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

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 1

EXECUTIVE SUMMARY
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 1. Executive Summary. Bethesda, MD. 

NIH Publication No. 99-4385, 1999.
On the brink of the new century, we face the exciting and unprecedented opportunity to understand

the functioning of our bodies and our minds to an extent that could not have been envisioned 100, 

or even 50, years ago. Along with a rapid pace of scientific discovery, the issue of women’s health 

has risen to prominence during the past decade in the broadest biomedical, political, and social sense. Our Nation

has recognized the importance of women’s health and, more specifically, the important contributions of culture, 

ethnicity, race, socioeconomic background, geographic location, and other social and economic factors to women’s

health status. We now understand women’s health as a reflection of multiple elements contributing to the overall

quality of women’s lives — and men’s lives — in the United States today.

After a year of intensive planning, the dream of a coordinated effort on women’s health at the National 

Institutes of Health (NIH) became a much-anticipated reality in September 1991 at a conference and series of

workshops in Hunt Valley, Maryland. Experts in the fields of basic and clinical sciences, practitioners interested 

in women’s health, and representatives of women’s organizations developed specific and workable recommendations to advance research activities on behalf of all the women, and thus of all the people, of the United States. 

Participants focused on research needs over the major divisions of a woman’s life span and the scientific issues, 

diseases, and impairments that might affect her health and well being during that life span. The deliberations 

and findings, published as Report of the National Institutes of Health: Opportunities for Research on Women’s Health,

stated a firm expectation as part of the introduction: “This research agenda, which will guide planning efforts at

NIH for the next several decades, is critical to improving the quality of life for all the Nation’s women.” That report

became the firm foundation and touchstone for the work of the Office of Research on Women’s Health (ORWH)

under its director, Dr. Vivian Pinn, whose appointment was announced at the September 1991 meeting.

During the past 7 years, ORWH at NIH has moved steadily and with confidence toward achieving the farreaching goals articulated in 1991. The Office has identified and assessed the enormous advances in basic and 

clinical science knowledge and linked them to a research agenda targeted to improve women’s health. There is 

now widespread, and largely unquestioned, recognition that researchers and clinicians must understand how differences in sex, gender, cultural, and ethnic and socioeconomic backgrounds may influence the causes, diagnoses,

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

progression, and treatment of diseases. The evolution, or perhaps even more, revolution in activities related to

women’s health, made the need for a reassessment of the agenda critical. An intensive series of workshops and

meetings, culminating in this new report, “Agenda for Research on Women’s Health for the 21st Century,” extend 

the vision of a comprehensive women’s health research agenda into exciting new directions and areas of research

endeavor not anticipated in 1991. The new challenge inherent to continuing progress in research on women’s

health is to establish sound scientific bases that will permit reliable diagnoses and effective prevention and treatment strategies for all women, from diverse cultural and ethnic origins, geographic locations, and socioeconomic

strata. The ultimate goal is to increase medical knowledge through sound research, which, thereby, will inform 

the development of policies and medical standards from which all women, and men, can benefit equally.

But, the guiding principle regarding women’s health research at NIH must remain and has remained

unchanged from its original ideal: that biomedical research must be targeted to all of the Nation’s women, 

of all races, all ages, and all socioeconomic and ethnic groups. Researchers must continue to make more 

intensive efforts to address the health needs of the whole woman — in body and in mind. As citizens 

of the United States and of the world, we cannot afford to do anything less.

Ruth L. Kirschstein, M.D.

Deputy Director, National Institutes of Health

Former Director, National Institute of General Medical

Sciences (1974-1993) and Acting Associate Director,

Office of Research on Women’s Health (1990-1991)
VOLUME 1

ACKNOWLEDGMENTS

During 1996 and 1997, the Office of Research on Women’s Health (ORWH) of the National Institutes

of Health (NIH), with the assistance of the Task Force on the NIH Women’s Health Research Agenda

for the 21st Century (Task Force) and the NIH Advisory Committee on Research on Women’s Health

(ACRWH), convened a series of three meetings at regional sites across the country and a final, national meeting 

to review NIH’s scientific agenda for research on women’s health issues. This series of meetings provided a forum

during which more than 1,500 scientists, clinicians, public policymakers, advocates, and members of the general

public examined the state of women’s health research at this point in history and discussed areas of emerging

importance for women’s health and biomedical research to develop a revised agenda that will address the 

changing public health and scientific needs and opportunities of the 21st century.

We are grateful to all who participated in these meetings and shared their knowledge, insights, concerns, 

and commitment to improving the health of women through the formulation of a coherent and comprehensive

agenda of basic and clinical biomedical and behavioral research. The recommendations made by participants 

at the four meetings will enable NIH to continue to foster and sustain multidisciplinary studies that address 

health and disease in girls and women across the life span.

This series of meetings would not have been possible without the assistance of a great many individuals,

including Ms. Joyce Rudick, the Acting Deputy Director of ORWH, who worked tirelessly in the planning, development, and organization of these meetings to review NIH’s agenda for research on women’s health. In this process,

NIH has benefited particularly from the contributions made by members of the NIH scientific community and 

by the Task Force on the NIH Women’s Health Research Agenda for the 21st Century. ORWH has been fortunate 

to have representatives of the NIH community, as well as women’s health advocates, scientists, and health professionals from across the country, serve as members of this important Task Force. We owe a special debt of gratitude

to the cochairs of the Task Force, Dr. Donna Dean and Dr. Marianne Legato, who also shared in chairing each 

of the meetings. Dr. Dean, who was Director of the Division of Physiological Systems within the NIH Center 

for Scientific Review at the time that these meetings commenced and currently serves as Senior Advisor to the

Deputy Director of NIH, is a member of the Coordinating Committee for Research on Women’s Health (CCRWH), 

the advisory body composed of the Directors or designated representatives of NIH’s institutes and centers (ICs). 

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

In addition, she is cochair of the CCRWH Research Subcommittee, which on behalf of the ICs assists ORWH 

in setting priorities for research and developing programs to implement such priorities. Dr. Marianne Legato, 

Professor of Clinical Medicine at Columbia University College of Physicians and Surgeons, is a charter member 

of the ACRWH, the body of 18 distinguished physicians, academicians, practitioners, scientists, and other individuals whose clinical practice, research specialization, or professional expertise includes a significant focus on

research on women’s health, and who provide guidance and direction to ORWH and its policies and programs. 

In addition to those who served on the Task Force, ACRWH, and CCRWH, many others have assisted 

ORWH in these meetings and have played important roles in women’s health over the years. ORWH and all who 

are active in the movement to improve the health of women must also acknowledge the foresight of Dr. Edward 

N. Brandt, a charter member of ACRWH, who established the first Public Health Service Task Force on Women’s

Health in 1983, sparking a new level of Federal commitment to addressing women’s health issues. This commitment was sustained by Dr. James Mason, Assistant Secretary for Health, by Dr. Audrey Manley, former Deputy

Assistant Secretary for Health, and by Dr. William Raub, who, as Acting Director of NIH, established ORWH in

September 1990. Dr. Ruth L. Kirschstein, who served as the first and continuous cochair of the PHS Coordinating

Committee on Women’s Health Issues from 1983 until 1995, has a long history of activism on behalf of women 

in biomedical science and women’s health research; she served as the first Acting Director of ORWH and has continued to provide invaluable guidance and support to ORWH in her present position as Deputy Director of NIH.

ORWH and other efforts of the Federal Government to improve the health of women have greatly benefited 

from the support and interest of many members of the U.S. Congress, as well as the Executive Branch. Important impetus and support for efforts to improve the health of women and NIH’s process of reviewing the research

agenda on women’s health have been provided by the Secretary of the Department of Health and Human Services, 

Dr. Donna Shalala. This support was also evidenced by the presence of Senator Barbara A. Mikulski, Congresswoman Connie A. Morella, Congresswoman Louise M. Slaughter, a representative of Congressman Louis Stokes,

and the Director of the White House Office for Women’s Initiatives and Outreach, Audrey Tayse Haynes, 

at the final national meeting, “Putting It All Together: The Agenda for Research on Women’s Health for the 

21st Century,” held in November 1997. We gratefully acknowledge their support and contributions in helping NIH to chart a bold plan of action for improving the health of women in the next millennium.
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ORWH wishes to acknowledge and thank the working group cochairs of the meetings held in Philadelphia,

New Orleans, Santa Fe, and Bethesda, as well as the people who served on committees and working groups and

who contributed their collective expertise to the creation of the Agenda for Research on Women’s Health for 

the 21st Century.

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 1

COCHAIRS

Donna Dean, Ph.D.

Senior Advisor to the Deputy Director

(formerly, Director, Division of Physiological Systems

Center for Scientific Review)

National Institutes of Health

Bethesda, Maryland

Marianne Legato, M.D.

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

Edward Brandt, M.D., Ph.D.

Regents Professor and Director

University of Oklahoma, Center for Health Policy

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma

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

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

Hazel Harper, D.D.S.

President, National Dental Association

Washington, District of Columbia

Joseph Hurd Jr., M.D.

Chairman, Department of Gynecology

Lahey Hitchcock Clinic Medical Center

Burlington, Massachusetts

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

Chief of Surgical Oncology

North Shore University Hospital

Manhasset, New York

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

Professor and Chair

Department of Community Health Sciences

Tulane University Medical Center

School of Public Health and Tropical Medicine

New Orleans, Louisiana

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

Distinguished Professor and Dean

Indiana University School of Nursing

Indianapolis, Indiana

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

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.

Chief, Preventive Interventions Program

National Institute of Mental Health

National Institutes of Health

Bethesda, Maryland

David Robinson, Ph.D.

Program Director

National Heart, Lung, and Blood Institute

National Institutes of Health

Bethesda, Maryland

Helen Rodriguez-Trias, M.D.

Co-Director, Pacific Institute for Women’s Health

Western Consortium for Public Health

Los Angeles, California

Rosalie Sagraves, Pharm.D.

Dean, College of Pharmacy

University of Illinois at Chicago

Chicago, Illinois

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

Professor 

University of New Mexico School of Medicine

Albuquerque, New Mexico

Anne Sassaman, Ph.D.

Director, Division of Extramural Research and Training

National Institute of Environmental Health Sciences

National Institutes of Health

Bethesda, Maryland

Ora Lee Strickland, Ph.D.

Independence Professor

Nell Hodgson Woodruff School of Nursing

Emory University

Atlanta, Georgia

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

Chair, Council on the Concerns of Women Physicians

Kaiser/National Medical Association

Oakland, California

Constance Weinstein, Ph.D.

National Heart, Lung, and Blood Institute (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

Members-at-Large

Coordinating Committee on Research on Women’s 

Health Members

Advisory Committee on Research on Women’s

Health Members
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iii

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .v

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

Overview and Perspectives from the Task Force Cochairs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

The Use of “Sex” and “Gender” To Define and Characterize Meaningful 

Differences Between Men and Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Summary Reports of the Working Groups

Reports of the Working Groups: Scientific Chapter — Summary of Recommendations

Alcohol, Tobacco, and Other Drug Use, Disorders, and Consequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

Behavioral and Social Sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

Bone and Musculoskeletal Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

Digestive Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37

Immunity and Autoimmune Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41

Infectious Diseases and Emerging Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43

Mental Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .47

Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .51

Oral Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53

Pharmacologic Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .57

Reproductive Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63

Urologic and Kidney Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67

Reports of the Working Groups: Sex and Gender Perspectives Throughout 

the Life Cycle — Summary of Recommendations

Prenatal, Infancy, and Childhood Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71

Adolescent Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73

Reproductive and Middle Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .75

Perimenopausal and Postmenopausal Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79

Elderly and Frail Elderly Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .81

Reports of the Working Groups: Differences Among Populations of Women 

Throughout the Life Cycle — Summary of Recommendations

Prenatal Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .87

Infancy and Childhood Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .89

Adolescent Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .93

Reproductive and Middle Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95

Perimenopausal Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .99

Postmenopausal Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101

Elderly and Frail Elderly Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .105

Career Issues for Women Scientists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111

CONTENTS

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

Selected Issues in Research Design

Health of Special Populations of Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117

Sex and Gender Differences in Clinical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119

Racial, Ethnic, and Cultural Diversity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .121

Multidisciplinary Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .123

Selected Topics in Health Impact and Health Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127

Crosscutting Issues and Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135
REVISITING THE NIH RESEARCH

AGENDA ON WOMEN’S HEALTH

FOR THE 21 S T CENTURY: 

A COLLABORATION BETWEEN

NIH AND THE BROADER

WOMEN’S HEALTH COMMUNITY

As the National Institutes of Health (NIH)

Office of Research on Women’s Health

(ORWH) engages the scientific, health care,

public policy, advocacy, and other communities in a

review and revision of the NIH research agenda on

women’s health for the 21st Century, it is salutary to

examine the history of efforts to improve the health 

of women through research, and the steps that led 

NIH to the landmark series of four scientific workshops held in 1996 and 1997.

There is no question that research is central to 

providing the scientific foundation for changes and

improvements in health practices and policies. Expanding our understanding of normal and abnormal biologic processes and behavior can result in improved

prevention, diagnosis, and treatment of diseases, disabilities, and other conditions that affect the health of

women and their families. Yet, despite the importance

to the United States of improving the health status of

women across the life span, the emergence of women’s

health issues among our nation’s priorities did not

occur overnight. We owe much of the increased focus

of the scientific community on women’s health to many

individuals, groups, and organizations that have been

working to improve the health of women for some

time. These include the Boston Women’s Health Book

Collective, the National Women’s Health Network, the

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INTRODUCTION

National Black Women’s Health Network, the Society 

for the Advancement of Women’s Health Research, 

and many others, some of whom provided testimony

during our public hearings. For many years, these

organizations have been working “in the trenches,”

calling attention to the need to focus our attention 

on women’s health. Nevertheless, only in recent years

has the Federal Government recognized women’s

health as a real issue requiring a real remedy. Today,

thanks to the efforts of advocates and scientists in 

and outside the Federal Government, we are beginning to make progress.

PHS Task Force and Establishment of ORWH

In 1983, the Assistant Secretary for Health, 

Dr. Edward N. Brandt, Jr., 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. 

In a report published in 1985, this Task Force made 

a number of recommendations on a broad array of

women’s health issues relevant to the entire life span 

of girls and women. At that time, Dr. Brandt stated, 

“I am committed to seeing that this report results in

action that is beneficial to the women of America.”

Among the most pertinent recommendations of the

Task Force report was one that said that “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.”

Following publication 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. Two years later, in 1987, the policy was

incorporated into and published in the NIH Guide 

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
At the same time, Dr. Raub stated that “The new

Office will have the authority and responsibility to act

with and on behalf of the NIH Director to monitor 

and coordinate the activities of the constituent ICDs 

at NIH in regard to research on women’s health . . .”

With these words, ORWH was established and

given the broad mission that still directs the activities 

of the Office today. This mission encompasses:

• Establishing NIH-wide goals and policies for

research related to women’s health.

• Developing a plan to increase NIH-supported

research on women’s health, then implementing

and monitoring its effects.

• Coordinating NIH activities undertaken in performing women’s health research.

• Providing advice and staff support to the NIH

Director and senior NIH staff regarding the 

overall direction of and approaches to NIH 

programs of research related to women’s health.

• Interacting with the scientific and medical 

communities, organizations with an interest 

in women’s health, and other components of 

government to inform them of NIH programs 

related to women’s health.

• Developing special initiatives to increase the 

participation of women as subjects in clinical

research and of institutions and investigators 

in performing research on women’s health.

One of the earliest announcements of activity 

by this new office was made on that same September

day by Dr. Ruth L. Kirschstein, who promised that 

“. . . As one of its most important activities, the 

Office, this fall, will convene a planning group to 

prepare the background for a major conference 

which will serve to set an agenda for NIH research 

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

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.

In 1990, the Congressional Caucus for Women’s

Issues requested that the U.S. General Accounting

Office (GAO) study NIH’s implementation of the guidelines for inclusion of women. The resulting GAO report

stated that the implementation of the policy for the

inclusion of women was slow and not well communicated, gender analysis was not implemented, and the

impact of policy could not be determined.

In September 1990, just 3 months after the release

of the GAO findings, the subsequent media coverage

and public reaction catalyzed NIH to establish the

Office of Research on Women’s Health. The office was

set up by Dr. William Raub to serve as the focal point

for women’s health research at NIH, working in a collaborative partnership with NIH’s institutes and centers

(ICs). ORWH was announced at an NIH roundtable

meeting with representatives of the Congressional 

Caucus on Women’s Issues on September 10, 1990. A

press release from the U.S. Department of Health and

Human Services at the time of this meeting stated that:

ORWH is charged with assuring that

research conducted and supported by NIH

appropriately addresses issues regarding

women’s health and that there is appropriate

participation of women in clinical trials . . .

The Office will establish NIH-wide goals and

policies for research related to women’s health.

It will also coordinate NIH activities undertaken in performing such research. Finally, 

the Office will interact with the scientific and

medical communities, organizations with an

interest in women’s health and other components of government to inform them of NIH’s

programs related to women’s health, identify

areas of research that need emphasis and

involve them in efforts to expand and 

encourage research on women’s health.
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As a result, 1 year later, in September 1991,

ORWH held public hearings and a scientific workshop at Hunt Valley, Maryland, to set NIH’s agenda 

for research on women’s health issues. The report 

from that meeting, Report of the National Institutes of

Health: Opportunities for Research on Women’s Health,

commonly referred to as the Hunt Valley Report,

served as the basis for NIH’s research priorities 

in women’s health for 7 years.

At the Hunt Valley meeting, discussions centered

around life span concepts for women’s health and

crosscutting areas of science. These included:

Life Span

Birth to Young Adulthood

Young Adulthood to Perimenopausal Years

Perimenopausal to Mature Years

Mature Years

Crosscutting Science

Reproductive Biology

Early Developmental Biology 

Aging Processes 

Cardiovascular Function and Disease

Malignancy

Immune Function and Infectious Diseases

In addition, speakers addressed morbidity and

mortality in women, ethical and legal issues, women 

as research subjects, and women in biomedical careers.

Thus were launched the programs of ORWH to

“expand and encourage” research on women’s health.

In 1993, ORWH was legislatively mandated in the NIH

Revitalization Act. Women’s health research at NIH is 

a partnership between ORWH and NIH institutes and

centers. During the past 7 years, ORWH’s responsibilities and major program efforts have increased and,

while there is still a lot to be done, we have made 

some progress.

NIH Mandate for the Inclusion of Women and 

Minorities in Clinical Research

The establishment and implementation of policies

for the inclusion of women and minorities in clinical

research funded by NIH has its origins in the response

to the PHS Task Force on Women’s Health Issues and

in response to the GAO report of 1990. 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, the Congress made what had previously been policy into Public

Law, through a section in the NIH Revitalization Act 

of 1993 (Public Law 103-43), 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:

• NIH must ensure that women and minorities and

their subpopulations be included in all human 

subject research;

• Women and minorities and their subpopulations

must be included in phase III clinical trials in

numbers adequate to allow for valid analyses 

of differences in intervention effect;

• Cost is not allowed as an acceptable reason 

for excluding these groups; and,

• NIH must 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, and they have been fully

implemented. It is now the policy of NIH that 

women and members of minority groups and their
4

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

subpopulations must be included in all NIH-supported

biomedical and behavioral research projects involving

human subjects, unless a clear and compelling rationale

and justification establishes that inclusion is inappropriate to the health of the subjects or the purpose of

the research.

Working in collaboration with the Office of Extramural Research and other components of NIH, we have

established a tracking system to monitor inclusion.

Indeed, for the first time in NIH’s history, we are able

to determine the numbers of women and minorities 

in clinical trials, and we are now beginning to analyze

data to establish trends in inclusion and determine 

better ways to examine these data. Thus far, we have

found high compliance with inclusion policies.

The goal of NIH policy is not to satisfy any quotas

for proportional representation, but rather to conduct

biomedical and behavioral research such that the scientific knowledge acquired will be generalizable to the

entire population. In response to the tragedies of the

PHS syphilis study in Tuskegee, Alabama, and the

effects on those exposed to DES and thalidomide in

utero, regulations were put in place to protect women,

minorities, and other populations from being exploited

in research. As we work to ensure women’s appropriate

inclusion in clinical studies, we still must grapple with

the very sensitive ethical and legal issues of including

women of childbearing age in such research. In addressing these issues, we must weigh the risks of such participation to women and their potential offspring against

the benefits of participation in clinical studies.

A continued emphasis on the need for innovative

and successful strategies to recruit women as volunteers in clinical research, including special populations 

of women across the life span, must remain a consideration in research design. In fact, 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.

Women in Biomedical Careers

With expanding horizons in science and biotechnology, greater participation by women as investigators

in studies to explore new frontiers of knowledge about

health, disease, and normative development in girls

and women is needed. While exact figures are not

available for those who are participating in research,

there is a need to increase not only the numbers of

women who are biomedical and behavioral investigators, but also the numbers of women who are in policy

making positions and who can influence or determine

the direction of research initiatives.

To help us to determine the best ways to increase

opportunities for women in biomedical research

careers, in 1992, ORWH convened a public hearing

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

The goal was not only to identify barriers to women’s

success, but also to devise strategies and programs 

to enable women to overcome those barriers.

At the 1992 meeting, a number of barriers were

identified and published in a report, Women in Biomedical Careers: Dynamics of Change — Strategies for 

the 21st Century. From nearly 70 testimonies, 9 general

issues that present barriers emerged. These barriers 

are common to women in the biomedical professions

regardless of racial, ethnic, cultural, socioeconomic, 

or other backgrounds. 

• Recruiting women to biomedical sciences;

• Visibility, role models, and mentors;

• Career paths and rewards;

• Re-entry into a biomedical career;

• Family responsibilities;

• Sexual discrimination and sexual harassment;

• Research initiatives on women’s health;
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VOLUME 1

• Sensitizing men about special career concerns 

of women; and

• Minorities and racial discrimination.

Based on the findings and recommendations of

that meeting, ORWH has initiated and sponsored a

number of programs, including one that addresses the

loss to science of women who have interrupted their

research careers to fulfill familial responsibilities, the

Re-entry Program for Biomedical Scientists. Started 

as a pilot project in 1992, the re-entry program was

assessed under the leadership of Joyce Rudick and 

the cochairs of the Subcommittee on Biomedical

Careers of the NIH Advisory Committee on Women’s

Health Issues, Dr. Anne Sassaman and Dr. Julia 

Freeman. The re-entry program has now been institutionalized across NIH. Since 1992, participants 

in the program have published 72 papers, with 43 

re-entry scientists as the primary author, in such 

journals as the Journal of Cell Science, Biological Psychiatry, Molecular Microbiology, American Journal of 

Epidemiology, Journal of Biological Chemistry, American

Journal of Psychiatry, Journal of Clinical Investigation,

and Journal of the American Medical Association.

