and Middle Years

Perimenopausal and Postmenopausal Years

Elderly and Frail Elderly Years (65+)

3:30 p.m. Break

4:15 p.m. Working Group Interim Reports

Dr. Marianne Legato

Dr. Donna Dean

5:30 p.m. Adjourn

6:00 p.m. Reception

New Orleans Jazz Reception — Tulane/Xavier Center for Bioenvironmental Research

FRIDAY, JUNE 13, 1997

SCIENTIFIC WORKSHOP DAY 2

9:00 a.m. Comments

Dr. Vivian W. Pinn

9:15 a.m. Plenary Address: Emerging Issues in Research: Environment, Genetic and Genomic, 

and Hormones

Dr. John McLachlan

Moderator

Dr. Terry Damstra

10:30 a.m. Break

10:45 a.m. Concurrent Working Groups continue

12:00 noon Break

12:15 p.m. Lunch

Introduction

Dr. Judith LaRosa

Speaker

The Honorable Lindy Boggs

1:30 p.m. Working Group Reports

Dr. Marianne Legato

Dr. Donna Dean

3:00 p.m. Closing Remarks/Adjourn

Dr. Vivian W. Pinn
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Gerald S. Berenson, M.D.

Director, Center for Cardiovascular Health

School of Public Health

Tulane University Medical Center

New Orleans, Louisiana 

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 

Mary L. Bowers

Program Liaison Specialist

Office of Women’s Health

Dallas, Texas

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

Professor and Director

Center for Health Policy Research

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 

Diane Brown, Ph.D.

Professor and Director, Urban Health Program

Wayne State University

Detroit, Michigan 

Michael Brown

Health Scientist, Office of Women’s Health

Centers for Disease Control and Prevention 

Atlanta, Georgia 

Molly Chatterjee, M.D.

Professor, Director of Maternal Fetal Medicine

Department of Obstetrics and Gynecology

Meharry Medical College

Brentwood, Tennessee 

Margaret M.L. Chu, Ph.D.

Environmental Scientist

National Center for Environmental Assessment

Office of Research Development

U.S. Environmental Protection Agency

Washington, District of Columbia

Beyond Hunt Valley: 

Research on Women’s Health for the 21st Century

NEW ORLEANS, LOUISIANA

JUNE 11-13, 1997

PARTICIPANTS

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

Dean and Professor

Nell Hodgson Woodruff School of Nursing

Emory University

Atlanta, Georgia 

Geriane Alexander, Ph.D.

Assistant Professor, Department of Psychology

University of New Orleans

New Orleans, Louisiana 

Ruth A. Anderson, D.D.S.

Associate Professor, Pediatric Dentistry

College of Dentistry

Howard University

Washington, District of Columbia

Valerie J. Andrews, M.J.

Editor, Spectrum Unlimited

Journal for Minority Medical Students

New Orleans, Louisiana

Marietta Anthony, Ph.D.

Deputy, Office of Research on Women’s Health

Food and Drug Administration

Rockville, Maryland

Marilyn N. Arnold

Vice President, Clinix International, Inc.

Chicago, Illinois

Claudia R. Baquet, M.D., M.P.H.

Associate Dean

University of Maryland School of Medicine

Baltimore, Maryland

Evelyn Bartfield, Ph.D.

Assistant Professor, School of Dentistry

Marquette University

Milwaukee, Wisconsin

Consuelo Beck-Sagúe, M.D.

Associate Director, Minority and Women’s Health

Centers for Disease Control and Prevention

Atlanta, Georgia
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VOLUME 5

Mary T. Chunko, M.A.

Information Development Specialist

Office of Research on Women’s Health

National Institutes of Health

Bethesda, Maryland 

Lisa Cox

Program Director

National Women’s Health Network

Washington, District of Columbia

Terri Damstra, Ph.D.

Special Assistant to the Director

Tulane/Xavier Center for Bioenvironmental Research

Tulane University Medical School

New Orleans, Louisiana 

Katherine Davenny, M.P.H.

Research Epidemiologist

Clinical Medicine Branch

Division of Clinical Services Research

National Institute on Drug Abuse

National Institutes of Health

Rockville, Maryland 

Barbara J. Davis, M.D.

Environmental Carcinogenesis Program

National Institute of Environmental Health Sciences

National Institutes of Health

Research Triangle Park, North Carolina 

Anthony Del Conte, M.D.