Ensuring that the findings derived from research

on women’s health are incorporated into the education and training of the next generation of health care

providers is an important priority for ORWH. As a 

part of our effort to address the implementation of the

NIH agenda on women’s health research and the role 

of such research in helping to establish improved standards of health care practice that promote 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 women’s health in their curricula.

The resulting report, Women’s Health in the Medical School

Curriculum: Report of a Survey and Recommendations,

also contains examples of curricula that incorporate

women’s health issues. We are now working with 

the dental, nursing, and pharmacy representatives 

for a similar study of their educational curricula.

We have also put in place a number of other 

programs and initiatives to enhance participation of

women and men scientists in research on women’s

health. These include workshops on how to speak 

and write about science, as well as training projects

that provide opportunities for high school students,

college faculty and students, and minority students 

to obtain research experience or exposure to current

scientific concepts through NIH. ORWH has also

developed and supported a number of programs 

for the advancement of girls and women in science

through collaboration with the NIH Office of Science

Education. These programs include: outreach on 

the World Wide Web; a speakers bureau that allows 

a diverse group of women scientists in the NIH community to provide both role models and information

about careers in research; a very popular course designed to teach young scientists to write about science

effectively; a series of workshops to teach young scientists how to present scientific data effectively; a program for NIH summer interns that provides a forum

for discussion of family and career concerns that can

affect their professional and personal lives; and a series

of workshops to support the successful career development of young postdoctoral intramural researchers.

NIH National Research Agenda on Women’s Health

Progress has been made in establishing women’s

health research as an integral part of the fabric of 

NIH research and programs; but progress gives rise 

to new questions, a need for an assessment, and 

a consideration of new priorities and a revitalized

research agenda. We believed that it was time to 

look “beyond Hunt Valley” and to update our agenda.

Beginning in September 1996, ORWH convened a

series of meetings, “Beyond Hunt Valley: Research 

on Women’s Health for the 21st Century,” to foster 

collaboration among representatives of the NIH 
6

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

community and the broader women’s health community to revise the research agenda on women’s health.

In planning these meetings, we turned to the model 

of the first Hunt Valley meeting where broad participation through public hearings and workshops proved so

productive and fruitful. This mechanism has provided

an opportunity for ongoing collaboration among individuals and 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.

The original women’s health research agenda

developed as a result of the Hunt Valley meeting

embodied certain underlying principles that will 

continue to inform our directions for the future. 

The Hunt Valley report redefined the parameters 

of women’s health to encompass research to better

understand 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 in the past. 

This 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 an expanded

concept of women’s health and research that encompasses the health of girls and women across the life

span, from the prenatal stage to that of the frail elderly.

Most important, the agenda reflects the fact that

women’s health implies more than the reproductive

system. The agenda also emphasizes basic science

investigations, not just human subject research.

The research agenda includes biomedical as well 

as behavioral and psychosocial research, with a focus

on multidisciplinary collaboration. It 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

diverse populations of women. Moreover, priorities

have been established for populations of women and

girls that have been previously excluded from scientific

investigation, such as minorities, women of low socioeconomic status and isolated geographic locations, 

lesbians, and women with disabilities.

In all our efforts to implement our research 

agenda, ORWH participates in an active and beneficial partnership with all of NIH’s institutes and centers. We continually review our research priorities to

determine where the major gaps in knowledge exist.

At our first regional meeting, held September 1996

in Philadelphia, where our hosts were the Allegheny

University of the Health Sciences and the University 

of Pennsylvania, we started to examine our research

agenda to ensure its relevance as we move toward the

next century. At the Philadelphia meeting, we directed

attention to some of the major areas of concern for

women’s health. We later looked at women’s health

from two perspectives — sex and gender factors, as

well as differences in health among diverse populations of women. At the second meeting, held in New

Orleans, we examined aspects of the research agenda

based upon sex and gender perspectives (i.e., physiological, psychosocial, and pharmacologic differences

between women and men). Plenary presentations

addressed the role of hormones in sex and gender 

differences, as well as the role of the environment and

genetic heritage. At our third regional meeting, held 

in Santa Fe, New Mexico, participants focused on factors that contribute to differences in health status and

health outcomes among diverse populations of women.

These included biological, genetic, racial, cultural and

ethnic, psychosocial and behavioral factors, educational

influences, traditional and alternative health practices,

environmental influences, poverty and socioeconomic

status, access to health care, and occupational issues.

The plenary sessions also included considerations of

health issues for women who have disabilities.
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At the final, national meeting in the series, 

held in Bethesda, Maryland, in November 1997, 

we addressed issues raised at the three regional 

meetings and invited participants to consider additional issues to guide our Task Force in developing 

recommendations for the NIH research agenda on

women’s health for the 21st century. The specific 

objectives of this final workshop were to:

• Consider progress in knowledge about 

women’s health through research;

• Determine continuing or emerging gaps 

in knowledge, and related issues and 

implications;

• Recommend a new framework for 

research priorities on women’s health, 

conditions, and diseases;

• Recommend how these research 

initiatives can best be accomplished;

• Recommend ways to improve dissemination of research outcomes, integration 

into health education, and implementation in health practices and public 

policies; and

• Recommend programs and collaborations to increase opportunities for 

participation and advancement of 

women in research careers.

We asked participants to consider 

the following:

• The original Hunt Valley report 

recommendations;

• Deliberations and recommendations 

from the three regional meetings;

• Special populations of women;

• Factors that affect different populations 

of women;

• Sex and gender issues;

• Normal processes, developmental 

biology, and aging; and

• Life span concepts.

All the recommendations for our research agenda

must be based upon science driven initiatives. Thus,

the role of the participants was challenging, significant,

and meaningful. Our updated agenda must reaffirm the

commitment to an integration of scientific disciplines

and medical specialties with advocacy and forwardthinking optimism. The goal is to make a positive difference in women’s health in the 21st century through

an improved research agenda that will yield scientific

data to lessen or eliminate continuing or emerging 

gaps in knowledge about women’s health.

During the past decade, 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 from the scientific and lay

communities, as we enter the 21st century, ORWH 

can build on that progress and markedly improve the

health of women and their families. That is the vision

for women’s health in the United States and worldwide

that we have entrusted the members of the Task Force

and all participants in this process to help us ensure for

the future. No single individual or group can do the

job alone. The challenge — and the responsibility —

must be shared by all of us.

The 7 years since the Office of Research for

Women’s Health’s (ORWH) original report on

the health needs of women have witnessed a

remarkable expansion of interest in the female patient.

In a very real sense, that interest is the result of the

expanding competence and power of women that

began with World War II. This global catastrophe facilitated women’s entries into positions and professions

that had been previously almost exclusively available 

to men. The emergence of feminism in the 1950s was 

an inevitable consequence of women’s new sense of

what was possible for them to achieve on their own

rather than through alliances with powerful men:

access to the professions and to their own money, 

and with it, increasing immediate control over the

world around them. Feminism was bred of women’s

new and expanded sense of their identities as individuals beyond their traditional roles of wife and 

mother, and of what they were due from a society 

that held them as less valuable than men. Their 

interest in social justice and appropriate access to the

options available within the life of the community

extended to a consideration of their health needs.

Women’s increasing ability to call attention to 

their needs gained strength in the decades after World

War II and was reflected first in the 1985 report of the

U.S. Public Health Service’s Task Force on Women’s

Health Issues, which concluded that women’s health

care was compromised by the lack of research focus on

women’s health concerns. By 1986, the National Institutes of Health (NIH) urged that research protocols

include appropriate numbers of female subjects wherever relevant, although the 1990 report of the General

Accounting Office (GAO) indicated that because of a

lack of aggregate or NIH-wide recordkeeping, it was

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VOLUME 1

OVERVIEW AND

PERSPECTIVES

FROM THE TASK

FORCE COCHAIRS

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

Professor of Clinical Medicine

Columbia University College of 

Physicians and Surgeons

Donna Dean, Ph.D.

Senior Advisor to the Deputy Director

National Institutes of Health

unable to monitor NIH’s performance on ensuring that

this was accomplished. This report and other pressures

for more attention prompted the NIH Revitalization

Act of 1993, which stated the condition that any NIHsupported research must include appropriate numbers

of subpopulations (including women) in the cohort of

subjects studied. Cost was not a justification for failure

to do this. In 1990, the Congressional Caucus on

Women’s Issues introduced 22 bills to Congress that

addressed research, care, and prevention issues in

women’s health. Six of the research-related provisions

were incorporated into the 1991-1992 NIH Revitalization Act, which became law in 1993 and gave statutory authorization to ORWH. The Food and Drug

Administration (FDA) was not exempt from the sweeping reforms. In 1992, FDA cosponsored a conference

with the Food and Drug Law Institute to debate issues

of including women in clinical trials of FDA-regulated

products. The GAO released a report examining FDA’s

policies and the pharmaceutical industry’s practices

regarding drug testing and women and concluded that

for more than 60 percent of the drugs, the representation of women in the test population was less than the

representation of women in the population with the

corresponding disease. The worst case, ironically, was

in the area of cardiovascular disease, where companies

were frequently failing to analyze or collect data for

gender differences in response to drugs. By 1993, FDA

lifted its 1977 edict that reproductive-age women

should be isolated from clinical research and recommended that data be analyzed as a function of gender.

Women have demanded to learn more about the

normal physiology of females and of the unique ways 

in which they experience disease. They want to be

included in clinical investigations, they want federal
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

monies devoted to their health needs, and they have

been entering medical and other health professional

schools in increasing numbers. Clinical researchers

have concentrated on exposing, publicizing, and 

correcting gender prejudice in health care delivery 

to women. The results have been mixed, but women

have achieved some progress. A notable example is the

Women’s Health Initiative (WHI), an unprecedented

prospective $625 million study on 165,000 women of

diverse racial and ethnic backgrounds between the ages

of 50 and 79 years of age in large and small communities nationwide. During the past few years, ORWH has

flourished, using its resources to focus on and publicize

women’s health needs, to support research that concentrates on women, and to ensure ways to encourage

women’s entry into and retention in research careers.

This Task Force had several fundamental questions about women’s health, some of which had been

addressed by the Institute of Medicine’s Committee on

the Ethical and Legal Issues Relating to the Inclusion 

of Women in Clinical Studies. Because of the lack of 

a tracking system to monitor inclusion in 1990, that

committee had difficulty in demonstrating that women

had been understudied or excluded from research.

Nevertheless, the report made it clear that investigators frequently did not report the results of data 

analyzed by sex and gender, did not perform any 

sex and gender analyses of study results, and did 

not recruit adequate numbers of women to support 

conclusions regarding the impact of sex and gender 

on the observations made. 

Several fundamental questions arise, some of

which have not yet been answered satisfactorily.

• Has the exclusion of women from clinical 

research affected their health?

We are just beginning to understand and appreciate the differences between men and women in virtually

every system of the body, as well as in the way men

and women experience disease. Differences in drug

metabolism frequently explain women’s vulnerability 

to medications that have been tested primarily in men.

For example, one study reports that the treatment of

mild to moderate hypertension in Caucasian women

increased the all-cause death rate by 26 percent, while

lowering all-cause mortality in men by 15 percent.

Another study (SWORD trial on sotalol in the treatment of postmyocardial infarction arrhythmias) was

discontinued because of the increase in mortality 

of women in the trial.

• Can research on men be extrapolated to women

without modification?

Investigators consistently assume that information they glean from clinical and basic studies 

on male subjects can be extrapolated without modification to women. This traditional assumption was

rarely, if ever, directly tested. It is remarkable that 

we have tolerated this “leap of faith” in an otherwise

rigorous research enterprise. In no other area have 

we permitted unproven assumptions to be accepted 

as fact. We now have enough information about the

differences between males and females to acknowledge the danger of assuming that they are identical. 

An excellent example is the way in which men and

women respond to drugs: The working group on 

pharmacologic issues has highlighted the differences

between men and women in the cytochrome P450 system and the unique role of hormones in drug effects.

• Do government mandated research guidelines to

include women restrict the scientific community 

so severely that they compromise the quality and

amount of investigation done? What does it cost 

to include women in clinical investigation? If it 

is more, will the result be fewer clinical trials and

studies? If so, what will be the impact on the

health of the public?

Some diseases occur more frequently in men

than in women, or during a quite different age or

developmental period. Those factors, as well as the 

difficulty in recruiting premenopausal women, have

been cited as impeding clinical investigations that

include both males and females. The scientific community has defended its reluctance to study women
11

VOLUME 1

directly on the basis of the relatively more constant

physiologic state of males. Complicating the issue is 

the cyclic variability of women of reproductive age.

Including younger females in clinical trial populations

would necessitate larger and, therefore, more costly

investigations. Regardless of the assertion that cost

should not be an obstacle to creating an adequate and

accurate protocol, these economic, ethical, moral, and

intellectual issues need public debate and clear guidelines. The assumption that studies on men are “good

enough” for women, based on the premise that to be

human is a homogeneous condition, is flawed. We

have not, however, acknowledged the fact that, so 

far, our attention has been concentrated on postmenopausal women in the major studies devoted to the

female patient (e.g., the Postmenopausal Estrogen/

Progesterone Intervention [PEPI] study and the WHI).

The unique needs of the premenopausal and pregnant

woman must be considered as well. The vulnerability

of the premenopausal woman, particularly if she is

pregnant, has often been cited as a reason for exclusion from clinical studies and trials of younger females.

This general policy of protectionism, codified in PHS

regulations promulgated by the Office for Protection

from Research Risks (OPRR), characterized FDA and

NIH standards for clinical trial populations from the

1970s until the late 1980s. As a direct result, we have

been left ignorant of much essential first-hand information about the female patient and her unique

responses to therapeutic interventions developed 

in studies carried out exclusively in men.

The issue of how to describe differences in health

status or outcomes between men and women is fraught

with conceptual difficulty. Should differences — for

example in rates of heart disease, participation in research, or access to specialty services — be attributed

to “sex” or to “gender”? Are the two terms equivalent,

or do they describe conceptually distinct approaches to

understanding difference? Unfortunately, the language

of difference in the biomedical literature is often imprecise, conflating the two terms, treating them as 

virtual synonyms. This imprecise use of language presented difficulty to the Beyond Hunt Valley working

groups and Task Force and remains a challenge.

Hence, we wish to acknowledge the significance 

of the conceptual distinction for women’s health. The

Task Force in no way wishes to imply that straightforward biological difference, such as that associated with

the action of a particular sex hormone, is an adequate

explanatory model for research on health differences

between men and women. Since confusion is the order

of the day throughout the biomedical literature, it is

impossible within the confines of this report to offer a

definitive clarification. Readers will note that authors

differ in their use of the terms, with some maintaining 

a clear distinction between biological versus social or

cultural elements of difference and others using the

terms as virtual synonyms. Ideally, a women’s health

research agenda would recognize the need for studies

on all aspects of differences between men and women,

maintaining the conceptual clarity necessary for high

quality research. During the next 5 years, ORWH will

take on that challenge as well. An excellent conceptual

framework is presented in the section of this report 

on sex and gender terminology (see page 15). 

BASIS OF REPORT 

RECOMMENDATIONS

The chapters of this report present the recommendations of the 1997-1998 Task Force for Beyond

Hunt Valley: Research on Women’s Health for the 21st

Century, appointed by ORWH to determine the most

fruitful and useful directions for medical research conducted by NIH on women during the next 5 years.

Current NIH Research of Particular Importance 

to Women

Mindful of the rich and varied portfolio of 

research efforts already supported by NIH, the Task

Force first reviewed current NIH-supported activities

and research of particular importance for women.

Some examples of major ongoing investigations 

at NIH are as follows:

1. Neurosciences and brain biology. Given the sexual

dimorphism in the structure and function of the

human brain, as well as in the incidence of degenerative and affective diseases of the brain, 
12

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

the following areas of ongoing research promise to

be particularly useful for women: (a) the development

and degeneration of neurons; (b) the therapeutic

effects of St. John’s Wort; (c) the nature of pain; 

(d) behavioral research on obesity and substance

addiction (including smoking); (e) development 

of new drugs for the treatment of alcoholism and

drug addiction; and (f) the brain molecular anatomy project, which studies the patterns of gene

expression and the role of single genes in brain

function of mice with altered genomes.

2. Cardiovascular disease. The phenomenon of why

many aspects of the risk factors for, clinical presentation of, testing modalities of, therapeutic choices 

of, and outcomes of cardiovascular disease are 

different for men and women has been explored

extensively by cardiovascular experts during the

past decade. The following gender-specific studies

are of particular interest to women: (a) the role 

of hypertension in accelerating vascular disease; 

(b) the role of plaque in atherosclerosis and the

mechanism of how it is formed; and (c) the role 

of genes in progression and experience of diseases 

of the heart and blood vessels, particularly regarding the involvement of other organs.

3. Asthma. The prevalence of asthma in women, particularly in Hispanic females, makes it a disease 

of particular interest to clinicians interested in

treating the female patient. Clinical trials to prevent environmentally induced asthma in children

are of special interest to women. The prevention 

of asthma in children is an area of heavy concentration at NIH, particularly the prevention of 

morbidity and mortality by monitoring trends 

and risk factors for this disease.

4. Infectious diseases. Infectious and parasitic diseases

still claim more lives than any other disease category in the world. Research relevant to women

includes (a) the search for novel approaches for 

the treatment of infectious diseases, particularly

tropical and viral diseases, tuberculosis, and 

hepatitis C; and (b) work on the genome of the

AIDS virus, which has offered expanding promise

for development of effective therapy and serves 

as a model of how genetic information may help

defeat disease.

5. Diabetes. Diabetes poses particular problems 

for women, not the least of which is the fourto sixfold increase in vulnerability of the diabetic

woman, regardless of age and menopausal status,

to coronary artery diseases. Hence, the following

investigations are of particular importance: (a) the

role of nutrition and obesity in the pathogenesis 

of diabetes; (b) efforts to effect the regeneration 

of insulin producing cells; (c) the development 

of enhanced methods for drug delivery; and 

(d) research into the pathogenesis of the various types of diabetes.

6. Women’s Health Initiative. The Women’s Health 

Initiative (WHI), one of the largest primary prevention studies in postmenopausal women in the

United States has three components: (1) a randomized controlled clinical trial (67,000 participants)

that will evaluate the effect of a low-fat diet on prevention of breast and colon cancer and coronary

heart disease, examine the effect of hormone

replacement therapy on prevention of coronary

heart disease and osteoporotic fractures, and 

evaluate the effect of calcium and vitamin D 

supplementation on prevention of osteoporotic

fractures and colon cancer; (2) an observational

study (100,000 participants) that will delineate

new risk factors and biological markers in women

and identify predictors of disease; and (3) a community prevention study (20,000 participants),

conducted with the Centers for Disease Control

and Prevention, to evaluate strategies for the adoption of healthful behaviors including improved

diet, nutritional supplementation, smoking cessation, increased physical activity, and early detection of diseases for women of diverse races, ethnic

groups, and socioeconomic strata. WHI will provide important, scientifically valid information 
13

VOLUME 1

for women, their health care providers, and their

communities. This information will reflect the benefits and risks of preventive approaches and the

means of achieving adoption of these behaviors. 

7. Other fundamental investigations. Studies on the 

following are of particular relevance to women: 

• The genes involved in producing long QT 

syndrome (a risk factor for cardiac arrest) 

and the genes essential for bone formation in 

a mouse animal model have been identified.

The latter is particularly useful in studying 

how to induce new bone development in

patients with osteoporosis or injury.

• Visualization of the brain in action with 

neuroimaging techniques. 

• New categories of drugs to treat depression. 

• The role of abnormal cell death and abnormal

cell reproduction in disease. Telomere length

determines whether or not a cell will divide;

disruptions in telomere function may explain

abnormal cell division or premature aging. 

• Drugs blocking angiogenesis in tumors.

• Factors governing metal transmembrane flux.

These studies will aid treatment of anemia and

elucidate the mechanisms and usefulness of

inflammation and processes of cell repair. 

• Antimalarial drugs aimed at destroying the

three proteins necessary for malarial parasite

development.

8. New and advanced technologies. Laser capture

microdissection, a technique of isolating individual cells from tissue, may lead to the earlier 

diagnosis of malignancies. Other technologies 

relevant to women’s health include: GenBank, 

a central repository for genetic information; the

Cancer Genome Anatomy project, which identifies

molecular fingerprints of genes turned on during

the development of cancers; and new ways to

deliver drugs previously available only by injection.

9. Outreach to special populations. Many outreach 

programs to minority populations are actively

under way, including special programs promoting cardiovascular health for Latinos, and in 

treatment of hypertension and dyslipidemia for

African Americans. Inducements to increase the

interest of women and underrepresented minorities in research careers are under way as part of

NIH’s increasing outreach efforts to minority

groups for careers in science.

The Task Force based the research recommendations provided in these reports on the conclusions

reached by the working groups at the four scientific

symposia. The report recommendations go well beyond the above NIH research topics to incorporate 

the concerns of the Task Force and the working 

groups about other aspects of women’s health. 

Overarching Issues

Despite their wide scope, the scientific reports

herein reveal several overarching themes.

• “Women’s health” is expanding into the larger 

concept of gender-specific medicine. Women’s

health is no longer an isolated phenomenon,

divorced from mainstream medicine and regarded 

as a political or feminist issue. Instead, thoughtful

scientists now see women as important sources 

of new information that will correct essentially

male models of normal function and the pathophysiology of disease.

• The changing needs of women over the course 

of the life span are a common theme in most of 

the reports. Research on women’s health must

include the full biological life cycle of the woman

and the concomitant physical, mental, and emotional changes that occur. This concept was made

particularly clear at ORWH regional scientific

workshops in Santa Fe, which addressed health

issues as they relate to women at all stages of life
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

— during prenatal years, infancy and childhood,

adolescence, reproductive and middle years, periand postmenopausal years, and the elder years.

• Multidisciplinary research is essential. Such

research might be conducted under models like 

that of the program project grant, and involve

teams of investigators with expertise in fields 

ranging from molecular biology to sociology 

and anthropology. It is suggested that the best

results will come from a team in which each 

member is convinced of the intrinsic value of

working together rather than working individually to address an issue or question of interest 

to all. Practically speaking, this will not be easy 

to achieve in academic medicine.

• The importance of social and behavioral science 

to research on women’s health is unquestionable.

Nevertheless, social and behavioral science needs 

to communicate the principles of its discipline 

to the longer-established and more “mainstream”

medical disciplines. It is not now a familiar

resource or partner for conventional research.

• Most clinical studies have been performed in 

men, and virtually all reports urge the collection 

of first-hand information from women to correct

male models of normal function and of the pathophysiology of disease.

Strengths of the Subcommittee Reports

One of the highlights of these reports is the

increased appreciation for the importance of racial, 

cultural, and gender diversity in research populations.

The rich suggestions for future research paths provided

in the immunology and bone and musculoskeletal 

diseases reports are another strength. Other reports,

particularly those addressing cardiovascular diseases

and cancer, are well on their way to realizing new and

particularly innovative programs that will advance not

only women’s health but gender-specific biology. The

pharmacology report provides an excellent review of

the status of our understanding of gender-specific differences in drug metabolism in any given medical field.

This report makes a persuasive case for assessing the

impact of gender on normal human physiology.

The value of the public testimony (an innovative

feature of these symposia) is indisputable. We learned

things that otherwise would not have been heard, and

the lay public and advocacy groups became involved 

in important dialogues with the scientific community. 

This report is the culmination of a 2-year intensive effort on the part of more than 1,500 individuals

nationwide, reflecting a broad spectrum of interests

and expertise in women’s health. Under the guidance of the Task Force members and working group

cochairs, a diverse array of participants evaluated

progress made, identified critical gaps in knowledge,

and formulated cogent recommendations for future

directions in research. We recognize that this massive effort, although not perfect, has laid the key

groundwork from which fruitful partnerships will 

evolve during the next millennium in women’s 

health research.
INTRODUCTION

The issue of how to describe differences in

health status, or in the etiology, progress, 

and treatment of disease between men and

women, is fraught with lexical and conceptual difficulty.

Should differences — for example in rates of heart disease, participation in research, adherence to treatment,

or access to specialty services — be attributed to “sex”

or to “gender?” In the social sciences, the two terms

usually describe conceptually distinct approaches to

understanding difference, “sex” denoting biologically

based differences and “gender” indicating culturally

shaped variations between men and women (or

between notions of masculinity and femininity). 

Unfortunately, the language of difference in the

biomedical literature is often imprecise, conflating the

two terms and treating them as virtual synonyms. This

imprecise use is not only linguistically problematic but

has serious implications for future research, clinical

practice, and treatment, as well as our very understanding of the nature of the health outcomes and status 

differences that we are studying. Without a strong 

conceptual and theoretical understanding of the distinction originally intended by those who clarified 

the difference between sex and gender, confusions 

are replicated. Choosing one term over another may

seem like an innocent matter of semantics; however,

the effects of such language choices and the meanings

that they carry with them have had a significant impact

on the equitable treatment of women in biomedical

research and clinical practice. We must be able to

15

VOLUME 1

THE USE OF “SEX” AND

“GENDER” TO DEFINE

AND CHARACTERIZE

MEANINGFUL DIFFERENCES BETWEEN MEN

AND WOMEN

Jennifer R. Fishman, B.S.

Janis G. Wick, M.A.

Barbara A. Koenig, Ph.D.

Stanford University Center for Biomedical Ethics

define difference to take into account states of wellness and disease that women share with men and

those that they do not. As the research agenda presented in this volume is implemented, a sophisticated

lexicon of difference will be essential to ensure the 

just treatment of women.

THE SEX AND GENDER

DISTINCTION

To understand the tenets of the sex and gender

debate and its effects on current concerns in women’s

health, one must first review the origins of the lexicon

itself. The original distinction between “sex” and “gender” emerged in the mid-20th century. Feminist (and

other) scholars distinguished between those qualities

conventionally attributed to biologically based differences about a person’s “sex,” male or female, and those

qualities that were understood as the result of cultural

and social processes that constitute a person as man 

or woman: one’s “gender.”

This distinction was one part of the challenge to 

the dominant beliefs of the late 19th and early 20th

centuries, which held that difference was biologically

determined and that women’s constitutions were more

biologically driven than those of men. A similar challenge

was made to the notions of biologically determined

racial characteristics attributed to African Americans

and others, which allegedly accounted for differences

in affect, intelligence, and economic status. During the

past 25 years, use of the sex and gender distinction

and lexicon has been fairly widespread throughout
16

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

both the social sciences and the humanities. In fact,

more often than not, “gender” is used in these fields 

to describe differences between men and women to

emphasize the idea that differences cannot merely 

be attributed to biological or physiological processes, 

but rather are almost always influenced by cultural,

social, and historical contexts.

SEX AND GENDER 

IN BIOMEDICAL 

LITERATURE

By contrast, in the biomedical sciences the distinction between “sex” and “gender” has been almost

uniformly ignored. In fact, a quick glance at any database of medical literature reveals that not only are the

terms “sex” and “gender” used synonymously, but that

“gender” is often used instead of “sex” for describing

biological factors, presumably because it is considered

more “politically correct” to do so. This conflation is

common in popular culture as well. However, in light 

of the history of the emergence of “gender” as a conceptual framework, the imprecise and oftentimes careless usage of “gender” in the biomedical literature leads

to misinterpretation and imbues the reported research

results with unintended meanings. At the very least,

the use of the term “gender” implies an acknowledgment and recognition of the sex and gender distinction, and, at most, it implies the understanding that

“sex difference” is the result of complex arrangements

between “biology” (e.g., genetics, hormones, physiology) and “culture” (e.g., hierarchical relationships, historical and geographical location, social interactions).

Yet this implicit meaning often belies the results themselves, for they reveal that no such understanding is

intended. For example, a recent conference entitled

“Gender Differences in Pain” actually focused exclusively on biological differences between men and

women, and therefore might have more correctly 

been titled “Sex Differences in Pain.” Inclusion of 

“gender” in the title implies an understanding of the

social and cultural components of sex differences in

pain perceptions, and, in particular, would include 

discussions of the well established and recognized

observations of the culturally and socially embedded

assumptions that physicians make that women, as

opposed to men, overestimate and inflate their painful

symptoms. However, these topics were not discussed 

at the meeting, which instead focused solely on the

biological determinants of pain perception. The 

conference title, striving for political correctness, 

yielded only mystification.

This confusion is exemplified by recurrent debates

in the “letters to the editor” sections of many medical

journals. In the Journal of the American Medical Association, a letter under the heading “The Eternal Battle of

Sex vs Gender” expressed the author’s distress that, in

the “Instructions for Preparing Structured Abstracts,”

“gender” was used instead of “sex.” However, the complaint was issued not because the author felt that “gender”

implied something in particular about sex differences

that should be considered, but rather that “gender”

should be reserved as a grammatical term referring 

to the masculinity or femininity of nouns (as in most

Romance languages). In other words, nouns can have 

a gender; people only have a sex. The editor’s response 

is equally revealing: while citing various sources for

definitions of gender she concludes that the “evolving

nature of the word gender causes some fuzzy usage . . .

perhaps the time is ripe for a book on One Hundred

and One Things You Wanted to Know About Gender

and Were Not Afraid to Ask.” Although this letter was

published in 1991, the confusion and uncertainty in

medical journal publishing persists. One correspondent

argues that the use of gender in scientific writing as

anything other than the grammatical classification of 

a noun is improper use and “unpardonable.” Echoing

this sentiment, the New England Journal of Medicine

asked an author to “correct” the title of his paper on

gender differences in health insurance, as the editors

felt that the word “gender” referred only to the grammatical case of foreign nouns. The unwillingness of

biomedical journals to consider other uses and meanings of “gender” exacerbates the confusion over the

matter, as the term continues to be used both within 

and outside of biomedical literature.
17

VOLUME 1

NEW DIRECTIONS 

IN THE DEBATE

To further complicate matters, social scientific

research on the sex and gender distinction continues 

to reveal the ways in which this distinction itself does

not reflect the complex relationship between or meanings of both sex and gender. Thus, while biomedical

discourse has not even grappled with the original lexicon of sex and gender, the sex and gender debate in

the social sciences continues to move in new directions, leaving biomedicine further behind. One such

direction is the way in which the designation of “biological sex” itself as a binary concept of male versus

female ignores the realities of both biology and sex.

Social scientists argue that the category biological sex 

is a complex arena in which a variety of genetic, metabolic, and hormonal factors create individuals for whom

a sex is socially assigned. Although one’s sex is most

often determined by one’s genotype (i.e., XX or XY

chromosomes), some scholars argue that the binary

assignment is itself a cultural construct, and perhaps 

it is more appropriate to classify sex on a continuum, 

or at least a categorical system that includes more 

than two categories. Still other scholars study the 

fairly arbitrary assignment of sex that is made for 

individuals for whom no specific “sex” (read: male 

or female) assignment is possible due to physical 

ambiguities. In developed countries, such arbitrary

assignment is often accompanied by genital surgery 

to “fix” any uncertainty in the child’s visible sex. 

These cases beg the question of what is “sex.”

Our understanding of the sexed body, particularly

the female body, and the aspects of it that are deemed

biologically “determined” has actually shifted substantially in the last century. In the late 19th century, biologically determined “femaleness” was thought to be

localized in a particular organ, first the uterus and then

the ovaries. In the early 20th century, the locus of the

biologically determined “essence” of “femaleness” was

viewed as hormonal. In fact, a hormonal conception 

of the body is now one of the dominant ways of thinking about the biological roots of sex differences.

Certainly the interest of biomedicine in the 

hormonal bases for health and disease in women 

is critically important, particularly in light of recent

research on the potential protective benefits of estrogen against heart disease, the popularity of both birth

control pills and hormone replacement therapies, and 

the increase in use of hormones in infertility treatments. However, attention to the hormonal bases 

of health and disease to the exclusion of other contributing factors in women continues to relegate

women’s health to narrow biological definitions.

In addition, we are facing the possibility of yet

another return to biological determinism with the

emerging dominance of genetic models of disease causation within biomedicine. Already in many ways, the

female body is a “genetic” body: her sex is determined

most definitively by her genetic sex or genotype. It is

certainly the case that many are attempting to define

disease states based on genotype. Studies are underway to locate genetic components of breast cancer,

alcoholism, Alzheimer’s disease, and many others. This

trend may have distinctive consequences for women’s

health as the new genomics may serve as a paradigm

for biologically determined “femaleness” as well.

The nature of the relationship between sex and

gender has also been examined by social scientists who

argue that our notions of the ways that gender “maps

onto” sex may be simplistic and may neglect the diversity of experiences of both men and women. Although

there is the desire to separate that which is biologically

determined about sex differences and that which is

social, cultural, and environmental, scholars have since

argued that neither sex nor gender — nor the relationship between sex and gender — can be understood so

simplistically. However to lump everything into either

the sex or gender category, depending on political or

disciplinary persuasion, is equally problematic, for

one’s linguistic decision implies assumptions about the

nature of difference. As a result, feminist scholars have

been attempting to move past the sex and gender distinction without neglecting or dismissing the pull of

biological determinism whenever discussing sex or 

the complex real life experiences of men and women.
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A GENDA FOR R ESEARCH ON W OMEN ’ S H EALTH FOR THE 2 1 S T C ENTURY

EQUITABLE AND JUST

TREATMENT FOR WOMEN

The lack of an appropriate lexicon of sex difference in biomedicine has had a serious impact on the

just and equitable treatment of women in biomedical

research and clinical medicine. The ambiguity and 

confusion about appropriate language speaks of a 

larger ethical problem of how it is that sex difference

has been conceived, studied, and addressed in biomedicine. Our understanding of the nature, importance, 

and implications of sex difference is growing, as should

our understanding of the complexities and dilemmas 

of researching and reporting such differences. It was

not long ago that women were routinely excluded 

from large-scale clinical trials. For instance, most trials

for the prevention of heart disease studied middle-aged

males and excluded women because of a complex set

of assumptions, including the perception that women’s

hearts were the same as men’s. In this case an assumption of sameness led to unethical and neglectful treatment of women. Yet, one of the reasons women were

not included in these trials is because of the perception

that women’s bodies (hormonally and reproductively)

behaved very differently than men’s and that these 

factors would complicate the collection of safe and 

reliable data. Therefore, women were enough like men 

to warrant exclusion from clinical studies, yet they

were too different to be included as part of the same

study. This confusing and paradoxical attitude toward

sex difference in clinical trials demonstrates the complexities and problems attending to sex difference. 

The human subject guidelines have changed to require

the inclusion of women in clinical trials, yet the question remains as to how similarities and differences

between men and women will be explored, studied, 

and compared.

In some cases of biomedical research and clinical

treatment, sex difference is not explicitly attended to,

yet its implications lie just below the surface. An example of this phenomenon is the treatment for women

with depression. Although we have sufficiently documented the higher proportion of women than men 

who are medically treated for depression, we have not

turned our attention to the implications of this difference. It is here that the sex and gender debate may 

well be able to provide a backdrop for studying this

observed difference. In other words, does noting this

difference between men and women unknowingly

imply that the difference can be attributed to biological factors? Are women at higher risk for depression

simply by virtue of being female? We can hypothesize

many explanatory models for this observation, ranging

from biological and hormonal factors that predispose

women to depression to a “cultural” model that would

explore the mental health consequences of sociocultural

stratification, including women’s greater tendencies to

seek medical care in concert with physicians’ tendencies to pathologize women’s mental health problems.

The model we hypothesize depends on our perceptions

and conceptualization of the nature of sex difference

itself; leaving that conceptual base unexamined is 

dangerous for women’s health and women’s health

research. It is also of potential harm to men. Pfeffer

(1985) argues that men’s reproductive health problems have conventionally been treated similarly to

women’s health problems, that is, pathologized.

Accompanying the conceptual difficulties associated with the lack of an appropriate lexicon of difference is an inability to explore underlying causes of

“women’s” diseases. The effects of this inability on

treatment are enormous. One example is the way 

in which tranquilizers have been prescribed to large

numbers of women, based on the assumption that 

such drugs are “safe” and “non-addictive,” and that

women must be “naturally” more nervous and 

anxious than men. The treatments offered women 

in these cases, most often prescription drugs, have 

been unnecessarily limited due to a lack of conceptual understanding of the underlying causes for 

the differences in women’s experiences.
19

VOLUME 1

A further ethical concern stems from the recurrent

debates about “nature” versus “nurture” that have become

an inherent part of the emergence of the biotechnologies

of genetic testing. With the Human Genome Project

more than halfway complete, biomedical researchers

and clinicians face questions daily about what exactly 

is biologically determined and what can be attributed

to “environment,” or perhaps the even harder question

of how do genes (or one’s biological make-up) interact

with one’s environment? Sex differences become part of

this complex set of questions: in the same way that we

must look at the complex interplay between “biology”

and “culture” to understand disease causation, prognosis, and treatment options, we must also look at the

differences between men and women. Ethically, this is 

a difficult task. In the case of the new biotechnologies

that allow for genetic testing for susceptibility to disease, the ethical implications of developing, offering, 

or performing such tests are enormous. If we offer

someone a genetic test for a disease that cannot be prevented or cured, are we offering patients meaningful

choices? This is equally true for questions about the

nature of sex difference. To assume that the differences

in health status or outcomes between men and women 

is biological leaves us a restricted set of choices for

research and treatment. If we do not explore the complex relationship between “nature” and “nurture,” how

can we conduct appropriate research into health and

disease in women and treat them fairly?

The use of an imprecise lexicon for describing 

differences between men and women in biomedical

research has consequences for the conduct of science 

as well as for the clinical treatment of women. In each

of the above examples, and in numerous others, the

use of categories of “men” and “women” for describing

difference assumes that the differences between the 

two categories are greater than differences within the 

two groups. By relying on sex category differences as 

the primary marker of difference other potentially

important factors may be ignored, for example the

complex interaction of race, sex, and social class within

our health care system. This case has been effectively

made for the social category of race, where both the

ethics and the science of research based on differences

between racial categories has been questioned. Within

biomedical research that studies racial difference, there 

is often the implicit assumption that the differences

between racial groups are biologically based or genetically determined. Yet many have problematized this

assumption, pointing out the ways in which there are

often larger differences within categories than between

them. Moreover, documenting differences based on

supposedly categorical differences between races within

biomedicine not only assumes that such differences are

somehow inherent to those within that racial category,

but also has the potential to stigmatize and blame those

considered within that category for falling ill. This

affects clinical visits and treatment options for such

individuals. Assumptions about categorical differences

between the sexes is no different, and should be held

equally suspect. Indeed, both “race” and “sex” characterizations have often been used not for delineating

important differences in terms of treatment but for

underlying political and cultural reasons that have

proved highly detrimental to both women and racially

stigmatized groups. Developing a precise lexicon of 

sex difference would be a primary step away from 

such deleterious distinctions, for it demands that we

focus on the ways in which we measure and report 

differences between men and women, and most 

importantly allows us to specify what these differences mean for biomedical research and ultimately 

for patients in clinical settings.

The authors wish to thank Adele E. Clarke and 

Nancy Fugate Woods for helpful comments on earlier 

drafts of this manuscript.

Reports of the Working groups:

Scientific Chapter — 

Summary of Recommendations

23

VOLUME 1

Women’s use of alcohol has resulted in 

a major public health problem; women

represent one-third of the estimated 14

million alcohol-abusing or alcohol-dependent people 

in the United States. In 1995, the National Household

Survey on Drug Abuse reported that, of an estimated

12.8 million Americans ages 12 and older who used 

an illicit drug during the past 30 days, 4.3 million were

women of childbearing years. Although fewer women

than men use drugs, the potential consequences of

drug abuse are often different for women. Tobacco 

use is responsible for more than 500,000 deaths in 

the United States each year; nearly a third of these 

are women. Although tobacco smoking has declined

among men by 84 percent during the past three

decades, smoking rates among women declined 

only 21 percent during this same period.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the alcohol and other drug field:

• Gender as a Research Variable. Researchers now pay

significant attention to gender differences in the

analysis and reporting of epidemiologic data, for

example in surveys such as the national probability

sample survey focusing on alcohol and other 

drug use among women. Studies are beginning 

to examine the role of the menstrual cycle in 

patterns of alcohol and other drug use.

• Study Design Issues. Improved study designs 

recognize the importance of effective dosage 

when prescribing medications for female 

patients as well as issues of access, entry, 

and retention of women in treatment. 

• Domestic Settings. The family as the unit of 

analysis is a major new focus, in particular 

the interaction of prenatal alcohol and drug 

exposure and postnatal environment and status 

of the mother and family. Violence and sexual

abuse are now recognized as factors in alcohol 

and drug use among female victims, leading to

recognition that abused women need comprehensive services beyond drug and alcohol treatment.

• Studies To Examine the Genetic Basis of Alcoholism 

in Women. Although not conclusive, these studies

do permit tentative conclusions about the role of

inheritance in alcoholism among women, which

can be applied to future research.

Alcohol, Tobacco, 

and Other Drug Use, 

Disorders, and 

Consequences
24

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

RESEARCH 

RECOMMENDATIONS

• Drug Use Patterns and Treatment Models. Studies

should be undertaken that describe the role of 

gender in sensitivity to pain medication, the biochemical effects of drug use, self-medication, and

use of psychotropic prescription drugs, including

health benefits, in the development of treatment

strategies for alcohol and drug use.

• Developmental Effects. An examination of the effects

of maternal alcohol and drug use on children’s use

of alcohol and drugs should be undertaken.

• Predisposition to Mood, Eating, and Anxiety Disorders.

Further research should be conducted with a view to

better understanding the role of mood, eating, and

anxiety disorders in alcohol and drug use, as well

as those psychological, social, and biological factors

that predispose young women to these disorders.

• Effects of Victimization and Violence. Conduct

research on sexual abuse during childhood, and 

the interaction between other sexual or violent 

victimization of women and their use of alcohol 

and drugs.

• Biological and Physiological Gender Differences. 

Studies should be conducted that detail gender 

differences in health consequences that occur

across a spectrum of consumption and use levels.

• Media and Advertising. The influence of the media

and advertising on a woman’s use of alcohol and

drugs including tobacco should be further examined.

• Gender-based Treatment. Studies that examine 

the role of ethnic and gender variation in how 

alcohol and drug users perceive the need for 

treatment should be encouraged, from childhood through adulthood.

• Prevention Strategies. Develop counseling techniques

for adolescent and adult females who may have a

genetic risk of alcohol and drug use and/or abuse.

Develop prevention strategies to account for the

role of childhood violence and sexual abuse in 

adolescent and adult females’ use of alcohol and

drugs; related studies to appropriate interventions. 

• Intervention Strategies. Emphasize early intervention

with girls and adolescents in prevention studies

designed to reduce individual and social environmental risk factors. Base interventions on etiology

and pathway findings for females versus males.

“In view of the trends toward an aging American

population, and the relative longevity of women in

comparison to men, special attention should be paid to

the impact of alcoholism and drug abuse on the health

of perimenopausal and postmenopausal women.”

Nancy K. Mello, Ph.D.

Harvard Medical School
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VOLUME 1

Behavioral and 

Social Sciences

The World Health Organization defines 

health as “a state of complete physical, 

mental, and social well being and not 

merely the absence of disease or infirmity.” This 

definition not only expresses the interrelatedness 

of mind, body, and social context but also stresses 

the positive meanings of health. The NIH Office 

of Behavioral and Social Sciences Research (OBSSR)

has identified five crosscutting themes in behavioral

and social sciences research: an emphasis on theorydriven research; the search for general principles of

behavioral and social functioning; a developmental, 

life span perspective; an emphasis on individual variation across sociodemographic categories such as 

gender, age, and sociocultural status; and a focus on 

both the social and biological contexts of behavior.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the behavior and social science fields:

• Research Design. As a result of increased awareness

and knowledge of gender and behavioral and social

factors and of explicit law and regulations, survey

samples and study populations more routinely

include women and are more likely to reflect at

least some of the geographic, racial, and ethnic

diversity of the general population. A large body 

of methodological research has illuminated the

influence of context on the study or interview 

situation and the need to match interviewers and

respondents on certain characteristics (e.g., language) to elicit the most valid and reliable data.

• Behavioral Methodologies. Health researchers on

health topics are increasingly using the methods

developed by behavioral and social scientists, 

especially focus groups, to gather information 

on attitudes and behaviors. There is a growing

recognition among policymakers and researchers 

of the need to involve community members in

defining key research questions and collecting 

data on those communities, and of the merits 

of other community-based and participatory 

forms of research.