Associate Director, Clinical Research

Wyeth-Ayerst Research

Radnor, Pennsylvania 

Linda DePugh

Administrative Assistant

Division of Health Sciences Policy

Institute of Medicine

National Academy of Sciences

Washington, District of Columbia

Bobbie Dill, R.N., B.S.N.

Program Director

Behavioral Medicine Solutions of Virginia

Roanoke, Virginia 

James E. Dill, M.D.

President-Director

Behavioral Medicine Solutions of Virginia

Roanoke, Virginia

Eloise D. Dixon, M.S.W.

Director, Counseling Center

Xavier University

New Orleans, Louisiana 

Chhanda Dutta, Ph.D.

Health Scientist Administrator

Geriatrics Program

National Institute on Aging

National Institutes of Health

Bethesda, Maryland 

Joan P. Eitzen, Ph.D.

Director, Health Promotion and Wellness

U.S. Army

Edgewood (APG), Maryland 

Carolyn Evans, M.S.W.

Clinical Program Director

Grace House of New Orleans, Inc.

New Orleans, Louisiana 

Loretta Finnegan, M.D.

Director, Women’s Health Initiative

National Institutes of Health

Federal Building

Bethesda, Maryland 

Wonda L. Fontenot, Ph.D.

Executive Director

Wannamuse Institute

Opelousas, Louisiana 

Julia B. Freeman, Ph.D.

Director, Centers Program

National Institute of Arthritis and 

Musculoskeletal and Skin Diseases

National Institutes of Health

Bethesda, Maryland 

Irma E. Goertzen

President and Chief Executive Officer

Magee-Women’s Hospital

Pittsburgh, Pennsylvania 

Julie E. Goslee, Pharm.D.

Assistant Professor of Clinical Pharmacy

College of Pharmacy

Xavier University of Louisiana 

New Orleans, Louisiana 

Phyllis Greenberger, M.S.W.

Executive Director

Society for the Advancement of Women’s 

Health Research

Washington, District of Columia

Alton E. Hadley

Assistant Secretary

Department of Health and Hospitals 

State of Louisiana Office of Alcohol and Drug Abuse 

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

B. Joe Hailey, Ph.D.

Professor, Psychology Department

University of Southern Mississippi

Hattiesburg, Mississippi 

Sandra J. Hamilton, R.N., F.N.P. 

Director

National Black Leadership Initiative on Cancer

Instructor and Assistant Clerkship Coordinator 

Department of Internal Medicine

Meharry Medical College

Nashville, Tennessee 

Eleanor Hanna, Ph.D.

Special Expert, Division of Biology and Epidemiology

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Bethesda, Maryland 

J. Taylor Harden, Ph.D., R.N.

Assistant to the Director for Special Populations

National Institute on Aging

National Institutes of Health

Bethesda, Maryland 

Suzanne G. Haynes, Ph.D.

Assistant Director of Science

Office of Women’s Health

Public Health Service

Washington, District of Columbia

Saletta Holloway

Council Representative 

29th District, Nashville and Davidson Counties 

Meharry Medical College 

Nashville, Tennessee 

Sharon D. Hunter

Contracting Officer, U.S. Coast Guard

Grand Alameda, California 

Anna M. Jackson, Ph.D.

Professor, Assistant Dean for Student Affairs

School of Dentistry, Meharry Medical College

Nashville, Tennessee 

Carol Jackson, M.P.A., R.N.

Assistant Professor and Deputy Director

Area Health Education Centers

Director, AIDS Education and Training Center

Department of Family and Preventive Medicine

Meharry Medical College

Nashville, Tennessee 

Wendy Johnson

Reporter, The Washington Blade

Washington, District of Columbia

Winniefred Jones, M.N., R.N.

Assistant Professor, Charity School of Nursing

Delgado College

New Orleans, Louisiana 

Marlene Keeling

Founding Director, CANDO

Houston, Texas 

Maurice Knuckles, Ph.D.

Assistant Professor, Director, Environmental Health

Department of Family and Preventive Medicine

Meharry Medical College

Nashville, Tennessee 

Shiriki Kumanyika, Ph.D., R.D., M.P.H.