• Violence and Women’s Health. Violence has recently

been recognized as an important issue in the study

of women’s health. Great progress has been made

in a relatively short time in understanding the

extent to which women experience violence in

their lives, the consequences for women, and 

the development of effective treatments.

• Heart Disease. Heart disease has long been the

major cause of death among women in the United

States, but it was not recognized as a major health

problem in women until recently. Since 1991, 

a number of studies have been and are being 
26

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

conducted to fill in gaps in knowledge about 

heart disease in women (e.g., the Nurses Study,

Postmenopausal Estrogen/Progesterone Intervention, the Women’s Health Initiative, Study of

Women’s Health Across the Nation). These studies

examine behavioral factors (e.g., exercise, diet,

stress, social support) and their relationships 

to cardiovascular health outcomes.

• Genetic Screening and Breast Cancer. The rapidly

advancing world of genetic research is leading to

the availability of genetic screening for an increasing number of diseases. Important research has

been conducted examining women’s perceived risk 

of breast cancer, evaluating counseling programs

and identifying women who may benefit most 

from counseling.

RESEARCH 

RECOMMENDATIONS

• Basic behavioral and social science should study

decisionmaking processes regarding adoption 

and maintenance of health behaviors, investigate

gender roles, and study culture and social context.

• Collaborative, multidisciplinary research that 

incorporates behavioral and social science into 

biomedical and clinical studies should explore 

preventive factors, study treatment, and investigate the care and caregiving experience.

• Methodological research should be used to determine innovative measures that reflect women’s

lives, devise innovative data gathering strategies

including qualitative and community-based

approaches, and explore effective methods of

recruiting and retaining women in studies.

• Funding and training policies and practices 

should be altered to: 

– Sponsor a workshop on multiple factors 

affecting women’s health decisionmaking.

– Develop mechanisms to ensure funding 

of research on relevant behavioral and 

social components.

– Ensure that study sections have adequate 

expertise to review behavioral and social 

science components of women’s health 

proposals.

– Fund training grants for behavioral and 

social scientists working in medical areas.

– Provide boilerplate language for appropriate

Request for Applications in every NIH institute or center.

• The institutions that educate and train health 

professionals should integrate behavioral and 

social science relevant to women into health 

professional curricula, develop a process for 

integrating new advances, and devise ways to 

test students on their knowledge in this area.

• Special initiatives should be undertaken to 

conduct clinical trials related to behavioral 

interventions, explore physical activity, and 

study violence.
Bone and 

Musculoskeletal 

Disorders

Bone and musculoskeletal disorders are responsible for high disability and high cost to society and thus are of significant public health

importance. Arthritis and orthopaedic conditions,

including fractures due to osteoporosis, are among the

leading causes of disability and activity limitation in 

the United States. Many of these conditions are more

prevalent in women than men and have gender-specific

manifestations, etiology, impact, and possibly outcomes

of treatment. The initial focus and efforts in women’s

health have been appropriately on the diseases with

acute mortality or female specificity; now it is timely 

to focus on the diseases and conditions that reduce 

the quality of women’s lives and limit their activities 

as well as contribute to large health care expenditures.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the bone and musculoskeletal fields:

• Arthritis and Musculoskeletal Disability. Basic science

related to the pathophysiology of arthritis has been

advanced in the last several years, and there has

been enormous progress in understanding the 

role of self-management in living with arthritis.

Specific advances in our knowledge of arthritis 

and its treatment and management include:

– Better understanding of cartilage cell physiology, matrix factors, and enzymes cofactors.

– Improvements in joint replacement surgery.

– Progress toward the goal to achieve a better

quality of life and acceptance of impairment 

or disability in a wider range of the arthritic

population.

– Exercise studies indicating beneficial outcomes

for arthritis patients, including pain relief.

– Reliable and validated tools for assessing 

functional capacity, activity limitations, 

psychological status, and quality of life.

• Osteoporosis and Fractures. Significant advances have

been made in understanding the biology of bone

remodeling and functions of various cells in the

skeleton, and new treatment options and sophisticated assessment technologies are now available.

Recent progress assists in understanding how 

calcium and physical activity affect bone health.

• Orthopaedics and Physical Activity. Total joint replacements have provided enormous relief from pain

and disability for individuals with end-stage joint

disease. Improved fracture fixation techniques and

surgical techniques for soft tissue injuries have

returned people to work and sport activity quickly.

Carpal tunnel syndrome has been recognized, and

some of the factors that may predispose to this

condition have been uncovered.

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RESEARCH 

RECOMMENDATIONS

Arthritis

• Investigate the greater prevalence and triggers 

of arthritis in women. 

• Explore the biological and mechanical factors 

that influence the progression of arthritis.

• Examine biological repair processes and bioengineering approaches to tissue regeneration.

Osteoporosis

• Understand the factors that contribute to the development of peak bone mass (e.g., diet, exercise,

puberty, pregnancy, smoking, environment).

• Focus on clinical trials to develop treatment and

prevention studies that will not be conducted by

the private sector — combined drug therapies, 

exercise, and nutrition studies.

• Further refine biological markers and other 

assessment technology.

• Focus on maintenance of bone mass throughout life — identify genetic and lifestyle factors

associated with bone loss.

• Explore quality-of-life issues in women with 

osteoporotic fractures.

• Explore the role of physical activity in preserving muscular strength, balance, and coordination 

as a means of preventing falls in the elderly.

• Develop specific exercise regimens that affect 

the bone at the major sites of fracture (i.e., 

hip, spine, and wrist).

Orthopaedics

• Investigate the role of women’s footwear 

in pain, disability, and falls.

• Determine the prevalence and etiology 

of stress fractures and other overuse 

syndromes — repetitive stress injury.

• Investigate the molecular signals that 

control repair and growth in cells of 

the musculoskeletal system.

0

10

20

30

40

50

60

■ Have Arthritis, but not limited by it

■ Limited by Arthritis

Source: National Center for Health Statistics, Health, 

United States, 1995.

45-64 Years of Age

Percent

65-74 Years of Age 75 Years of Age & Over

WOMEN MEN WOMEN MEN WOMEN MEN

Proportion of persons with arthritis 

and proportion with limitations of 

activities due to arthritis by age and 

sex: United States, 1993-94.
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VOLUME 1

• Develop synthetic replacements for muscle, 

soft tissue, and bone damaged beyond repair.

• Explore knowledge of the interaction of the

immune system and its role in transplantation 

of bone and ligaments.

• Study the relative influences of osseous anatomy,

ligamentous laxity, and sex hormones on musculoskeletal disorders.

• Explore gender variation in treatment outcomes.

Physical Activity and Sports Medicine

• Improve measures of energy expenditure and its

benefits to the musculoskeletal system — whether

leisure time exercise plays a different role from

household or occupational activities.

• Determine the type, intensity, duration, and 

frequency of physical activity that is important 

for musculoskeletal health.

• Investigate gender differences in sports injuries 

— endocrine, structural, and training factors 

that lead to injury.

• Explore the “female athlete triad,” including 

contributing factors such as nutrition, energy

expenditure, and stress.

• Understand the role of physical activity in 

the development of bone, tendon, ligament, 

and muscle.

Data Needs and Information Dissemination

• Provide information from national data 

surveys and large cohorts on prevalence 

and treatment outcomes.

• Improve surveillance of injury patterns in 

physically active women of all ages.

• Improve, develop, and validate instruments 

that measure physical activity and relate it 

to health outcomes — improved performance measures.

• Develop effective information dissemination

processes.

• Develop methods for tracking and improving 

compliance with effective therapies.

“. . . women’s health issues are long on numbers,

large on disability and suffering, and enormous in 

cost. To reduce suffering and disability, we need to 

prevent these disorders when we can, diagnose them

early to minimize their impact, and provide interventions to maximize functioning in patients who 

have them. We want our daughters and their 

daughters to travel a different road than we have.”

Laura Tosi, M.D.

American Academy of 

Orthopaedic Surgeons

Cancer

Cancer remains a major public health problem, causing untold anxiety and suffering for

patients and their families and generating a

substantial part of the nation’s health care expenditures.

In 1997, an estimated 596,000 women were diagnosed

with cancer, and 265,900 women died of the disease.

Cancer is the leading cause of death for 35- to 74-yearold women. Lung cancer continues to be the leading

cause of cancer deaths for women, followed by breast

and colorectal cancers. 

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the cancer field:

• U.S. mortality rates for breast and colorectal 

cancers have decreased among Caucasian 

women.

• Scientists have identified genes associated 

with cancer and signaling pathways responsible for loss of cellular control mechanisms, 

greatly improving the understanding of 

carcinogenesis.

• New associations between infections and 

cancers have been found, and a mechanism 

for viral carcinogenesis has been identified.

• The idea that cancer may be a preventable 

disease is closer to reality. Clinical trials have 

evaluated retinoids to prevent various cancers 

and tamoxifen to prevent breast cancer.

• Many researchers now examine gender, socioeconomic, and racial and ethnic differences 

when studying cancer incidence, mortality, 

and prevention.

RESEARCH 

RECOMMENDATIONS

• Identify and develop effective diagnostic 

screens for all cancers.

• Develop chemoprevention strategies and 

vaccines against cancer.

• Develop improved treatments, reliable biomarkers, and imaging technologies for the 

early detection of lung cancer.

• Give high priority to smoking prevention 

and intervention programs.

• Evaluate the cumulative effects of environmental, exogenous, and endogenous estrogens

(including DES, HRT, and oral contraceptives) 

on cancer risk, and develop safer medications, 

if needed.

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• Study the social, ethical, legal, and economic 

effects of new commercially available genetic 

tests, and develop appropriate counseling 

models linked to genetic testing. 

• Design, evaluate, and implement culturally 

competent interventions to overcome barriers 

to women’s participation in cancer prevention,

detection, treatment, and outcomes research.

Include older women, minorities, and rural

women, traditionally underrepresented, as 

a high priority.

• Continue basic research to define cancer 

mechanisms, identify high risk individuals, 

and develop new strategies for treatment.

• Develop prevention and screening strategies 

that will increase the survival of persons at risk.

• Teach health care providers communication skills

that encourage health-promoting behavior in their

patients and the public. 

• Address quality of life issues in cancer survivors.

Percentage of High-School Students Who Were Smokers in the Previous Month, 1990-19949

AMERICAN INDIANS & ALASKA NATIVES ASIAN AMERICANS & PACIFIC ISLANDERS BLACKS HISPANICS WHITES

GIRLS 39.4 13.8 8.6 19.2 33.1

BOYS 41.4 20.6 11.6 28.5 33.4

“The tragic and commanding fact about 

ovarian cancer is that more than 50 percent of the 

women who have it die within 5 years of diagnosis.”

Ann Kolker

Ovarian Cancer 

National Alliance: 

Ovar’coming Together
Cardiovascular 

Diseases

Heart disease has been the number one killer

of women for nearly a century. Cardiovascular disease (CVD) accounts for about 57

percent of all deaths among American women. Of the

more than 960,500 deaths from heart attack each year,

more than 52 percent occur in women. Cardiovascular

disease kills almost twice as many American women as

all cancers combined and more than 11 times as many

women as does breast cancer. Older women who have

suffered heart attacks are twice as likely as men to die

from them within a few weeks. About 44 percent of

women who have heart attacks die within 1 year,

whereas only about 27 percent of men die within 1

year. Among women who die suddenly of coronary

heart disease, 64 percent have no previous symptoms,

compared with 48 percent of men. The heart attack

death rate for African-American women between the

ages of 35 and 74 is about twice that of Caucasian

women and three times that of women of other races.

Stroke, America’s number three killer, killed about

158,000 people in 1995, and of these, 61 percent 

were women. Stroke kills twice as many women 

as does breast cancer.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the cardiovascular field:

• Basic and applied CVD research funding for

women’s health has increased.

• Types of research (health services, cost effectiveness, population-based, community) pertaining 

to women’s health have increased.

• Participation of women in clinical studies, 

especially diverse groups of women, has 

continued to increase.

• New cardiovascular treatment regimens in 

women’s health have been developed.

• The CVD death rate in women is 37 percent 

lower than it was in 1900.

RESEARCH 

RECOMMENDATIONS

Developmental Biology of the Vascular System and

Role of Fetal Environment in Programming Lifelong 

Cardiovascular Function

• Study the developmental biology of the vascular

system and role of fetal environment in programming lifelong cardiovascular function.

• Evaluate the interaction of nutrition and cardiovascular development, using animal models.

• Study the maturation of central nervous system

functions and how they regulate the functioning 

of the cardiovascular system.

• Explore the interrelationship of renal development and cardiac function.

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Molecular and Physiologic Mechanisms of Hormone

Action in the Cardiovascular System

• Characterize estrogen receptors in vascular 

tissue and vascular cells, including vascular

endothelial cells and smooth muscle cells.

• Identify the relative amounts of mRNA and 

protein for estrogen receptor alpha and estrogen receptor beta in different vascular cells and

beds, in women versus men, in premenopausal 

versus postmenopausal women, and in the presence or absence of hormone replacement therapy.

• Study molecular mechanisms of estrogen action in

vascular cells, with an emphasis on novel pathways

in vascular cells, including ligand-independent activation of vascular estrogen receptors and vascular

cell co-activator and co-repressor molecules.

• Examine molecular mechanisms of estrogen’s

nongenomic vasodilatory effect on the vasculature

and estrogen’s longer-term effects to inhibit atherosclerosis and the response to vascular injury.

• Identify and study vascular genes regulated by

estrogen, including identification of novel vascular gene targets of estrogen and study of vascular

estrogen response elements in these genes.

• Characterize and study other steroid (progesterone and androgen) hormone receptors in 

the vasculature of women and men and their 

gene targets.

Cardiovascular Implications of Diabetes and Obesity

• Develop and evaluate strategies to improve the 

outcome of women with diabetes.

• Study the interactions between estrogen and diabetes on blood vessels and the heart, and the potential

role of ERT in protecting postmenopausal diabetic

women from developing cardiovascular disease.

• Examine the impact of aggressive modification 

of other risk factors on cardiovascular outcomes 

in diabetics.

• Study prenatal precursors to obesity.

• Study genetic, molecular, and hormonal factors 

in obesity and why they cause obesity to be a

greater problem in women than in men.

• Examine environmental factors in the expression 

of a predisposition to obesity, and the development of approaches to alter the environment 

to avoid or address obesity.

• Study the roles that various stages of life play 

in placing women at increased risk for obesity 

and how to address these risks.

“As obesity is becoming more prevalent, 

particularly among women, and affects a number 

of risk factors as well as risk for coronary heart 

disease itself, further research into its causes and

treatment are needed.”

Marian C. Limacher, M.D.

American College 

of Cardiology
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VOLUME 1

• Investigate modifiable societal 

and community factors that 

result in increased obesity and

ways in which to change these 

factors to reduce the prevalence 

of obesity.

• Study effective therapeutic modalities to prevent or treat obesity,

especially physical activity.

Prevention, Detection, and 

Management of Cardiovascular 

Disease in High-risk Populations

• Examine the dimensions of cardiovascular disease 

in high-risk populations, including women who

are octogenarians and older, racial and ethnic

minorities, and disabled women.

• Study the impact of patient and health care professional behaviors on cardiovascular disease 

development and prevention in women.

• Evaluate why the general public, patients, 

and health care professionals do not act on 

well-known prevention information despite 

its widespread availability.

• Determine exercise, nutrition, smoking, and 

other lifestyle behaviors related to the development of cardiovascular disease among 

women patients.

• Develop methods to increase the effectiveness 

of cardiovascular disease prevention interventions and education efforts.

• Evaluate the education, prevention, diagnostic,

treatment, and management procedures followed

by health care professionals with respect to cardiovascular disease and how these differ by gender,

age, and race and ethnicity of patients.

Women’s Perceived and Real Health Risks

PERCEPTION PERCENT CAUSE OF DEATH PERCENT

Breast cancer 46 Heart disease 34

Unspecified cancer 16 Other cancer 12

Heart disease 4 Stroke 8

AIDS 4 Lung cancer 5

Uterine/Ovarian cancer 3 Breast cancer 4

Source: Vital Statistics of the U.S., National Center for Health Statistics

Digestive Diseases

Recent research has yielded important information on gender differences in digestive 

diseases. Gender-based differences have been

identified in several areas, including irritable bowel

syndrome and functional bowel disorders, colorectal

cancer detection, gallstone disease, liver disease, and

metabolic bone disease. The discovery of genetic bases

in certain colon cancers, gallstone disease, and liver

diseases is another advance of vital importance.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the digestive diseases field:

• The functions of specific brain peptides, nitric

oxide, carbon monoxide, and other factors in 

gastrointestinal motility that affect irritable bowel

syndrome (IBS) and functional bowel disorders

(FBD), and in relating sensory dysfunction, pelvic

floor dysfunction, motor dysfunction, and psychosocial factors, including physical and sexual

abuse, to these disorders.

• Identification of four distinct genes that, when

inherited in altered form, cause increased susceptibility to colorectal cancer at unusually early 

ages, plus identification of a gene associated 

with familial adenopolyposis.

• Screening for colorectal cancers in that studies 

have shown that screening with fecal occult 

blood testing or sigmoidoscopy is associated 

with decreased mortality from these cancers.

• Identification in an animal model of genes associated with gallstone disease, the evolution of

laparoscopic cholecystectomy as the most common technique for gallbladder removal, and the

determination that certain drug therapies may 

prevent the formation of gallstones in patients

experiencing rapid weight loss.

• A greater understanding of the mechanisms of 

nonsteroidal anti-inflammatory (NSAID)-induced

damage to the gastrointestinal tract, along with 

a greater understanding of the mechanism for 

cytoprotection of the gastric mucosa.

RESEARCH 

RECOMMENDATIONS

Irritable Bowel Syndrome and Functional 

Bowel Disorders

• Determine why these conditions affect so many

more women than men.

• Further elucidate the mechanisms of gut motility.

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• Clarify smooth muscle physiology.

• Identify and characterize the influences on 

gut motility and smooth muscle physiology 

of various brain peptides and neurotransmitters 

such as carbon monoxide and nitric oxide.

• Develop a clearer understanding of the functioning of the enteric nervous system.

• Explain how heightened sensitivity to pain 

and other sensory dysfunctions are involved 

in IBS and FBD.

• Examine the relationship between pelvic floor 

dysfunction and IBS and FBD.

• Study the effects of the menstrual cycle on 

IBS and FBD.

• Elucidate the role of environmental and other 

stressors, developmental influences, and biopsychosocial factors in these conditions.

• Validate diagnostic criteria.

• Further identify and target specific pharmacologic and other therapeutic interventions (such 

as stress reduction techniques), and alternative

health interventions (such as acupuncture and 

family therapies) for IBS and FBD.

Colorectal Cancer

• Determine how interventions such as postmenopausal estrogen therapy and low-fat diets 

affect the risk of colorectal cancer in women.

• Develop more cost-effective methods for early

detection of colorectal cancer.

• Devise methods to educate women and health 

care providers about the importance of screening for colorectal cancer.

• Explore genetic identification of high-risk groups.

0

5

10

15

20

25

30

■ FEMALES

■ MALES

Source: Third National Health and

Nutrition Examination Survey

Age-adjusted Prevalence 

of Gall Bladder Disease

Among Adults According 

to Ethnicity and Sex

U.S. Whites Mexican Americans Blacks
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VOLUME 1

• Explore the relationship between hereditary colon

cancer and ovarian and endometrial cancers.

Gallstone Disease

• Investigate gender differences in cholesterol 

metabolism and excretion in bile.

• Explore the effects of gender on interactions

between gallbladder physiology and gut motility.

• Identify how sex hormones influence the expression of recently identified genetic factors.

• Elucidate the physiological functions of the 

gallbladder and factors that influence the 

gallbladder functions of motility, secretion, 

and absorption.

• Improve diagnosis and methods to predict 

patients who will develop complications of 

gallstone disease.

• Investigate the etiology and natural history 

of gallstones formed during high-risk periods 

such as pregnancy and weight loss.

• Explore the reasons for ethnic variations in gallstone disease (such as the high incidence among

American Indians and Mexican Americans).

• Investigate potential preventive measures.

Liver Disease

• Better understand non-alcoholic steatohepatitis,

including (a) why women are more susceptible; 

(b) what the natural history is, including who

develops cirrhosis; (c) what the molecular 

mechanisms and genetic and environmental 

susceptibility factors are; and (d) treatment 

and prevention strategies.

• Explore pathogenesis, immunology, and therapeutic approaches to primary biliary cirrhosis (PBC).

• Explore influences of sex hormones on elements 

of the immune system related to autoimmune 

liver diseases.

• Better understand hepatic cell growth and 

investigate the influence of sex hormones 

on the proliferation of liver cells and the 

growth of tumors.

• Identify safe and effective therapies for 

PBC and autoimmune hepatitis.

NSAIDs and Peptic Ulcer Disease

• Develop tolerated medications for preventing 

gastrointestinal ulceration and bleeding experienced as side effects by those who rely heavily 

on NSAIDs to control pain from arthritis and 

other disorders. Involve women in sufficient 

numbers so as to yield meaningful information 

on prevention strategies for women.

“Irritable bowel syndrome predominantly 

affects women. Approximately 75 percent of 

individuals with IBS in the community are female,

with the incidence being reported as high as 90 

percent in some medical centers. This is a major 

women’s health issue.”

Nancy Norton

International Foundation 

for Functional 

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

Metabolic Bone Disease

• Better understand the mechanisms of calcium

absorption through the intestines in health and 

disease and how they change with age.

• Clarify the relationship between inflammatory

bowel disease and osteoporosis and osteopenia in

order to develop improved treatment modalities.

• Clarify the relationship between primary biliary 

cirrhosis and osteoporosis and osteopenia in 

order to develop improved treatment modalities.

• Develop better methods for evaluating and 

treating bone loss that accompanies chronic 

liver disease.

• Determine the extent to which bone loss in 

chronic liver diseases may be restored after 

liver transplantation.

Digestive Diseases During Pregnancy

• Investigate the influence of hormones on 

various digestive disorders that may be 

present during pregnancy.

• Investigate the etiology and natural history 

of gallstones formed during pregnancy.

• Determine the safety profiles in pregnancy 

of procedures used to diagnose and treat 

gastrointestinal conditions.

• Determine the safety profiles in pregnancy 

of drugs used to treat chronic gastrointestinal conditions.