Professor of Nutrition and Epidemiology

Head, Department of Human Nutrition and Dietetics

University of Illinois at Chicago

Chicago, Illinois 

Verna E. Lee

Program Manager

Center for Bioenvironmental Research

Tulane University

New Orleans, Louisiana 

Richard R.J. Lewine, Ph.D.

Professor and Director of Psychiatry

Schizophrenic Disorders Program

School of Medicine, Emory University

Atlanta, Georgia 

Marva L. Lewis, Ph.D.

Assistant Professor, School of Social Work

Tulane University

New Orleans, Louisiana 

Jennifer C. Lovejoy, Ph.D.

Assistant Professor

Pennington Biomedical Research Center

Baton Rouge, Louisiana 

Barbara S. Lynch, Ph.D.

Director, Technical and Logistical Support Services

Prospect Associates

Rockville, Maryland 
129

VOLUME 5

Frances Mather, Ph.D.

Associate Professor

Department of Biostatistics and Epidemiology

Tulane University

New Orleans, Louisiana 

Vickie M. Mays, Ph.D.

Department of Psychology

University of California, Los Angeles

Los Angeles, California 

Wendy McGoodwin

Council for Responsible Genetics

Cambridge, Massachusetts 

Rebecca A. Meriwether, M.D., M.P.H.

Director, Health Protection/Disease Prevention Division

National Institutes of Health

New Orleans, Louisiana 

Sybil Morial

Associate Vice President of Public Affairs 

and Communications

Xavier University of Louisiana

New Orleans, Louisiana 

Danita M. Muse, M.S.W.

Program Coordinator

Women With A Vision, Inc.

New Orleans, Louisiana 

Peter W. Nathanielsz, M.D., Ph.D., Sc.D.

James Law Professor of Reproductive Physiology

Director, Laboratory for Pregnancy and 

Newborn Research

Department of Physiology

College of Veterinary Medicine

Cornell University

Ithaca, New York 

Lawrence M. Nelson, M.D.

Staff Scientist and Senior Surgeon

Section on Women’s Health

Developmental Endocrinology Branch

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Cherie M. Nichols, M.B.A.

Chief, Planning Evaluation and Analysis Branch

Office of Special Populations

Office of the Director

National Cancer Institute

National Institutes of Health

Bethesda, Maryland 

Marcy Ouellette, M.D., M.P.H., T.M.

Medical Director, Women’s Health

Louisiana Office of Public Health

New Orleans, Louisiana 

Nancy Padian, Ph.D.

Associate Professor

Department of Gynecology and Reproductive Science

University of California at San Francisco

San Francisco General Hospital

San Francisco, California 

Eileen M. Palace, Ph.D.

Director, The Center for Sexual Health 

Associate Professor

Departments of Psychiatry and Neurology, 

Obstetrics and Gynecology, Urology, and Surgery

Tulane University School of Medicine

New Orleans, Louisiana 

Estella Parrott, M.D., M.P.H. 

Coordinator of Research Programs 

National Institute of Allergy and Infectious Diseases

Office of Research on Minority and Women’s Health

National Institutes of Health 

Bethesda, Maryland 

Elizabeth Rahdert, Ph.D.

Treatment Research Branch

Division of Clinical and Services Research

National Institute on Drug Abuse

National Institutes of Health

Rockville, Maryland 

Amelie G. Ramirez, Dr.P.H. 

Associate Professor, Associate Director

Center for Cancer Control Research

Baylor College of Medicine 

Houston, Texas 

Jayashree Rao, M.D.

Associate Professor, Department of Pediatrics

Louisiana State University Medical Center 

New Orleans, Louisiana 

Colonel Irene M. Rich, D.N.Sc. 

Director

Congressional Special Interest Research Programs 

U.S. Army Medical Research and Materiel Command 

Fort Detrick, Maryland 

B.J. Richardson, M.D.

Women’s College Hospital

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

C.B. Robinowitz, M.D.

Associate Dean, School of Medicine

Georgetown University School of Medicine 

Washington, District of Columbia

Adele Roman, R.N., M.S.W.

Deputy Women’s Health Coordinator

National Institute on Drug Abuse

National Institutes of Health

Rockville, Maryland 

Shirley B. Russell, Ph.D. 

Professor and Chair

Department of Microbiology

Associate Dean for Research

School of Dentistry

Meharry Medical College

Nashville, Tennessee 

Geri Scheller-Gilkcey, Ph.D.