• Investigate whether the absorption and 

metabolism of drugs used to treat chronic 

gastrointestinal conditions changes 

during pregnancy.

• Further clarify the causes of acute fatty 

liver of pregnancy and develop improved 

treatment and prevention strategies.
Immunity and 

Autoimmune Diseases

Women’s health depends significantly on

the appropriate function of the immune

system. Asthma and allergic diseases are

important sources of morbidity in women. Autoimmune diseases, in which the immune response is

directed at the body’s own tissues, disproportionately

afflict women. In addition, the immune response is

important in protection against many infections, such 

as sexually transmitted diseases, and their sequelae.

Evidence exists that there may be differences in the

function of men’s and women’s immune systems,

including the fact that women are able to tolerate 

without rejection a fetus during pregnancy.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the immunity and autoimmune field:

• Degradation of antigens intracellularly and their

presentation to the immune system.

• Identification of subtypes of T cells and their 

role in immune activation and regulation.

• Development of B cells and their role in 

cellular immune responses.

• Identification of many soluble molecules including cytokines and chemokines, and their role 

in the immune response.

• Trafficking of immune cells to various areas 

of the body.

• Inter- and intracellular signaling cascades.

• The pathways leading to cell death.

• Interactions of the various components 

of the immune system. 

• The critical role played by the immune system in many diseases that were not previously

thought to be immunologically mediated, 

increasing the need to understand immune 

function throughout the life span.

• Development of new research tools, for 

example, polymerase chain reaction (PCR). 

• Analysis of large numbers of samples facilitated 

by synthetic and recombinant peptide libraries.

• Screening of defined populations for genetic 

differences, made possible with the development of large patient and family repositories 

as well as newer genetic screening and 

sequencing methods.

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RESEARCH 

RECOMMENDATIONS

• Address the gaps in knowledge and exploit 

the opportunities defined above.

• Design information systems that allow easier 

access to archival material on clinical and 

genetic studies.

• Increase multidisciplinary research.

• Increase sharing of resources among researchers 

(this includes sharing of clinical samples, DNA

banks, serum banks, animals, and reagents).

• Communicate more effectively between the lay

public and the scientific community, making 

information readily accessible to researchers, 

health care providers, and consumers.

• Stratify future and existing data from basic and 

clinical studies for sex and age of subjects.

• Identify resistance and susceptibility genes for

multigenic diseases such as rheumatoid arthritis,

systemic lupus erythematosus, multiple sclerosis,

scleroderma, Sjögren’s syndrome, Type I Diabetes,

and asthma.

• Identify the effects on immune function of 

environmental influences such as diet, stress, 

allergen exposure, and exogenous estrogens.

• Study the comparative effects of sex and age 

on normal and abnormal immune function in 

animals and humans; determine the role of stages 

of the menstrual cycle on immune function.

• Determine the effects of sex steroid hormones 

(estrogens and androgens), other hormones, 

and hormone fluctuations on different aspects 

of the immune response.

• Identify the immunologic environment in the 

target organ in various autoimmune diseases — 

the brain in multiple sclerosis, the joint in 

rheumatoid arthritis, the beta cells in diabetes, 

the kidney and vasculature in systemic lupus 

erythematosus, the lung in asthma, and the 

skin in scleroderma.

• Determine successful methods to inactivate 

autoreactive immune cells in autoimmune 

disease. T-cell antagonists, mucosal tolerance, 

and methods to promote lymphocyte deletion 

are likely possibilities.

• Determine the role of innate immune mechanisms in immune and allergic diseases and 

devise therapeutic interventions.

• Establish improved surrogate markers to 

measure disease activity and response to 

therapy in diseases such as rheumatoid 

arthritis, multiple sclerosis, scleroderma, 

systemic lupus erythematosus, and 

Sjögren’s syndrome.

“Basic research will yield information that 

benefits the treatment and diagnosis of all 

autoimmune diseases and represents the most 

promising approach to finding a cure.”

Virginia T. Ladd, R.T.

American Autoimmune 

Related Diseases 

Association
Infectious Diseases

and Emerging 

Infections

Sexually transmitted diseases (STDs), including

HIV/AIDS, require a continued concentrated

research effort. Many of the STDs are more difficult to detect in women than in men and, in many

ways, these diseases affect women more severely. As 

a consequence of STDs, women may experience infertility, tubal pregnancy, genital cancer, early fetal loss,

and congenital or perinatal infection. Efforts should 

be continued to reveal more about the microbial and

behavioral etiology of these infections, their differential effects on women across the life span, measures

women can take to prevent contracting them or prevent their progression to later stages, and the effects 

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

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the infectious diseases field:

Basic Science

• Funding by the National Institute of Allergy 

and Infectious Diseases of STD centers that 

are focusing on an examination of the 

vaginal ecosystem.

• Characterization of the endogenous defense 

systems of the vagina and cervix. 

• Vaginal immunology and physiology, including 

an examination of normal and abnormal vaginal

ecosystem responses to preventive and therapeutic agents.

• Development of single-dose azithromycin for 

treatment of chlamydia.

• Research on mucosal factors in relation to STDs.

Epidemiology

• Epidemiologic research has highlighted both the

extent of the STD epidemic in the United States

and its consequences.

• Understanding the epidemiology of STDs and 

HIV is the finding that the diagnosis and treatment 

of STDs decreases the risk of HIV transmission

• Natural history studies of HIV in women have

helped determine how HIV is acquired and 

the appropriate clinical utility and prognostic 

significance of viral load and CD4 counts. 

The gynecologic manifestations of HIV are also 

being defined. The risk factors for heterosexual 

transmission of HIV are now better defined.

Clinical practice triumphs of the past 5 years 

are evident in the availability of new diagnostic 

tests and new drugs, including antiretrovirals 

(especially protease inhibitors).

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Epidemiologic data have helped to describe 

the occurrences and transmission of STDs and 

have helped bring about an increased sensitivity 

to the importance of behavior as an area that 

should be studied and addressed.

Scientific perspective — No longer is the 

vagina viewed, in research terms, merely as a 

repository for semen and a vessel for fetal and/or 

microbial growth, but rather as a complex ecosystem that should be studied in this context in 

order to advance biomedical knowledge about 

the infectious diseases that afflict women.

RESEARCH 

RECOMMENDATIONS

Basic Science

• Focus STD research on the human vagina 

to increase knowledge about the vaginal ecosystem: the “normal” state; alterations caused 

or enhanced by exogenous factors; effects of 

the menstrual cycle on disease; effects of the 

frequency of intercourse, with single and multiple partners, on disease; and changes in the 

vaginal ecosystem across the life span.

• Focus research on primary prevention tools 

on the effectiveness of exogenous hormones, 

topical microbicides, barrier methods, and 

vaccines as primary prevention of STDs, 

including HIV.

• Address microbial, host-genetic, and 

host-immunologic factors in the pathogenesis of STDs.

• Elucidate the pathogenesis of HIV/AIDS 

in women and include the study of the 

influences of hormonal and other 

natural defenses.

• Continue and increase research to prevent 

the myriad of adverse outcomes of pregnancy

caused by STDs and HIV. Conduct research on 

infertility, its causes, and methods to reverse it.

• Study the potential effects of hormonal birth 

control methods on a woman’s susceptibility 

to infection.

Epidemiology

• Conduct followup studies to determine the 

long-term sequelae of vaccines, treatments, 

and disease progression.

• Conduct research to determine whether 

a relationship exists between race-based 

factors and specific infectious diseases.

Clinical Practice

• Use clinical trials on microbicides and other 

barrier methods to define the efficacy, safety, 

and long-term sequelae of STD and HIV 

therapy, not only on the “typical” patient 

but also on pregnancy and neonatal outcome.

“. . . the need for woman-controlled methods 

of STD and HIV prevention has only recently 

been recognized as a priority, and much remains 

to be done to move this issue to the forefront 

of the women’s health agenda.”

Amy Allina

Reproductive Health 

Technologies Project
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VOLUME 1

• Conduct studies on patients with multiple 

infections.

• Continue research to find cures for viral STDs 

and HIV, to develop methods to combat microbial

resistance, and to develop treatments and vaccines

to prevent or eradicate these infections entirely.

• Study the consequences of inadequate comprehensive prevention and therapy for STDs and 

HIV in prisons.

• Study the impact of needle exchange programs 

on the spread of HIV.

Behavior and Education

• Develop a catalog of sexual behaviors as a 

base for any intervention strategy.

Other Diseases

• Study other women’s health issues related 

to infectious diseases including urinary tract 

infections, tuberculosis, the relationship of 

chlamydia to heart disease, chronic fatigue 

syndrome, malaria, Group B strep, bacterial 

vaginosis and other nonsexually transmitted 

vaginal diseases, hepatitis C, H. pylori, infectious etiologies of rheumatoid diseases, toxic 

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

• Participate in cooperative research and information sharing with other countries regarding

emerging infections.

Mental Disorders

Although major mental disorders affect 

women and men to almost the same extent,

depression, anxiety disorders, and eating 

disorders affect women more often than men. Across

societies and social contexts, symptoms of depression

and anxiety as well as unspecified psychiatric disorders

and psychological distress are more prevalent among

women, and women are more likely to have more 

than two disorders. Anorexia nervosa and bulimia 

nervosa occur 8 to 10 times more frequently in women

than men; together they affect 0.5 to 2 percent of adolescent girls and young women, and the prevalence of

both is increasing. Panic disorder occurs about twice 

as often in women as in men and 2 to 3 times as many

women as men are affected by phobias. Anxiety disorders affect 2 to 3 times as many women as men and 

are significantly more prevalent in girls than in boys,

which leads to higher incidence of depression in

women than in men. Anxiety disorders rank as the

most prevalent forms of mental illness in the United

States, affecting more than 20 million Americans.

Women are prescribed and use psychotropic medication at twice the rate of men.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the mental disorders field:

• The possibility that estrogen’s interactions with 

the circadian pacemaker may be involved in 

seasonal affective disorder and rapid-cycling 

bipolar disorder.

• Clinical depression can have a compounding 

deleterious effect on a person’s general health. 

One study prospectively examined whether a 

major depressive episode increases the risk of

myocardial infarction, finding that people who 

had been diagnosed with a major depressive

episode 10 years earlier were found to have 

a fourfold increased chance of having a heart 

attack during the ensuing 10 years.

• NIMH-supported research focusing on four 

of the most serious anxiety disorders: panic 

disorder, posttraumatic stress disorder (PTSD),

obsessive compulsive disorder (OCD), and 

phobias; new, effective therapies offer significant relief for most of these disorders.

• Studies of women victims of violent crimes showing that cognitive-behavioral interventions can

reduce post-trauma problems and relieve anxiety

and depression that can limit daily activities.

(Unfortunately, few women receive such therapy.)

• Selective serotonin reuptake inhibitors (SSRIs),

such as Prozac, to alleviate symptoms of OCD 

and to treat depression.

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

Mental health problems of females and males: Worldwide percentage of DALYs* lost. (*DALY - Disability Adjusted Life Year)

Source: Adapted from the World Bank, 1993, in Desjarlais et al. World Mental Health 1995.

FEMALES

Alcohol

Dependence

3% Alzheimer/

Dementia

15%

Depressive

25%

Drug 

Dependence

3%

Epilepsy

9%

Other

17%

Psychoses

7%

PTSD

7%

Self-inflicted

Injury

14%

MALES

Alcohol

Dependence

18%

Alzheimer/

Dementia

11%

Depressive

10%

Drug 

Dependence

7% Epilepsy

10%

Other

16%

Psychoses

7%

PTSD

3%

Self-inflicted

Injury

18%
49

VOLUME 1

• Successful behavioral interventions developed to

address the risk factors of specific groups with

increasing rates of HIV transmission, including

women and people with severe mental illness.

• Refined methods for the early detection of cognitive impairment in people infected with HIV 

who have no other medical symptoms.

• Scientific understanding of the biochemical events

that take place in the brain and central nervous

system during various stages of HIV infection.

• Animal models that permit closer investigation 

of different aspects of HIV infection of the central nervous system.

• Treatment of mental disorders that are comorbid

with physical disorders has been found to reduce

hospitalization and rehabilitation services and to

improve functioning.

RESEARCH 

RECOMMENDATIONS

• Study mental disorders across the life span.

Encourage research on the interactions among 

biological, psychological, and social factors 

related to mental disorders across the life 

span of women.

• Identify the social, developmental, and biological 

factors that predispose adolescent girls and young

women to mood, eating, and anxiety disorders.

• Explore the findings that levels of neuroactive 

peptides, such as cholecystokinin (CCK), may 

be altered in women with bulimia and that lower

levels of this peptide also correlate with higher

scores on measures of anxiety and anger.

• Study the long-term effects of violence and 

victimization. Research 1) psychological and 

biological effects of sexual assault in childhood 

and 2) interventions designed to prevent and/

or treat the long-term mental health effects of 

experiencing abuse and violence, especially 

so that women can engage in self-protective 

health behavior.

• Conduct research on the co-existence of drug

dependence with psychiatric disorders, especially depression, PTSD, anxiety disorders, 

and eating disorders.

• Study the effects over time of psychotropic 

drugs and hormones.

• Examine why female children in some families are resistant to mental disorders such as 

eating disorders.

• Examine not only the relationship between drugs

and alcohol and mental disorders and mental 

disorders with physical disorders, but examine 

the relationships among mental disorders.

• Study reproductive hormones and their role 

in women’s mental health, especially during 

the critical life transitions — menarche, 

pregnancy, postpartum, and menopause.

• Study mood and mental illness associated with

menopause and how major mental illnesses 

are affected by changing gonadal hormones.

• Investigate the effect of hormone replacement 

on mood.

• Identify, prevent, and treat the serious mental 

illnesses in women who are overburdened by 

the added responsibilities of caregiving resulting from changes in the health care and social 

services systems.

• Investigate how women and men vary in 

addictive behaviors ranging from drugs 

to food.

• Study the causes, prevention, and treatment 

of all forms of depression with emphasis on 

bipolar disorder.
50

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

• Investigate the role of steroidal hormones 

in mental disorders.

• Integrate cross-disciplinary research from molecular level through societal level. Prime topic 

areas for cross-disciplinary collaborations in

women’s mental disorders include AIDS/HIV,

abuse, PTSD, and depression.

• Conduct mental disorders research outside the 

traditional clinical settings in which women seek

treatment more frequently than men — for example, differing brain development in boys and girls,

studies of mental disorders of poor women living

in the community, and mental disorders studies 

in jails, domestic violence centers, and primary

health care settings.
Neuroscience

Neuroscience research is expanding rapidly

because of the refinement of theories and

principles, advances in genetics and molecular biology, and new imaging techniques. New understandings about genes and their expression, as well as

the activities of neurotransmitters, nerve growth factors, and other signals, are opening new avenues for

study. With the increased attention given to research 

on women’s health and to gender differences, studies

using combinations of neuroanatomical and behavioral techniques have identified sex differences in the

manifestation of brain disorders and the influence of

reproductive endocrine disorders in women and men

suffering from a variety of diseases. Research has

expanded on the influence of hormonal states on

important behavioral function such as cognition 

and on conscious emotion in health and disease.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the neuroscience field:

Development of the Brain and Nervous System

• Explorations of genetic and environmental 

influences have begun.

• The defective gene responsible for about two 

dozen neurological disorders has been identified, 

as has the chromosomal location of the defect 

in 50 to 100 — in the muscular dystrophies, 

some forms of mental retardation, manicdepression, and other neurological disorders.

• New evidence has been found for genetic imprinting in cognition and behavior.

• Personality effects in Turner’s syndrome has been

discovered, depending on whether the X chromosome is inherited from the mother or father.

• Mutations in mitochondrial genes cause rare 

neurological disorders.

• Communication between the endocrine system 

and the nervous system seems to cause anatomical differences in the developing brain.

• Along the hypothalamic-pituitary-adrenal 

(HPA) axis, responses to stress and to changes 

in circadian and reproductive cycles stimulate 

hormone production.

• New developments in imaging techniques 

enable the examination of functional neuroanatomy and the effects of therapies on the brain.

Sex Differences in Cognition and Effects of Hormones

• Scientific evidence has demonstrated the effects 

of sex hormones on adult cognition.

• Estradiol and progesterone have shown important

effects on adult brain structure and function.

Sex Differences in Manifestations of Brain Disorders

• Reproductive hormones (gonadal steroids) may

play an important role in pathophysiology and 

possibly treatment.

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

• Levels of ovarian hormones are linked to timing

and incidence of migraine headache and epileptic

seizures, as well as to sleep disorders (especially

sleep apnea) and torticollis.

• Meningiomas and neurofibromas have estrogen 

and progesterone receptors, and these neoplasms 

are sensitive to hormone levels.

• Sex differences exist in the manifestations of 

Alzheimer’s disease.

• Estrogen and HRT affect the frequency and 

severity of symptoms of depression, anxiety, 

and eating disorders; interactions of HRT 

with antidepressants and tranquilizers.

Sex Differences in Sensory Perception and Pain

• Sex differences exist in response to noxious 

stimuli, trauma, and the experience of pain, 

with females often reporting higher pain levels 

than males for the same stimulus intensity.

• Estrogen appears to induce analgesia through 

a different pathway in female mice than in 

male mice.

• Sex-linked genes are associated with nonopioid

analgesia in female mice.

• Sex differences are evidenced in coping strategies,

internal responses to pain, endogenous pain 

modulation, and reactions to pain medication.

Sex Differences in Balance and the Vestibular System

• Women and men often differ in their organization of body movement, which is possibly related 

to hormone levels and which may then place

women at greater risk for falls in old age.

• Some younger women experience falls that 

appear to be linked to hormone cycles.

• In the forebrain, ovarian hormones affect 

the nigrostriatal system and the cerebellum, 

as well as motor coordination.

Methodological Developments

• The combination of basic and clinical neuroscience methodology has enabled examination 

of sexual dimorphism developmentally. 

• Neuroimaging techniques, when combined with

clinical and neurocognitive assessment, are powerful

tools for identifying the mechanisms for sex differences in healthy brain function and in specific disease states; investigators using these technologies

are now able to extend and test hypotheses that

have implications for intervention.

RESEARCH 

RECOMMENDATIONS

• Raise awareness in the neuroscience research 

community about the importance of sex differences and hormonal influences on all aspects 

of brain function.

• Research basic mechanisms to develop better 

prevention and treatment strategies.

• Focus on attention to life span issues, developmental stages, and hormonal states.

• Study the neurobiology of interactions of gender

and gonadal hormones with endocrine, immune,

and other systems and disorders.

• Explore the impact of social and physical environment on neural development and function.

“. . . hormones affect epilepsy and epilepsy 

affects hormones, and there is a relationship 

between hormones and seizures at puberty, over 

the menstrual cycle, and at menopause. . .”

Linda Lindahl 

Epilepsy Foundation 

of America
Oral Health

Most oral problems are “complex” diseases

in that the manifestation of the condition

is the result of multiple genes and gene

susceptibility factors interacting with behavioral and

environmental variables. A variety of demographic, general health, economic, social, and behavioral factors may

be operative in placing subgroups of women at high

risk for development of oral diseases. These factors

include extended longevity, experience with multiple

chronic conditions, medications, cognitive impairments, compromised functional status, and physical

confinement, each of which can induce biological or

behavioral changes that adversely affect oral health.

Because oral problems are typically repetitive and

cumulative across the life span, disabling and handicapping outcomes are maximized among people in 

the later stages of life.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the oral health field:

• Saliva is used as an investigational aid to monitor

levels of hormones and therapeutic medications. 

• Poor maternal periodontal health increases an

infant’s potential for low birthweight and for

preterm or premature birth.

• Epidemiological findings indicate a nearly twofold risk for fatal myocardial infarction and stroke

for persons with established periodontal disease.

• Female dental patients respond more favorably

than males to kappa opioid analgesics for control

of postoperative pain.

• Studies of oral HIV in the areas of mucosal immunity, synthetic drugs and vaccines, and innovative

drug delivery systems will be of benefit to women

as the fastest growing AIDS population.

RESEARCH 

RECOMMENDATIONS

Biomimetics

• Study the effect of hormonal status on the 

efficacy of guided bone and tissue engineering procedures.

Diagnostic Markers

• Investigate the utility of saliva as a matrix for 

studying biological markers important to women’s

health and diseases.

• Determine how best to utilize oral examination

findings and the dental clinic encounter in domestic violence, child abuse, and eating disorders

intervention programs.

• Explore whether dental radiographs can be useful 

in identifying aberrant skeletal bone changes.

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

Sjögren’s Syndrome and Autoimmune Diseases

• Investigate the role of gender in autoimmune conditions, including the role of sex hormones in

induction and perpetuation of these conditions.

• Study gender-controlled transcription differences

that influence autoimmune disease penetrance. 

• Conduct research on the impact of hormonal 

therapy on women with Sjögren’s syndrome 

and other autoimmune conditions.

• Identify appropriate and sensitive clinical outcome measures for the exocrine dysfunctions 

associated with Sjögren’s syndrome. 

• Conduct controlled clinical trials testing new 

biological therapies for Sjögren’s syndrome.

Pain

• Study the relations among fluctuations in 

reproductive hormones and pain experiences

including cognitive, emotional, and behavioral components.

• Investigate the hormonal influences on nociception and pain modulation pathways, and 

investigate the effects of replacement therapies 

on pain and analgesia.

• Examine women’s stress response to pain 

and coping behaviors. 

• Study sociocultural effects on women’s 

responses to pain across the life span 

and in different cultural milieus.

Prevalence of Select Oral Conditions Among Women 18 Years of Age and Older: United States 1988-94.

Sources: National Health and Nutrition Examination Survey III

0

20

40

60

80

0

10

20

30

40

50

46.9

Percent of Women

63.8

67.1

49.5

28.9

Tooth Loss1

Moderate 

Peridontal Disease2 Gingivitis

Gingival

Recession3

1.) Loss of 1 or more teeth excluding 

third molars.

2.) Loss of attachment of 2mm or more.

3.) Gingival recession of 2mm or more.

Teeth that Are Decayed, 

Missing Due to Decay, or Filled

Percent of Teeth

Caries Experience
55

VOLUME 1

• Examine predictors of chronic pain development 

in women, including diminished activation of

endogenous pain control systems.

• Conduct basic research to examine the effects of

estrogens and other hormones on nociception 

and pain modulation pathways.

• Study the interactions between oral taste and 

pain sensations, particularly as they relate 

to painful oral lesions and oral pain in the 

absence of visible oral pathology, as in burning mouth syndrome.

• Explore the mechanisms and models (both 

animal and human) underlying gender differences in responses to noxious stimuli 

and analgesic medications.

• Study the role of genomic and nongenomic 

mechanisms mediating actions of gonadal hormones on pain perception and pain control. 

• Investigate the role of steroid hormone response 

elements in regulation of gene expression in 

pain pathways.

Temporomandibular Disorders

• Conduct studies to elucidate the etiology and

pathogenesis of TMDs, including the contributions of segmental versus heterosegmental

hyperalgesia to TMD myogenous pain. 

• Design evidence-based research studies to 

determine optimal treatments and outcomes 

for specific TMD clinical presentations.

HIV

• Investigate the prevalence of oral lesions among

infected women and determine their prognostic 

significance for HIV disease progression. 

• Determine if there are gender differences 

in response to, and compliance with, oral 

lesion therapies.

• Explore the relation between oral and vaginal 

candidiasis and study the effects of oral versus systemic antifungal therapies on oral 

candidal lesions. 

• Determine the relationship of oral diseases 

in HIV-infected women and their children, 

including perinatal transmission.

• Investigate the barriers to accessing oral care 

for HIV-infected women and evaluate the 

resultant effects on health and oral health.

Interrelationships of Oral and Systemic Disorders

Osteoporosis

• Study the relationship of periodontal disease, 

alveolar bone loss, residual ridge resorption,

osteopenia, and osteoporosis.

• Explore how stress, coping behaviors, and 

depression modify the relationship among 

oral bone loss, osteopenia, and osteoporosis.

• Determine whether bone density in the 

oral cavity correlates with systemic bone 

mineral density.

• Determine if common therapeutic strategies 

can be exploited for treating alveolar bone 

loss and systemic bone loss.

“An alarming shortage of research-trained, 

full-time female dental faculty exists at our 

dental schools.”

Debra Studen-Pavlovich, D.M.D.

American Association 

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

• Determine the influence of hormonal status 

and hormone replacement therapy on oral 

bone loss and tooth retention.

Diabetes

• Determine the role of periodontal infection 

as an aggravating factor for diabetes mellitus 

in women. 

Cardiovascular Disease

• Study periodontal infection as a risk for 

CVD in women.

Spontaneous Preterm Births

• Study fundamental mechanisms that combine 

oral disease measures and microbial, immunological, and inflammatory parameters to understand how oral infection may modify the 

maternal-fetal interaction.

• Conduct population-based, prospective studies 

to assess the independent contribution of periodontal infection to the risk of spontaneous

preterm birth (SPB).

• Carry out intervention studies to determine

whether periodontal therapy reduces the 

incidence or morbidity associated with SPB.

• Expand animal studies on the underlying 

mechanisms of SPB and the influence of 

distant infection on pregnancy.
Pharmacologic 

Issues

Clinically significant pharmacodynamic 

differences in drug-induced responses 

exist between men and women. The changing hormonal milieu in postmenopausal women in

relation to their overall health and the occurrence of

certain diseases requires extensive study. Despite the

impressive advances in policies regarding the participation of women as subjects in research and analysis 

of data for gender effects, gaps in knowledge remain

regarding the behavior of drugs in women. Areas where

much additional research is needed include mechanisms of drug action, which include pharmacokinetics

(PK), pharmacodynamics (PD), and pharmacogenetics;

biological and molecular bases of pharmacological

effects such as ion channels and membrane transporters; chronopharmacology; and modulators such 

as sex steroid hormones that can influence PK and

receptor sensitivity in target end organs. Over-reliance

on traditional male-oriented medical practices may 

ill serve women and, in some instances, may actually

harm them.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the pharmacology field:

• Detailed scientific information relating to drug

pharmacokinetics and pharmacodynamics in

women, as a result of women of all ages being

included in all phases of clinical trials.

• Progress in identifying and understanding the 

role of various metabolic enzymes in causing 

gender differences in PK or PD.

• Surrogate endpoint information related to overall health and the occurrence of certain diseases,

provided by studies in postmenopausal women

such as the Postmenopausal Estrogen/Progesterone

Intervention (PEPI) trial.

• Major research efforts to identify and assess 

impacts on various estrogen receptors, the influence of such receptors on PD variation, and newer

forms of hormone-analog molecules such as the

selective estrogen receptor modulators (SERMs).

RESEARCH 

RECOMMENDATIONS

• Use whole animal studies to evaluate therapeutic

efficacy and potential side effects of drugs.

• Develop decision-analysis tools to help determine

when, and under what circumstances, PK and PD

studies should be performed: Assess gender-related

PK and PD differences in multiple populations

including women with childbearing potential,

pregnant women, lactating women, perimenopausal women, menopausal women, and senior

women. Perform research into the mechanism 

of these differences to enable identification and

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

prediction of gender differences that may result 

in increased drug toxicity or lack of responsiveness in either sex.

• Investigate the role of sex hormones as possible 

causes of receptor sensitivity. Differences in 

receptor sensitivity need to be studied, particularly with regard to effects on the QT interval,

which may differentially predispose women to 

cardiac arrhythmias. 

• Develop improved methods for collecting and 

analyzing data on the use of pharmacologic 

agents in pregnancy with respect to safety and 

efficacy for the mother and safety for the fetus.

• Examine the broad spectrum of possible 

drug-drug and drug-nutrient interactions 

both for available pharmacologic agents 

and for those currently in clinical trials.

• Examine underlying mechanisms that contribute to gender differences in drug action 

and disposition. Define the pharmacokinetics,

pharmacogenetics, chronobiology, modulators, 

biologic and molecular factors, and pharmacodynamics of pharmacologic agents across the 

life span and across racial and ethnic groups.

• Conduct preclinical research in the development and validation of in vitro and whole 

animal models to test and predict gender 

specific pharmacologic differences.

• Evaluate PK and PD of new drugs by incorporating research on potential adverse effects on the

pregnant woman, the fetus, and the newborn.

Develop methods of assessing subtle effects, 

such as possible neurodevelopmental and 

immunologic impairment in children.

• Ensure that attention to studying mechanisms 

of pharmacologic effects become an integral 

component of the review process across institutes and offices whenever a pharmacologic 

agent is part of a study protocol for prevention 

or treatment of a disease or condition.

Components of Pharmacologic Effects

• Examine the underlying mechanisms that 

contribute to gender differences in drug effects 

and disposition including membrane transport

pumps, ion channels, chronobiology, metabolic

enzyme differences, sex hormone receptors, 

drug interactions between hormonal contraceptives and hormone replacement therapy, 

and drugs affecting chemical compounds 

such as the neurotransmitters.

• Carry out basic and applied research on pharmacokinetics, pharmacodynamics, and the 

importance of combining PK and PD data:

– Develop decision-analysis tools to help determine when, and under what circumstances, 

PK and PD studies should be performed. Assess

gender-related PK and PD differences in multiple populations including women with childbearing potential, pregnant women, lactating

“To provide optimal pharmaceutical care, 

pharmacists should be aware of the ethnic and racial

composition of their patient populations and the 

distinctive characteristics that may elicit ethnic and

racial differences in pharmacologic responses to 

medicines, as well as the psychosocial and economic

parameters that influence drug use or misuse.”

Gloria J. Nichols, Ph.D.

Catherine A. White, Ph.D.

University of Georgia

College of Pharmacy
59

VOLUME 1

women, perimenopausal women, menopausal

women, and senior women.

– Study the effects of drugs in women across 

the life span in relation to drug absorption, 

distribution, metabolism, and elimination, 

with special focus on postmenopausal women

(with and without hormone replacement 

therapy) and senior women who experience

changes in organ function. 

Gender Studies

PK and/or PD studies for

gender effects in phase

1 and 2 studies

• Prior information • Critical/lifesaving

• Intended use • Routes of elimination 

• Narrow therapeutic index drugs • Others

• Non-clinical studies

Signal of Gender Effect?

Safety and Efficacy Gender Subset Analyses

Targeted PK and/or PD

studies to confirm gender effect

• Go to phase 2B/phase 3 clinical trials

• Do prospectively designed population PK/PD gender effect?

• Conduct appropriately

designed phase 2B or

phase 3 clinical trials 

with appropriate

dosing

• Conduct ordinary

phase 2B/phase 3

clinical trials

• No different doses

between genders

Unexpected Confirmed

findings

Additional

studies?

Yes

Yes Yes

No

No No
60

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

• Conduct research on other specific topics including:

– Conventional hormone therapy vs. SERM.

– Long-term effects of lifetime estrogen 

exposure.

– Gender differences in response to 

chemotherapy.

– PK and PD of specific drugs or drug 

classes such as chemotherapeutic agents, 

and potassium channel blocking antiarrhythmic drugs.

• Examine drug-drug and drug-nutrient interactions.

• Carry out basic and applied research on pharmacogenetics:

– Research studies are needed that have 

sufficient statistical power to determine 

the nature of the interaction between 

gender and genetic polymorphism.

– The role of CYP 1A2 and 3A4 in gender 

differences of drug metabolism, as well as 

the interface between these isoenzymes and

estrogen metabolism, induction, or inhibition

merits further investigation with respect to oral

contraceptive failure and cancer induction.

– There is evidence that CYP 3A4 activity is

greater in younger women compared with 

men and postmenopausal women. Demonstrated decreased metabolism in postmenopausal women may make them more liable 

to adverse effects of certain medications. 

Careful study of this possibility is needed.

– Study the posited gender-related differences in

CYP 1A2 expression. The potential inhibition 

of CYP 1A2 by estrogen is demonstrated by

decreased caffeine metabolism in women 

receiving estrogen replacement therapy.

• Carry out basic and applied research on membrane transporters. Study potential gender-specific

expression of p-glycoprotein and MRP related drug

efflux pumps and other membrane transporters.

Such differences have important value for decisions

regarding selection of drug type and dosage (e.g.,

in cancer chemotherapy).

• Carry out basic and applied research on ion channels. Further pre-clinical and clinical research is

needed to better define differences in sodium and

potassium channel sensitivities between men and

women that may explain differential adverse effects

observed following intake of certain medications.

• Carry out basic and applied research on modulators. Examine differences in receptor sensitivity

possibly caused by sex hormones.

• Carry out basic and applied research on

chronopharmacology:

– Study gender differences related to biologic

rhythms and their application to efficacy 

of drugs. 

– Study the chronopharmacology of disease

because biologic rhythms may change 

during the disease process and affect 

drug dosing requirements.

Preclinical Studies

• Focus special attention on the continued development of animal and other models to predict 

with some accuracy the reproductive and developmental effects of drugs in humans.

• Evaluate therapeutic efficacy and potential side

effects through whole animal studies.

• Place receptor and cell-signaling research in 

the context of the whole organism, including 

physiological and therapeutic considerations 

in animal research.
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VOLUME 1

Drug Use in Pregnancy

• Develop improved methods for collecting and 

analyzing data on the use of pharmacologic 

agents in pregnancy with respect to safety and 

efficacy for the mother as well as the fetus.

• Develop scientifically valid and rigorous 

methods of evaluating potential risks in 

humans including frequency of structural 

and functional birth defects and reproductive 

effects such as rates of spontaneous abortion.

• Perform critical research to determine the 

best systems to link data from a mother to 

her newborn. This should be followed by 

implementation of such systems for Medicaid data, at HMOs, and at academic centers.

• Perform clinical trials in pregnant women for 

those drugs commonly used by pregnant women,

particularly in the second and third trimester.

These trials should address pharmacokinetics 

and dosing recommendations. All trials of drugs 

in pregnant women should collect maternal safety

data for the purpose of comparison with the safety

profile of the drug in nonpregnant women.

• Research birth anomalies that are more difficult 

to detect, such as those that are neurodevelopmental or immunologic.

• Study the effects of maternal medications on 

the breast-feeding infant. Drug concentration 

measurements in breast milk should be considered for inclusion in studies of the PK and PD 

of new drugs, and methods should be developed to predict infant exposure levels.

Reproductive Health

Historically, “women’s health research” was

generally limited to the study of obstetrics

and gynecology. In the late 1970s, societal

shifts, notably feminist concerns about women’s interactions with the medical system, resulted in a broader

national research agenda that encompassed a more

comprehensive definition of women’s health. This 

drew attention to the lack of research on major issues

such as cardiovascular disease and cancer in women,

and the problem of ineffective or inappropriate treatment of diseases and conditions in women.

ACHIEVEMENTS

Recent research has contributed the following

knowledge to the reproductive health field:

Pregnancy

• The biology and management of pregnancy.

• Research on infectious diseases of pregnancy and

preterm labor and on other pathophysiologic

aspects of abnormal pregnancy. 

• Effects of somatic disease on pregnancy. 

• Genetic testing and other diagnostic tests 

providing information on prevention 

of malformations.

• The relationship of implantation (normal 

vs. abnormal) and fetal development.

• External factors with potential effects on pregnancy, including environmental factors, diet 

and nutrition, exercise, smoking, violence, 

and the effects of hormones and medications.

• Diagnostic systems that are better focused on 

and address the needs of specific populations.

Contraception

• Knowledge of contraceptive use behavior and 

generating new contraceptive technologies. 

• Availability of Norplant (levonorgestrel subdermal

implants), Depo-Provera (medroxy-progesterone

acetate injection), and the female condom for 

pregnancy prevention.

• Advances in microbicides and spermicides and 

in their use among women.

Infertility

• Greater awareness that infertility is a “couple 

problem” rather than a female problem, and 

recognition that male infertility is also a 

women’s health problem.

• Genetic causes of male infertility with the 

potential for heritable infertility. 

• Ovulation induction based on developing 

knowledge of ovarian physiology.

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• Better selection of treatments for infertility. 

• Knowledge about ectopic gestation; new treatments, such as methotrexate, are improving the

medical management of ectopic pregnancy and

reducing the need for surgical intervention.

Reproductive Tract Diseases and Disorders

• Promoting greater awareness of reproductive tract

diseases and disorders and their prevalence and

morbidity, including myoma, abnormal uterine

bleeding, premenstrual syndrome, endometriosis,

pelvic pain, and pelvic floor relaxation.

• New information on abnormal biology of 

reproductive tract diseases and disorders and 

in medical and conservative surgical therapies;

recently identified steroid receptor subtypes 

may hold clues to development of diseases 

and approaches for treatment.

RESEARCH 

RECOMMENDATIONS

Pregnancy

• Conduct more research to better understand 

the context of maternal health and pregnancy 

with special attention to preterm labor, ectopic 

pregnancy, intrauterine growth retardation 

(IUGR), preeclampsia, spontaneous abortion, 

labor and delivery, and lactation.

• Study basic physiology, management, and 

sequelae of pregnancy.

• Develop technology for improved monitoring 

of pregnancy — genetic testing, medical and 

surgical interventions, and other alternative 

therapeutic modalities.

• Examine external factors extensively affecting

women’s physical and psychological health —

lifestyle, environment, diet, exercise, alcohol, 

smoking, violence, and pharmacology of 

prescription and over-the-counter drugs.

Sex and Contraception

• Focus on research, based on current knowledge of

contraceptive use, to increase responsible contraceptive and sexual behavior (decisionmaking and

compliance), especially among adolescents and

women with gynecological infectious diseases.

More research is needed regarding the role of 

contraceptives in the prevention of STDs.

• Target the biology of the human oocyte to 

develop new contraceptives.

• Optimize and develop contraceptive options 

for specific circumstances and populations (e.g.,

women with STDs, AIDS/HIV-positive status) 

and study the long-term effects and interactions 

of existing and emerging contraceptives.

Fertility and Infertility

• Learn from biology of the reproductive system 

to focus on developing and improving diagnostic

and therapeutic measures.

• Understand the etiology and pathophysiology 

to improve fertility and reduce infertility.

• Select the appropriate treatment and management for specific populations.

• Research the behavioral effects of infertility, e.g.,

reducing the negative sequelae of assisted-reproductive technology and other infertility treatments

and their effects on gamete donors and surrogate

mothers, social concerns of reproductive ethics,

and socioeconomic effects of multiple births.
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Benign Diseases and Disorders

• Study the etiology and pathophysiology of each 

of the above diseases or disorders leading to the

evolution of safer and more acceptable treatments.

• Examine the long-term effects of these gynecological

diseases and disorders and their treatments.

• Discover genetic and molecular factors in disease

development and identify noninvasive markers 

of disease activity.

• Research nonsurgical management of the above 

diseases and disorders.

Maturation and Aging

• Study consequences of maturational changes 

of the hormonal axes and their effect on fertility,

menopause, and hormone dependent diseases 

and behavior.

• Study hormone replacement therapy (HRT), 

both existing (estrogen and/or progesterone) 

and potential (androgens, DHEA, etc.) — their

roles in development of novel treatments based 

on hormone actions and interaction, including

receptor subtypes; safety and efficacy of therapy;

detection and reduction of adverse effects; effects 

on initiation, growth, or reactivation of hormone

dependent pathologies; and the impact on the

quality of life over time.

Urologic and 

Kidney Conditions

Diseases of the kidney and urinary system

have a major impact on women’s health.

Permanent kidney failure, called end-stage

renal disease, affects more than 120,000 women in the

United States alone. Treatment with dialysis or transplantation, although necessary to sustain life, does not

restore normal, or even near-normal, life expectancy.

The average death rate for end-stage renal disease

patients is approximately 25 deaths per 100 patient

years. Thus, at all ages and for both genders, kidney

failure results in a markedly shortened life expectancy.

Kidney disease is increasing in incidence in the United

States, where the number of new patients requiring

either dialysis or transplantation approximately doubled between 1985 and 1995. Particularly important

for women is an increase in the incidence of Type II

Diabetes Mellitus. Also important for women’s renal

health is the impact of pregnancy-related kidney disorders. Other forms of renal disease that are more frequent in women than men are analgesic nephropathy

and the nephritis associated with systemic lupus erythematosus. Women’s urological disorders are very

common, afflicting virtually all women at some point 

in their lives. While less frequently life threatening 

than renal failure, these conditions often have a 

major impact on the quality of life.

ACCOMPLISHMENTS

Recent research has contributed the following

knowledge to the field of urology:

• Recognition that dialysis dose, nutrition, vascular

access, and proper treatment of anemia are all

important considerations that affect end-stage 

renal disease patient morbidity and mortality.

• Development of new drugs for the prevention of

organ rejection in transplant patients.

• Development of new forms of insulin and advances

that facilitate intensive therapy. These include human

insulin produced through genetic engineering, better

techniques for blood glucose monitoring, and external and implantable insulin pumps that deliver

appropriate amounts of insulin.

• Improved characterization of the clinical presentation of analgesic nephropathy and of the specificity

of noncontrast computerized tomographic imaging

of the kidney for its diagnosis.

• New insights into immune cell activation and death,

pathways of tissue destruction, and modulators of

lymphocyte or target cell function in experimental

models of lupus, specifically the role of Fas and 

the Fas ligand, with the surprising demonstration that deficiency in this pathway accelerates

lupus nephritis.

• Subcategorization of pregnancy-induced hypertension as a heterogeneous entity comprised of 

several different subgroups including chronic 

renal disease, borderline chronic hypertension,

genetic susceptibility to hypertension, and 

genuine pregnancy-induced hypertension.

• Development of treatment guidelines on urinary

incontinence by the Agency for Health Care 

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Policy and Research and the American 

Urological Association.

• Diagnostic standards for genital prolapse, 

established by the International Continence 

Society and accepted by the American 

Urogynecologic Society and the Society 

of Gynecologic Surgeons.

• Acceptance and understanding that childbirth is 

a major etiological cause of pelvic floor disorders.

• Development of molecular genetic techniques to

characterize uropathogens that colonize the urinary

tract and track the course of individual infections.

• Increased understanding of behavioral risk factors.

• Availability of new pharmaceutical treatments for

interstitial cystitis.

RESEARCH 

RECOMMENDATIONS

• Attract more basic science researchers, from a 

variety of scientific disciplines, into these fields 

by workshops that target a variety of disciplines 

and by increasing funding for research and 

training programs.

• Establish the effects of chronic analgesic use on 

renal function, and the incidence of analgesic

nephropathy in the end-stage renal disease 

population in the United States.

• Initiate prospective observational studies on the

impact of pregnancy on renal function in women

with underlying kidney disorders and renal transplants. Studies should define the effect on both

short- and long-term renal prognosis, as well 

as pregnancy outcomes.

• Determine the causes of altered renal hemodynamics during pregnancy.

• Establish the optimum approach to hormone

replacement therapy in women with chronic 

renal insufficiency and end-stage renal disease.

• Expand research on the pathogenesis of lupus

nephritis to exploit current insights in inflammatory mechanisms and cytokine pathways.

• Improve strategies for preventing diabetic 

nephropathy due to Type II Diabetes.

• Conduct basic science research on bladder 

and pelvic floor disorders including physiology and pathophysiology.

• Develop and validate standard measures for 

assessment (baseline conditions and outcomes) 

for urinary incontinence, interstitial cystitis, 

and pelvic floor disorders.

• Initiate new (and utilize existing) longitudinal 

epidemiological and interventional studies using

diverse populations on urinary incontinence, 

pelvic floor disorders, and urinary tract infections

including the impact of childbearing and aging.

• Initiate valid and controlled clinical trials for 

the treatment and prevention of incontinence,

pelvic floor disorders, urinary tract infections, 

and interstitial cystitis. These clinical studies

should not be relegated to the industrial sector.

“Interstitial cystitis (IC) was considered, 

and still is considered by some urologists, as an 

‘hysterical female condition.’ Unfortunately, this 

blatantly incorrect label still haunts IC victims 

with the sufferer taking on average 4.5 years to 

get a correct diagnosis and often having to see an

average of five physicians before IC is diagnosed.”

Vicki Ratner, M.D.

Interstitial Cystitis 

Association
Reports of the Working Groups:

Sex and Gender Perspectives Throughout 

the Life Cycle — Summary of Recommendations

Prenatal, Infancy, 

and Childhood Years

NORMATIVE DEVELOPMENT

Because understanding normative development

allows for a clearer understanding of pathological processes, research that looks at 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.

Research Recommendations

• 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.

• 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 

AND PHARMACODYNAMIC

EFFECTS OF DRUGS IN

NON-ADULT, NON-MALE

POPULATIONS

Gaps in knowledge exist about the effects 

of prescription and over-the-counter medications,

xenobiotics, and herbal remedies on women and 

children. In researching these areas of pharmacokinetics and pharmacodynamics, a stratification 

must be adopted that addresses the differences 

of age, gender, and ethnicity. 