Assistant Professor of Psychiatry and 

Behavioral Sciences, Medical School

Emory University

Atlanta, Georgia 

Valerie Setlow, Ph.D.

Director

Division of Health Sciences Policy

Institute of Medicine

National Academy of Sciences

Washington, District of Columbia

Meghan-Morgan Shannon, M.S.

Co-Coordinator

Medical Professionals/Persons with CFIDS/CFS/ME

Cardiff, California 

Amanda Sherman

President

DES Action USA

Oakland, California 

Denese Shervington, M.D., M.P.H. 

Institute of Women and Ethnic Studies 

New Orleans, Louisiana 

Linda C. Skidmore, M.S.

Director

Committee on Women in Science and Engineering

National Research Council

Washington, District of Columbia

Courtenay Smith

Editorial Assistant

Woman’s Day

New York, New York 

Sharilyn 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 

Ana Szarfman, M.D., Ph.D.

Medical Officer, Special Assistant to the Director 

of the Office of Epidemiology and Biostatistics

Center for Drug Evaluation

Food and Drug Administration

Rockville, Maryland 

Ramona Tascoe, M.D.

Chair

Council on the Concerns of Women Physicians

National Medical Association

Oakland, California 

Anita Corman Weinblatt, Ph.D.

Scientific Review Administrator

Division of Research Grants

National Institutes of Health

Bethesda, Maryland 

Judith Whalen, M.P.A.

Associate Director

Office of Science Policy, Analysis and Communication

National Institute of Child Health and 

Human Development

National Institutes of Health

Bethesda, Maryland 

Beth Willinger, Ph.D.

Director

Newcomb College Center for Research on Women

Tulane University

New Orleans, Louisiana 

Raymond Woosley, M.D., Ph.D.

Professor and Chairman

Department of Pharmacology

Georgetown University Medical Center

Washington, District of Columbia
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VOLUME 5