Research Recommendations

• Absorption, distribution, metabolism, and elimination of drugs, beginning early in the prenatal

stage and following 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.

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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, 

based on culture, gender, and age. 

Research Recommendations

• 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. 

Research Recommendations

• 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 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. 

Research Recommendations

• 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

PASSAGE OF DISEASE

Children become predisposed to diseases 

in the early stages of their development. 

Research Recommendations

• 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.
Adolescent Years

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 biological changes.

Although great diversity in race, culture, and age 

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. 

General Research Recommendations

• 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.

• Comprehensive guidelines for adolescent participation in clinical trials.

• A workshop to study the barriers and facilitators 

to adolescent research, including current guidelines, Institutional Review Board (IRB) approvals,

and ethical and legal issues for gathering data 

from this age group.

• Assess the legal, moral, and ethical issues 

involved in conducting clinical research in 

the adolescent population, possibly through 

the Institute of Medicine.

DEVELOPMENT 

ISSUES ACROSS THE

ADOLESCENT YEARS

Research should focus on:

• Biological development — how biology affects

behavior and how the immune system changes

body composition and affects behavior.

• Social development — how body development

affects social behavior.

• Psychosocial development.

• Environmental effects — how the environment

affects body composition and development.

• Cognitive development.

• Mental health.

RISK-TAKING BEHAVIORS

Research should concentrate on:

• Sexual behavior — primary and secondary prevention of pregnancy, implications for STDs 

and pregnancy, girls’ masturbation habits, the 

role of coercion in an adolescent girl’s sexual 

debut, and age of the sex partner and how 

that affects development.

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• Substance use and abuse.

• Other areas including violence, injury, suicide, 

runaways, homelessness, and a cross-sectional

study of girls in gangs.

PROMOTING HEALTHY

BEHAVIORS

Research should concentrate on:

• Nutrition — communicating healthy eating habits.

• Physical activity — how adolescent girls can 

be encouraged to get regular exercise and how 

to promote healthy behaviors like delaying 

smoking, alcohol use, and sex.

• Sexual health and hygiene.

• Oral health.

• Effective, accessible, user-friendly screening tools.

ADOLESCENT 

PARTICIPATION 

IN RESEARCH

Research should focus on:

• Normed assessment tools.

• Institutional Review Board issues around 

adolescent consent.

• Diversity.

• Inclusion in clinical trials.

• Support of secondary analyses.

• Supplements for ongoing studies.

COPING SKILLS

Research should focus on:

• Chronic disease.

• Family issues, including teaching parenting 

skills to teens.

• Life events.

• Violence.

• Resilience, including the skills needed 

to deal with emotions like anger.
Reproductive and

Middle Years

SEXUAL AND 

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 Recommendations

• 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.

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.

Research Recommendations

• 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, homeless shelters).

• Conduct epidemiologic studies to define the

diverse populations and their distinct health 

care needs.

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• 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.

Research Recommendations

• 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

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 in all studies, not just those directly

addressing pregnancy issues.

Research Recommendations

• Recognize and use opportunities to collect passive

data to study the effects of drug use on pregnancy.

• Include the investigation of effects of medical 

interventions in women of reproductive potential 

in existing clinical trials and followups.

• 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.
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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.

Research Recommendations

• 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 and 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 and increase genderspecific 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 and identify

gender-specific pharmacokinetics.

DES exposure — Continue research to determine 

the effects of second-generation exposure to diethylstilbestrol (DES), with special attention to 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 and cellular regulation

research with specific attention to defining the 

basic biology of these diseases and to identify 

components of their causes.

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 and

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 
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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.

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 coexisting factors such as violence, victimization, 

and psychiatric disorders.
Perimenopausal and

PostMenopausal Years

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 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.

RESEARCH 

RECOMMENDATIONS

The Menopausal Process

• Clarify and define the various stages comprising

the transition from premenopause to perimenopause to postmenopause.

• 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; 

specifically bleeding abnormalities, development 

of obesity in the menopausal years, and the role 

of the postmenopausal ovary on the manifestation 

of menopausal symptoms subsequent to morbidity.

• 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.

• Explore environmental, cultural, and lifestyle 

influences on menopause, including what constitutes optimal primary care for women in this

stage of life, the effects of physician training on 

the health care of menopausal women, whether

women would be better served if gynecology 

were separated from obstetrics, women’s needs 

and appropriate strategies for contraception 

during the perimenopause, and the influence 

of environmental agents on estrogen receptors.

Pharmacological Aspects of Peri- and Postmenopause

• Evaluate the effects of endogenous and exogenous

hormones on tissues and physiological processes 

of multiple target organs. 

• Continue and expand studies of hormone replacement therapy (HRT). Specific areas to be explored

include the effects of administering conjugated 

versus pure forms of estrogen and natural versus 

synthetic progestins; oral versus transdermal

administration; the schedule in estrogen-progestin

regimens; methods of reducing side effects and

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optimizing and 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.

• Research 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

• Explore the psychological aspects of menopause 

and the transition to menopause, including

women’s attitudes toward bleeding and the 

symptoms of menopause.

• Research the effects of caregiving in the menopausal years, including how the stress of this

increased burden affects the menopausal process 

and how caregiving responsibilities affect women’s

participation in preventive health practices and

clinical trials and other studies.

• Determine the attitudes, knowledge, and perceptions of women, health care providers, and 

society in general toward menopause and toward 

the aging processes, including examination of 

the barriers to health care in this period of life 

and how they can be overcome.

• Explore the psychosocial and the biomedical

aspects of genetic susceptibility testing, including 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 the health effects on menopausal 

women of such stressors as bereavement, 

abandonment, the “empty-nest” syndrome, 

and other forms of loss.

• Devise and implement 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.

• Undertake meta-analyses on data from prior 

studies on weight management and hysterectomy 

to maximize the value of the extensive research

that has already been conducted in this area.
Elderly and Frail

Elderly Years

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.

RESEARCH 

RECOMMENDATIONS

Social and Behavioral Issues

• Focus on changes in family and social structures,

caregiving roles, and new workforce services 

for women.

• Focus on the feasibility and intergenerational

impact of formal and informal caregiving: stress,

coping, training lay providers, and respite care.

• Promote personal choice and autonomy in 

living situations.

• Identify the antecedents and consequences of

mandatory elder-abuse reporting by physicians 

and nurses.

• Develop ways to empower older women in their 

use of health care, including second opinions,

mammograms, and clinical breast exams.

• Increase efforts in health promotion and disease 

prevention, including encouraging older women 

to participate in clinical studies and sharing

research results with these groups of women.

• Encourage research on the impact of managed care

on the health and well being of older women.

• Continue research on mobility and safety issues.

• Develop research on the use of assistive technologies.

Mental Health Issues

• Study gender differences in depression.

• Continue studies of alcoholism and other drug

abuse and dependence, including dependence 

on prescription drugs.

• Study effective coping strategies.

• Investigate dementias.

• Study the impact of living arrangements on 

mental health.

• Study the impact of chronic pain on mental 

and physical health.

• Study the impact of fears of death and dying 

and terminal pain.

Cardiovascular Illness

• Continue research on treatments and outcomes 

for men and women.

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Osteoporosis and Osteoarthritis

• 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.

• Identify biomarkers to predict osteoarthritis.

• Study strategies for delaying the progress 

of osteoarthritis.

• Concentrate on preventive strategies, i.e., 

increased calcium intake in adolescence 

and young adulthood.

Musculoskeletal Fitness

• 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.

Health Promotion Activities

• Target health promotion activities to increasing

appropriate exercise, boosting nutrition awareness and habits, and decreasing disability.

Pain and Its Impact on the Elderly

• Study the impact of chronic pain on physical 

health and find ways to relieve the chronic pain 

of comorbid conditions in older women.

Urinary Incontinence

• Study normal and abnormal bladder physiology, to suggest treatment for incontinence.

• Research adjunctive treatments such as pharmacologic therapy.

• Investigate behavioral interventions for 

persons at risk.

• 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.

Impact of Improved Health in the Elderly

• Undertake studies 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.

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 to discover 

whether older women are considered 

appropriate candidates for these devices.
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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

• Investigate whether there is a genetic basis for

chronic diseases or retention or loss of physical

functioning in old age.

Issues of Pharmacology and Aging

• 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

• Develop data-mining techniques to extract from

existing databases critical health information 

pertinent to the health of elderly women.

• Identify the toxic drug interactions associated 

with the use of concomitant medications, 

including the concomitant use of HRT.

• Develop more effective 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.

Reports of the Working Groups:

Differences Among populations of Women

throughout the Life Cycle — 

Summary of Recommendations

Prenatal Years

The role of population differences in successful

pregnancy outcomes has not been emphasized

in the research to date. Thus, while the studies of the physiology, biochemistry, pharmacology, and

genetics of pregnancy must continue to identify the

overall strategies for improving women’s health, the

challenge of improving the health of women must 

also emphasize the environmental, psychological, 

and population effects.

RESEARCH 

RECOMMENDATIONS

Observational Studies

• Study drug use and traditional practices among

pregnant women in diverse groups.

• Determine the behavioral basis of motivation 

for seeking prenatal care.

• Explore and define cultural sensitivity in acquisition of genetic information.

• Encourage greater concern with qualitative studies.

• Examine probable overutilization of technology 

for pre- and perinatal medicine.

Clinical Studies

• Build and incorporate community values in 

diverse groups into outcome measures.

• Compare susceptibility (needs) with strengths

(assets) in individuals and groups with regard 

to adverse fetal outcomes.

• Conduct long-term studies of environmental 

exposure in human groups and animal models, 

both preconceptually and in utero.

• Investigate the pharmacodynamics and pharmacokinetics of drugs in diverse groups.

• Conduct longitudinal studies of multiple 

approaches to prenatal health — a Preconceptional and Perinatal Health Initiative.

Genetic and Physiological Studies

• Explore the genetic differences among diverse

groups, with an emphasis on fetal outcomes.

• Coordinate genetic information with environmental differences.

• Investigate placental biology in diverse groups.

Educational Initiatives

• Educate the practitioner and the public to subpopulation needs by consensus, conference, 

and national programs.

• Use networking to engage appropriate selfidentifying groups.

• Use interdisciplinary education.

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Administrative Concerns

• Encourage investigations by recurrent regional

training programs.

• Sensitize DRG to applications involving diverse

human groups.
Infancy and 

Childhood Years

The infancy and childhood cohort is large 

and diverse. Problems encountered by this

group range from prematurity with multiple

congenital anomalies to postpubescent pregnancy. 

The understanding of many diseases and conditions 

of infancy and childhood has advanced greatly, but 

a comprehensive research agenda for this group 

is imperative.

RESEARCH 

RECOMMENDATIONS

Research Methodology

• Include the use of racial and socioeconomic 

demographic indicators in all research. 

• Ensure that the social sciences reinforce and

enhance the findings of biomedical science, 

requiring the development of effective scientific

quantitative and social qualitative models, oftentimes targeting entire families and communities. 

• Incorporate cultural sensitivity and flexibility 

into research models and questions.

• Ensure that morbidity and mortality statistical data

be as timely, accessible, and specific as possible. 

• Create one single depository for all statistics that 

is easy to find and is user friendly. Important 

variables to be included are race, ethnicity, age,

socioeconomic status, morbidity, and mortality.

• Use a longitudinal model to investigate the 

problems of children that manifest later in life.

Calcium Intake

• Uncover additional relationships between childhood calcium intake and the development of 

adult osteoporosis.

• Establish the relationship of phosphorus (diet and

regular soda), smoking, pregnancy, and exercise 

to the development of peak bone mass in girls.

• Investigate the best source(s) of calcium.

• Research ethnic differences in lactose intolerance 

and calcium absorption.

• Investigate the relationship between genetics 

and environment in the development of peak 

bone mass.

• Study the benefit of childhood mineral supplementation.

• Examine the relationship and effectiveness 

of vitamin D receptor sites to peak bone 

mass formation.

• Explore the societal pressures that discourage 

girls from drinking milk (e.g., dieting).

• Establish a working group on bone and musculoskeletal disorders to continue exploration 

of the above research questions.

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Diet and Physical Activity

• Measure poverty and its relationship to healthy

behavior; for example, when a family cannot 

afford fresh food or has no access to organized

sports or accessible playground facilities. 

• Measure available income and recognize the 

family member in control of total family income; 

for example, studies in developing countries 

have shown that children fare better when the

mother has control over family spending.

• Investigate the interrelationship between 

menarche, self esteem, and decreased 

physical activity.

Tobacco, Alcohol, and Other Drug Abuse

• Conduct further research exploring withingroup variations in the substance use of 

various ethnic groups.

• Devise effective prevention interventions 

for these abuses.

• Refine effective prevention and treatment 

strategies, as new information is generated, 

for tobacco, alcohol, and drug abuse.

Childhood Maltreatment

• Study all forms of abuse in the context of the

social, cultural, and economic environment 

in which they occur.

• Assess abuse for a generational and cultural 

component.

• Explore ethnic and cultural definitions of 

child maltreatment.

• Examine the relationship of child maltreatment 

to the development of adolescent- or adult-onset

mental illness.

• Review lifelong effects, both physical and psychological, of underreported incidence of all types 

of childhood maltreatment.

• Develop instruments and techniques to obtain

accurate statistical data.

• Examine the relationship of child maltreatment to

later development of learning disabilities, failure 

to thrive, and drug use.

• Develop instruments that measure both prevalence

and effects of child maltreatment.

• Measure the relationship between child sexual

abuse and early consensual sexual relations, 

pregnancies, and substance abuse.

• Continue multidisciplinary, multiagency 

collaborative efforts such as the effort between

NICHD, NIMH, and OBSSR that investigates 

precursors to abuse.

Normal Growth and Development

• Develop a greater understanding of normal 

physical and behavioral development, including

knowledge of the pharmacologic differences

between males and females and among different age and ethnic groups of children.

• Investigate why certain diseases and conditions 

are more common in female infants and children 

and among certain ethnic groups.

• Examine how the catchup growth lag differs 

based on gender.

• Study how cell growth and differentiation 

are different between sexes.

• Investigate why girls injure differently than 

boys during exercise.

• Conduct research on the critical periods of development in organ systems, particularly the brain.
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• Explore how the lack of a nurturing environment

affects emotional resilience.

• Examine how the impact of the psychosocial 

environment of female children impacts nervous 

system development in childhood.

• Investigate how the physiology of the brain 

differs between girls and boys.

• Study the biochemical markers in childhood 

of chronic disease in later life.

• Understand how molecular biology can be used 

to identify and understand the influence of human

genes on childhood development, diseases, disorders, and conditions.

• Explore how research can best make use of 

the human genome to improve child health.

• Investigate whether the most commonly used 

children’s drugs are equally efficacious and safe 

in children of different ages, genders, and races.

Interaction Between Girls and Their Parents

• Investigate the impact on children who come 

home from school without the benefit of parental 

or other adult supervision.

• Study the effect of maternal depression on 

girl children.

• Examine how decisionmaking authority differs

among ethnic, racial, social, and economic 

groups, in order to target specific interventions.

• Establish the correlation between quality of the

parental relationship and learning disabilities,

neglect, failure to thrive, and drug use.

Hormonal Influences

• Examine the relationship of testosterone to 

male aggression and how it can ultimately 

lead to abuse of females.

• Investigate the effect of cerebral serotonin 

levels and serotonin receptors on depression 

and suicidal behaviors and ideations.

• Study the effect of cerebral serotonin levels 

and serotonin receptors on impulse control 

and thrill-seeking behaviors.

• Conduct research on the effect of estrogen and 

exercise on development of peak bone mass.

• Research the relationship of unopposed progesterone to halted bone density development.

• Explore the reason girls of short stature receive

clinical diagnosis and treatment less frequently

than boys with the same diagnosis.

Environment

• Study the influence of livestock hormonal 

supplementation on children’s conditions.

• Examine the environmental influence of schools,

where children spend much of their day.

• Research the impact of infectious agents by 

age and gender.

Asthma

• Study asthma in relation to the child’s age 

and onset of disease.

• Examine the relationship, if any, between the 

menstrual cycle and exacerbations of disease.

• Investigate the relationships between environmental toxins, air, genetic predisposition, carpet,

mold, cockroaches, and schools to the development of disease and exacerbations of asthma.

Mental Health and Depression

• Investigate whether drugs that are not approved 

for pediatric use (e.g., Zoloft and Prozac) are safe

for use in children.
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• Study whether depression in children is actually

increasing and, if so, why.

• Uncover the relationship between female 

self esteem and drug use, eating disorders, 

and early sexual activity.

• Determine the source(s) of resilience 

in children.

• Investigate the incidence of mental 

health problems in children.

Oral Health

• Initiate a study to develop interventions 

that are effective in eliciting donning of 

protective head gear in females.

• Institute a study that addresses the effect 

of dental anomalies on growth and development, nutritional consumption, enamel 

dysplasia, and self esteem.
Adolescent Years

The specific focus of this working group was 

to explore the differences in populations 

(cultural, ethnic, socioeconomic, rural 

and urban, and disabilities) with respect to female 

adolescent health issues. The group acknowledged 

that most of the health problems in this age group 

are behavioral and community based.

RESEARCH 

RECOMMENDATIONS

• Study normal growth and development for the

diversity within the adolescent female population,

studied at physiological, psychological, and sociological levels as expressed in the diverse populations. Examples of areas to be studied under this

topic include:

– breast development, hair growth, and development of genitalia;

– race and ethnic differences and an acknowledgment that “average” is not necessarily “normal”;

– effect of sexual abuse on physical and social

development and the impact of assaults on 

normal development;

– onset of menarche and population differences;

– longitudinal work to determine normal growth

and development; and

– normal development of sexual identity from

infancy on and how that plays out in young

females’ lives and sexual orientation.

• Examine health-compromising behaviors, individually and in constellation, including risky sexual

behaviors; drug, alcohol, and tobacco use; and

delinquency and victimization.

• Study risk factors, looking at the causes and 

subsequent consequences, including:

– poverty,

– victimization,

– racism and marginalization,

– school failure,

– disability,

– dietary and physical activity patterns that 

are antecedents of adult disease, and

– childhood behavior problems.

• Focus research on understanding the disorders 

of adolescence: gynecological disorders, including

endometrial and menstrual, and mental disorders,

including depression, anxiety disorders, eating 

disorders, and suicide.

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• Sequence-base, target appropriately, and evaluate

prevention, identification, and treatment, including research on:

– physical and sexual assault prevention,

– new treatment modalities and prophylaxis 

for STDs,

– oral one-dose treatments,

– oral-administered partner treatments,

– science-based, female-adolescent-specific

research targeted appropriately, and

– longitudinal studies to evaluate longterm impact.
Reproductive and

Middle Years

More research is needed in many areas for

women in their reproductive and middle

years, including contraception, infertility,

osteoporosis, chronic pain, and cancer. Investigations

need to examine the effects of ethnicity, culture, sexual

orientation, socioeconomic status, and disability on 

the health of women.

RESEARCH 

RECOMMENDATIONS

Women of Color

• Access and screening — Study the impact of managed care on health outcomes of different subgroup

populations. Determine why health care delivery

systems make reproductive health care increasingly

inaccessible to racial and ethnic minorities and

rural women.

• Fitness and health — Identify the mechanisms and

etiological factors for obesity impacting chronic

diseases, with particular attention to exercise, 

prevention of cardiovascular disease, and prevention of diabetes. 

• Contraception – Research development of effective, culturally sensitive prevention interventions 

for different populations and culturally appropriate modifications of safe-sex messages for 

different populations. 

• Infertility – Identify the relationships between 

environmental factors and infertility among 

women of color who are differentially exposed 

to greater levels of environmental toxins than 

Caucasian populations.

• Birth outcomes — Discover a possible connection

between a pregnant woman’s diet and fetal loss

and, if this connection exists, determine if this connection is similar in all racial and ethnic groups.

• Low birthweight — Increase research on explanatory

factors for low birthweight, such as obesity and

insulin resistance.

• Infant mortality rates — Identify the cultural factors

that are predictors of low infant mortality rates

among different populations and how this can 

be transferred to other populations. 

• Premature labor — Investigate its prevention rates

and identified causes in different populations.

• Infectious diseases and STDs — On different ethnic

populations with HIV, full-blown AIDS, and STDs,

augment research to determine how the symptoms

manifest and responses to treatment. More research

is needed especially for populations of women

expected to be at low risk for AIDS.

• PMS — Examine the family history of depression

and the cultural aspects of PMS and their impact

on different populations.

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• Substance abuse — Study antecedents, risk, and

protective factors for substance abuse; trauma for

different ethnic and racial groups; and the resulting consequences of substance abuse. Study the

linkages between substance abuse, mental health,

and co-morbidity and trauma and how these are

culturally mediated. 

• Osteoporosis — Research the prevalence, bone loss

from age 25, and techniques for enhancing bone

mass among different ethnic and racial groups.

• Mental health — Study the efficacy of traditional

approaches to mental illnesses, including alternative treatment interventions that work for certain

populations. More research is needed on mental

health for other groups as well as their responses 

to different treatment modalities.

• Study pharmacodynamics, drug efficacy, and side

effects for different populations of women.

• Investigate postpartum depression among different

racial and ethnic groups. 

• Cancers — Research the relationships between

nutrition and chronic disease. 

• Violence — Identify and define abuse (physical, 

verbal, and sexual) among different racial and 

ethnic populations and how specific cultures 

contribute to abuse. 

• Endometriosis, fibroids, and hysterectomies — 

Conduct new research on the causes and prevalence of endometriosis and fibroids in these 

populations. Explore racial differences in efficacies of alternative treatments.

• Chronic pain — Identify the major reasons for

chronic pain among different ethnic groups. 

Poverty and Urban Health

• Develop and test measures of social class, for clinical and population-based health research, that are

most reliable and valid for populations of women

that differ by race and ethnicity, sexual orientation

(or type of partnership), and age — at individual,

household, and neighborhood levels.

• Describe social class heterogeneity in patterns of

risk, disease, health, and mortality within racial

and ethnic groups by gender.

• Investigate the interrelationship of social class and

race and ethnicity for different types of cancers to

determine why the gender-cancer relationship is

direct for some cancers and inverse for others.

• Determine how the lifetime trajectory of social class

and socioeconomic position affect health, disease,

and mortality among women, and whether there

are age, period, and cohort differences.