A

abuse

alcohol and other drug abuse 21, 26, 29, 36, 55,

61, 79, 81–84, 100

physical abuse 16, 18, 26, 55, 61, 77, 83–84

access to health care 5, 18, 57–58, 106

adolescence 15–17, 19–20, 91, 103

adverse drug reactions 67

alcoholism

treatment for 83

alternative medicine 13, 28

arthritis 35, 45–46, 49–50, 57–58, 60–61, 118

autoimmune disorders 26, 43–50

B

basic research 90, 92

behavioral factors in women’s health 5, 54, 80

biological clock 48

biological markers 19

breast implants 86–87

C

cardiovascular disease 23, 26, 33, 56, 74, 81, 95

career issues for women scientists 4, 72, 103

caregiving 33, 35–36, 59–60

childhood 11–12, 20, 74, 77, 91, 95, 103

chronic fatigue syndrome 116–117

clinical research 2–4, 20, 28, 91–92, 103, 106

clinical research

inclusion of women in 2–3, 21, 25, 27, 65, 71

contraceptive 23–24, 26, 46, 66, 102, 119

cost of health care 74–75, 80, 85–86

cultural issues 24, 32, 48–49, 54, 58, 60, 80, 

89–90, 101

culture and ethnicity 5, 89

D

depression 17–18, 26, 35–36, 44, 49, 55, 57–63, 

93, 102

diabetes 46, 56, 61, 74, 84, 91–92, 94, 118

diet 17, 20, 31, 33, 49, 74, 91–92, 94

diethylstilbestrol (DES) 3, 26–25, 28, 95, 118–119

disability 35–38, 58, 76

disease prevention 5, 36, 85, 100, 115

E

early detection and prevention 86

eating disorders 18, 54, 61, 91, 93

eduction

and outreach 84

professional education 28, 39, 90

patient education 12–13, 25–26, 39, 83, 91, 

96, 100, 114, 118

elderly 4, 35–39, 67, 85, 92, 106, 112

environmental issues

environmental exposure 13, 18, 21, 24, 

27–29, 72

epidemiologic research 27–29, 46, 74, 115

estrogen 31–33, 45–46, 67, 87, 92–93, 111–112, 119

ethical concerns 3, 14, 20

ethnicity 5, 12, 17, 32, 35, 54, 57, 60, 62, 89–90,

112, 116

exercise 17, 21, 31, 37–38, 60, 93

F

fertility 23, 28–29

fetal development 11

INDEX
132

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

G

gallbladder disease; gallstones 26, 75–76, 78

gastrointestinal disorders 26, 29

gender

gender differences iii, 4–5, 12–13, 18, 27, 29, 36,

39, 48–49, 54, 56–60, 62–63, 65–66, 72,

80–81, 91–92, 94, 103–04, 119

gender-based biology 46, 48

genetics 5, 14, 19, 28–29, 33, 38, 43–44, 57, 72, 85,

92, 94, 96, 110, 113–114, 116

H

headaches 55

health behaviors 17, 35, 54, 59–60

health information 24, 39, 88, 115

health promotion 33, 36, 38, 85, 88, 91, 115

health status iii, 5, 18, 35, 54, 56–57, 59–60, 

72, 80, 101, 124

high blood pressure (hypertension) 57, 61, 74, 

84, 94–95

hormones

hormone replacement therapy 38

I

immune function 50, 92

incidence 23–24, 26, 28, 43, 46, 49–50, 62, 75, 

81, 94, 97–98, 111

infancy 11, 110, 114

infant mortality 95, 102

infertility 23, 26, 28–29

inflammatory diseases 44–45

injuries 18, 23–24, 56

interdisciplinary studies 106

intervention strategies 100

irritable bowel syndrome (IBS) 26, 75–78

L

lifestyle 31–33, 36, 38, 56–57, 59–60, 80, 94, 114

liver disease 82

low birthweight 55, 95–97, 102

M

menopause 28, 31–33, 46, 66, 74, 91–94, 116

menstrual cycle 28, 48, 66, 91, 93

mental health 17, 20–21, 25–26, 37, 55–56, 61, 

78, 89–90, 102

minority women

African American 19–20, 31, 56, 61, 77, 80,

89–94, 98–100, 113

Asian 24, 31, 56, 95–96

Native Americans 24

N

networking 6, 107

nutrition 12–13, 15, 20–21, 38, 90–92, 94

O

obesity 21, 29, 32–33, 60, 74, 91–94

oral health 21

osteoarthritis 37, 57–58

osteoporosis 35, 37, 57, 116

outcomes

health outcomes iii, 4–5, 17, 19, 58, 72

P

pain 37–38, 49, 55, 75–76, 102, 112, 117

partnerships 26–27, 39, 104, 106, 116

perimenopause 32–33

pharmacologic differences

pharmacokinetics and pharmacodynamics of 

drug therapy 12, 65, 67, 119

physical activity 32, 74, 91, 96

physiological issues 38

postmenopause 32–33

posttraumatic stress disorder 26, 55–56, 78

pregnancy

teen pregnancy 15–17, 19

prenatal years 4, 10–13

preterm birth 95–97

prevention

preventive intervention 13, 29, 86, 100

prevention research viii, 13, 23, 26, 71, 115
133

VOLUME 5

psychiatric disorders 29, 55

psychological development 11, 13

psychosocial factors 60, 91

puberty 11–12, 15, 19–20, 48

public health services 5, 101

Q

quality of care 86

quality of life 32, 36, 39, 58, 60, 86, 106, 110, 112,

114, 119

R

rehabilitation 59–60, 75

reproductive health years 23, 25, 80, 101

research

biomedical iv, xx, 2–4, 6, 33, 59, 71, 85, 88, 

90, 104, 106, 119

behavioral iv, xx, 2–4, 6, 18, 26, 28–29, 32,

55–56, 59, 71, 80, 88, 92, 94

risk factors 28–29, 31, 36, 39, 74, 94, 96, 113, 116

risk-taking behavior 15–17, 26

rural women 80

S

sexual health 21, 102–103

sexually transmitted diseases (STDs) 16–18, 21,

23–24, 26, 55, 84, 98–102, 119

smoking 17–18, 21, 31, 33, 44, 60, 74, 88, 95

socioeconomic status 4–5, 24, 32, 35–36, 39, 60, 91

stress 12–13, 16–17, 26, 29, 33, 35, 37, 47, 49,

55–58, 60, 78, 92, 96

T

training 26, 32, 35, 38, 75, 83–84, 87, 106, 110, 113

U

urinary incontinence 26, 37–38

urinary tract infections 84

V

violence

domestic 26

W

weight control 32–33

wellness 11–13, 17, 100

135

VOLUME 5

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.

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NIH Publication No. 99-4389