• Investigate how the interplay of genetic and environmental (including socioeconomic) factors affect

women’s health during the reproductive years.

• Evaluate to what extent migration and generation

in the United States confer a protective effect on

women, independent of socioeconomic position.

Women with Disabilities

• Body image — Determine the impact of acquired 

or continuing disability on body image and self

esteem, and which interventions will prevent 

social isolation and withdrawal from healthmaintenance activities.

• Lesbians with disabilities — Document the health

care experiences of lesbians with disabilities. Eliminate heterosexual presumptions from medical

history-taking and research instruments. Provide

funding to develop relevant educational materials

that address specific health issues of lesbians 

with disabilities.
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• Contraception — Evaluate the choices of contraceptions for immobilized patients (ruling out

thrombotic risk) and women with MS, lupus, 

cardiovascular conditions, and stroke. Investigate

adverse reactions of conventional contraceptive

options for women with disabilities and develop

possible interventions to make these options safer.

• Urinary tract infections (UTIs) — Conduct research 

on interventions to prevent recurrent UTIs in

women with neurologic dysfunction, on low-dose 

prophylaxis, on anticholinergics, and on diet 

modification. Prevent UTIs in women who use

catheters, such as women with spinal cord injury 

and spina bifida.

• Infections (STDs) — Research prevalence of 

chlamydia and gonorrhea (and undiagnosed 

sequelae), concentrating on altered manifestations in sensory-impaired women.

• HIV — Investigate the prevalence of HIV in 

women with disabilities and whether manifestations are different in women with disabilities.

• Pregnancy — Investigate prenatal and pregnancyrelated issues for women with disabilities:

– How disability interacts with pregnancy;

– Mobility adjustments related to pregnancy;

– The pressure points with wheelchairs;

– Whether bladder dysfunction is exacerbated 

by pregnancy;

– Ways to manage pyelonephritis;

– Alternative monitoring for contractions in

women with sensory impairment — the 

effectiveness of home uterine monitoring;

– How the induction of labor affects neurologic conditions;

– Appropriate anesthetic agents for women 

with STI, MS, and CP — whether an epidural has lasting neurologic consequences;

– Increased risk of C-section — whether there 

is a true need for it or whether a C-section 

is performed because of the doctor’s anxiety;

– Management of autonomic dysreflexia — how

soon to intervene and what parameters to use;

– How women with disabilities prepare for 

parenting;

– What adaptive strategies and techniques are 

successful and what adaptive equipment 

(disability-specific) is useful; and

– How mothers with disabilities adjust to the 

transition from pregnancy to postpartum — 

weight changes, independence issues, need 

for additional assistance, and incidence of 

postpartum depression.

• Fitness and health:

– Target research at the long-term benefits 

of exercise for women with disabilities.

– Explore the effects of exercise and fitness 

on secondary conditions, including prevention and intervention.

– Conduct further research regarding the 

impact of exercise by severity of disability.

– Research the attitudes of women with disabilities toward participation in physical 

activity, and the attitudes of individuals 

who provide services to them.

– Study and overcome the barriers to adequate

nutrition for women with disabilities.

– Promote better weight management for 

women with disabilities.
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– Determine ways to help women with 

disabilities manage stress.

• Secondary conditions — Target research at basic 

epidemiology of secondary conditions. Develop

multifaceted interventions to prevent secondary

conditions, considering the regular monitoring 

of women’s health status and the availability 

of appropriate assistive technology and community support.

• Bowel and bladder management — Research 

new technology, external collection devices, 

biomaterials for bladder and sphincter reconstruction, physiological consequences of disability, pelvic floor muscles, changes over long 

time periods, bowel irritation, stretching of 

the urethra, and renal stones.

• Violence — Investigate the incidence and prevalence of abuse among women with disabilities.

Identify risk factors that contribute to violence 

and abuse against women with disabilities and

develop effective interventions to reduce the 

risk of abuse. Train health care providers to 

recognize the signs of abuse among women 

with disabilities.

• Substance use and abuse — Determine the 

interaction between substances such as 

tobacco, alcohol, and other drugs, and 

various disabilities. Develop methods to 

prevent and treat substance abuse among 

women with disabilities.

Pharmacokinetics

• Support studies on the bioavailability and drug

delivery from a social and biophysical point of

view for various racial and ethnic groups.

• Among women of different populations, study 

the pharmacokinetics and pharmacodynamics 

of folic acid for the prevention of neural tube 

birth defects.
Perimenopausal Years

The menopausal transition is one of the unique

aspects of a woman’s middle years. However,

there is a lack of knowledge about the fundamental biologic processes involved in menopause.

More research is also needed on the perimenopausal

experiences of women from differing socioeconomic,

ethnic, sexual orientation, and disability groups.

RESEARCH 

RECOMMENDATIONS

• Investigate lifelong developmental and contextual

influences on the perimenopausal transition,

including physiological (e.g., endocrine, immune,

genetics), socioeconomic, cultural, ethnic, and

lifestyle (e.g., diet, activity) dimensions.

• Study basic biological processes across the

menopausal transition.

• Investigate experiences of symptoms such 

as hot flashes and bleeding and how women 

make meaning of them as a basis for self care 

or seeking health care.

• Examine mental health problems (especially

depression) that can appear or continue into 

this period and the biological impact of the

menopausal transition on mental health.

• Study relationships between cognition, emotion, and immune response (psychoneuroimmunology) during the menopausal transition 

as a basis for understanding how culture, 

lifestyle, and behavior affect immune response 

and chronic health problems.

• Investigate fertility management spanning 

pregnancy prevention, pregnancy care, 

and fertility enhancement.

• Explore the life cycle course of health behaviors,

such as nutritional intake and exercise patterns,

and cumulative environmental exposures, including workplace exposures as they are modified by

pregnancy, birth, breastfeeding, and menopause.

• Examine environmental exposures, such as

endocrine disrupters and workplace stress, 

and their consequences for midlife health.

• Conduct research on genetics and specific 

health problems such as cancers (particularly 

breast cancer).

• Explore midlife women’s experiences of 

HIV/AIDS and the menopausal transition.

• Study midlife women’s experiences of violence 

and models of violence prevention.

• Investigate health care needs of special 

populations within this transitional period.

• Enhance information dissemination and 

exchange for consumers and providers 

through the following efforts:

– Identify information appropriate for 

special populations.

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• Study the effects of health care delivery system

models that will encompass:

– training of health professionals,

– time spent with patients,

– provider-patient interactions, and

– women’s access to health care and 

specific services as these are each 

linked to health outcomes.

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– Promote understanding of the relationship

between women and their health care providers and factors that enhance trust.

– Develop a clearinghouse on perimenopausal

issues that will include evaluation of information through mechanisms such as those used 

for evidence-based practice and the U.S. 

Preventative Services Task Force.

– Investigate informed consent and ethics 

related to the conduct of research with different ethnic and socioeconomic groups.

– Study patient-provider communication 

patterns and effects on health outcomes.

– Advance understanding of the therapeutic 

interventions available to women during 

the perimenopausal period including:

• use of allopathic and alternative and 

complementary medicine and their 

relationship to primary, secondary, and 

tertiary prevention (e.g., spirituality, 

vitamin therapy, alternate care providers);

• use of hormone therapies and interactions with genetics, other systemic 

conditions, environmental factors, and 

alternative therapies;

• patterns of use of hormones and alternative therapies in special populations

including their use by women with

HIV/AIDS; and

• understanding of therapies such as SSRIs 

and evaluation of them with respect to 

outcomes such as leaving violent relationships and changes in socioeconomic status.
Postmenopausal Years

As the population of older women continues 

to grow, it becomes increasingly important 

to expand the existing scientific knowledge

base so that effective strategies can be developed to

optimize the health status of postmenopausal women. 

RESEARCH 

RECOMMENDATIONS

Health Status of Special Populations of 

Postmenopausal Women

• Examine descriptive epidemiology on occurrence 

of risk factors and diseases in postmenopausal

women of special populations.

• Define characteristics that influence health status

and behaviors to reflect the heterogeneity of 

special populations.

• Inspect the health outcome differences in racial

subgroups of postmenopausal women.

• Explore the impact of survivorship of chronic 

disease on quality of life as perceived through 

the special population individual’s perspective 

in terms of the physical, emotional, social, and 

economic changes they experience.

Behavior and Health in Special Populations of 

Postmenopausal Women

• Investigate the effect of accumulated risks on 

specific health problems and special populations 

of postmenopausal women.

• Examine the influence of living in Western 

societies on the increased rate of breast cancer 

in Asian women in the United States.

• Investigate the health of women with disabilities 

in the postmenopausal years, including facilitators

and barriers to their optimal health.

• Study the scientific evidence for the role of

menopause versus aging in conditions common 

in postmenopausal years and chronic diseases.

• Investigate differences between postmenopausal

women and men in response to surgical and 

pharmacological treatment interventions.

• Identify differential risk factors for stroke in 

postmenopausal women and men and in subpopulations of women.

• Examine possible explanations for the differing

prevalence of diabetes among subpopulations 

of postmenopausal women.

• Explore how to improve rates of regular mammography, clinical breast exams, and colon cancer

screening, focusing on minority and underserved

postmenopausal women through the use of innovative, culturally appropriate strategies.

• Address ways of improving compliance with 

followup and treatment recommendations following abnormal diagnostic and screening tests in

postmenopausal women, including the examination of psychological effects of positive testing.

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• Examine the actions of all natural hormones 

(e.g., DHEA, natural estrogens, melatonin, human

growth hormone, natural progesterone, thyroid

hormones) in postmenopausal women.

• Compare the effectiveness of different estrogen

treatments in postmenopausal women of different subpopulations.

• Explore pharmacologic differences in drug 

outcomes and drug-drug interactions specific 

to postmenopausal women.

• Investigate the reasons for drug use and misuse

among postmenopausal women of special 

populations.

• Delineate mechanisms underlying postmenopausal women’s and men’s differential sensitivity

and responsivity to pain threshold and tolerance

measures. Validate measures of pain in subpopulations of postmenopausal women, informed by

specific cultural beliefs and practices.

• Explore possible explanations for gender and 

age differences in mental health effects.

• Identify the effects of racism on the health of 

postmenopausal women in special populations.

• Explore the mental and physical issues specific 

to postmenopausal lesbian women.

Environmental Exposures and Health in Special 

Populations of Postmenopausal Women

• Explore the effect of environmental toxins on 

postmenopausal health.

• Examine the effects of the workplace on postmenopausal low-income service workers (e.g.,

women who clean offices and hotels).

• Investigate the effects of pesticides on postmenopausal migrant workers.

• Explore the nature and outcomes for postmenopausal women of stressors associated 

with military life.

• Examine how the stress of war affects postmenopausal women in comparison to men and what 

interventions, if any, exist to lessen these effects.

Health Provider and Researcher Interactions with 

Special Populations of Postmenopausal Women

• Train health care providers to consider postmenopausal women of different subpopulations 

in terms of their entire needs — emotional, 

rehabilitation, social, and financial — when 

treating illnesses.

• Investigate how to improve health provider and

researcher sensitivity, such as how questions are

asked and body language.

• Determine the most effective mixture of health care

provider types for delivering health care to special

subpopulations of postmenopausal women.

Research Methods in Special Populations of 

Postmenopausal Women

• Address the role of incentives for recruitment and

retention of special populations of postmenopausal

women in studies and to provide allowances for

funds in clinical trials for recruitment and retention of participants. 

• Coordinate research activities with community 

hospitals, clinics, and reservations so that postmenopausal special population women can 

access them.

• Construct new strategies for instrumentation 

reliability and validity for postmenopausal 

special populations (e.g., translation issues).
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• Increase the use of behavioral research and 

strategies to accompany medical diagnosis and 

treatment procedures for special populations 

of postmenopausal women.

• Fund additional longitudinal studies for special

populations of postmenopausal women.

• Establish a clearinghouse for rapid dissemination 

of research findings to researchers, health care

providers, and the public, and an inventory and 

distribution center for intervention materials 

that have been proven effective.

Elderly and Frail

Elderly Years

I

n considering the health of older women, 

the World Health Organization concept of 

health applies: all aspects of women’s physical,

social and behavioral, and environmental health are

important. Across the diverse and growing populations

of older women in the United States, there is a need 

for adequate access to and coordination of a wide 

range of health care providers and care givers.

RESEARCH 

RECOMMENDATIONS

Biological and Physiological

• Determine the effects of chronic illness and disability, such as AD and other dementias, cancer,

and osteoporosis, on the quality of life for older

women and frail elderly women.

• Conduct research that results in applications on 

the biomechanics of older and frail elderly women.

• Continue research on the longitudinal, multigenerational effects of DES.

• Examine drug action and effects in relation 

to age, racial and ethnic groups, and gender.

• Study multiple drug, drug-food, alcohol, 

tobacco, and other interactions.

• Study the impact of natural and synthetic 

estrogens on different physiological systems,

including the immune, endocrine, and cardiovascular systems, and on cognitive and affective

processes and on sleep.

• Investigate the impact of oral health on quality 

of life and the general health of aging women, 

as well as on specific diseases.

• Conduct research studies on less well-known 

physiologic conditions in elderly women (e.g.,

angiodysplasia of colon, vertigo, hiatal hernia).

• Support scientific studies to evaluate the effectiveness, benefits, risks, and costs of alternative and

complementary medicine.

• Study the shift from subclinical to clinical conditions in older and frail elderly women.

• Study multisensory impairment in older women.

• Produce a better understanding of the physiological aging processes across racial and ethnic

groups of women.

Psychosocial

• Study the relationship between self efficacy and 

positive self image and outcomes such as functional independence and self care as mediated 

by family and social supports.

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• Examine the concepts of health (body image),

aging, disease, and disability (and causes and 

consequences of each) as a function of age, 

knowledge and attitudes about aging, ethnicity, and cultural background.

• Address gaps in information between the end 

of the working years and the transition to the 

need for assistance and nursing care.

• Identify the developmental course of aging and

functional levels, to allow older people and care

givers to know what to expect.

• Study the role of multisensory impairment on 

personal and social functioning of older women.

• Investigate the living environments — including

physical and social parameters — of older women.

• Examine the influences of spirituality on health

outcomes in diverse groups.

• In light of growing evidence, conduct research 

on the causes, consequences, and interventions

related to physical and emotional violence, 

abuse, and traumatic stress in older women.

Health Practices and Interventions

• Study the influence of age, culture, and socioeconomic status on older women’s health 

practices and the receptivity to lifestyle interventions, and the effectiveness of health behavior

interventions in different population groups 

of older women.

• Evaluate elderly and frail elderly women’s use 

of alternative and complementary health care 

services, focusing on self care and health education preventive services.

• Examine health and life choices as they impact 

living arrangements (independent, congregant,

family, or institutional) and health care decisionmaking.

Effects of Interventions

• Regarding health behaviors and lifestyles of 

older and frail elderly women, study the differences in intervention applications for exercise,

smoking cessation, and nutrition.

• Conduct research on the effectiveness of interventions on health conditions and health events 

in the lives of older women and frail elderly

women, particularly in regard to:

– Incontinence,

– Falls,

– Depression and anxiety,

– Cognitive impairment,

– Sleep, and

– Traumatic events such as physical and 

emotional violence.

• Investigate medication use by older and 

frail elderly women, particularly HRT and 

polypharmacy.

• Examine patterns of alcohol and substance abuse 

in the various populations and subpopulations 

and across the sociocultural spectrum.

• Address the cost of intervention choices for 

different populations.

Formal and Informal Caregiving

• Conduct research on formal caregiving that

addresses the following issues:

– Caregiver selection;

– Training and education given to care givers;

– Cultural matching between care giver 

and client;
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– Implications of transition from family to 

paid caregiving, or a mix of both;

– Work conditions that maintain, strengthen, 

or sustain quality caregiving for family care

givers, volunteer care givers, and care givers 

in institutions; and

– Outcomes measurement — training, effectiveness, client satisfaction, and impact of 

caregiving on care givers.

• Conduct research on family caregiving that

addresses the following issues:

– Work conditions that maintain, strengthen, 

or sustain quality caregiving;

– The multiple caregiving roles and how they 

are handled by families;

– Cultural and socioeconomic differences in 

family caregiving;

– Intergenerational relationships and family

dynamics involved in caregiving; and

– Role of older women as care givers.

• Investigate the new models for providing care,

including research on the effectiveness of alternative caregiving arrangements for long-term care —

assisted living options, new ways of providing care

in traditional settings (e.g., special care units), and

the role of volunteerism to reduce the burden of

care givers.

• Understand the factors associated with access 

to care across age, gender, and ethnicity and 

on the levels of functioning.

Provider and Client Interaction

• Investigate gender, ethnic, and regional influences on health care practices of older persons,

especially diagnosis and treatment.

• Examine the interactions among patients and 

care providers, particularly among different 

cultures, ages, SES groups, and defined racial 

and ethnic groups.

• Enhance patient and provider interaction of 

elderly and frail elderly and the relation to 

quality of care, patient and provider satisfaction, 

prescribing patterns, and health outcomes.

• Study characteristics and training of health care

providers who provide service to older people.

• Investigate barriers to the receipt of appropriate

health care by the homebound and disabled, 

and of health care to older women in general.

• Conduct research on informed consent and the

decision process for participation in health care 

or research, to help identify barriers to including

older women in research studies.

• Explore the impact of changing health care 

financing and delivery systems on subgroups 

of older women.

Methodological Issues

• Develop measures for nursing home residents 

that are culturally and ethnically sensitive for 

quality of life, SES differences, and different 

levels of cognitive functioning.

• Include the oldest old and institutionalized 

persons in studies; develop the ability to analyze such data by age and gender. Investigate 

age in terms of younger elderly (65 to 84) and 

older elderly (85+), compare outcomes, and 

differentiate groups by functional status rather 

than by age groups.

• Develop research strategies to recruit old and 

oldest-old women, as well as members of all 

ethnic groups and SES levels, as research participants. Include community organizations 

and their members as partners in research.
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• Determine whether there are circumstances 

in which it is appropriate to consider age vs. 

functional status as a criterion for access to 

care or participation in research.

Death and Dying

• Investigate attitudes toward death as a function 

of ethnicity, culture, and age.

• Examine end-of-life decisions, including 

end-of-life care and cultural and ethnic backgrounds and their influence on such decisions.

• Conduct research on managing death and 

ethnic and cultural differences regarding pain 

management, family support, place of death, 

dignity, special needs of women as informal 

care givers for dying persons, and assisted dying.

• Include quality of dying and ways to improve 

the end of life for patient and care providers.
career issues for women scientists

CAREER ISSUES FOR

WOMEN SCIENTISTS

I

n November 1997, the working group on 

Career Issues for Women Scientists met 

in Bethesda, Maryland, to discuss areas 

of concern and progress and to develop final 

recommendations for ORWH.

Recommendations and Conclusions

The following recommendations apply, 

where appropriate, to the entire educational 

and career path from grammar school up to and 

through medical school and the various health 

science careers. The intent is to include all populations of women, and to foster collaboration 

among external agencies, associations, academic 

institutions, and the Federal Government.

Data Collection

• Create a comprehensive database on women 

scientists by field, a database that should be 

widely available to university and industry 

search committees for new laboratory chiefs, 

division heads, and department chairs.

• Catalog and organize a list of existing databases to include emerging leaders, mentors, 

and special populations of women.

• Identify new database needs.

• Collect outcome data to determine the effectiveness

of specific programs targeted at women scientists.

Program Monitoring for Institutional Accountability

• Evaluate effectiveness of principal investigators 

in supporting academic careers of women and

minority scientists.

• Evaluate effectiveness of institutional programs 

aimed at enhancing careers of women and minorities.

• Collect statistics on gender gap issues such as salary,

tenure, and percentage of women at senior levels.

Dissemination

• Develop mechanisms for disseminating information

and data for those with and without Internet access.

• Assist institutions whose faculty are still unable to

gain Internet access.

• Expand the ORWH web site for disseminating

research information and other data pertaining 

to women scientists.

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• Link the ORWH web site to other databases 

and web sites within NIH and in professional 

societies, biomedical organizations, academic 

institutions, and community groups.

Institutional Responsibility, Collaboration, 

and Partnering

• Encourage each institution to create new programs to address inequities in representation 

and participation of women and minorities 

in science and medicine.

• Include in expectations for NIH-funded principal

investigators the point that training for investigators should include:

– Requirements for special attention to 

recruiting, training, and advancing all 

underrepresented groups in medicine 

and biomedical sciences; and

– Requirements for institutional responses to

harassment and discrimination at all ranks, 

but particularly in training programs.

• Issue a contract from NIH for models of institutional self-study and corrective actions for any

practices that hinder or discourage underrepresented groups from full participation in research 

and training in biomedical research.

• Increase participation of underrepresented groups

at all levels in NIH (e.g., study sections, advisory

groups, conferences). The same point applies to

partnering institutions where appointment to committees, invitations to speak, and travel to conferences all add to the academic maturation of the

faculty member.

Education and Training

• Encourage institutions to increase efforts to introduce science into the education of children from

kindergarten through high school. 

• Encourage NIH to offer competitive funding to

increase the ability of individual institutions to

develop quality programs to attract able young

people into the biomedical sciences.

• Support and expand existing programs that 

encourage the exposure of women and minorities to science and medicine at the precollege 

level in order to increase the pool of student 

applicants from underrepresented groups.

• Expand the NIH Office of Education Scholarship Program for Minority Undergraduates 

with more vigorous outreach.

• Establish partnerships between NIH and academic institutions, industry, or professional 

societies to develop programs for enhancing 

careers of women scientists.

Career Enhancement

• Expand the ORWH re-entry program. Providing opportunities for women who have already

completed their professional training but have

taken time off for family reasons will salvage 

precious talent and encourage women to 

resume careers in science.

Ethnicity of Female Faculty in U.S. Medical Schools

Source: American Association of Medical Colleges (AAMC) Faculty Roster System. Bickel J,

Croft K, Johnson D, and Marshall R. Women in U.S. Academic Medicine Statistics 1997,

Washington, D.C.: AAMC, 1997. Used with permission.

Non-White (4,014) Total (22,779)

Asian (2,272) 10%

Black (938) 4.1%

Mexican American (108) .5%

American Indian (30) .1%

Other Hispanic (427) 1.9%

Puerto Rican (239) 1%

Non-White

(4,014)

17.6%

White

(17,299)

75.9%

Unknown

Ethnicity

(1,466)

6.4%
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• Develop and fund a national fellowship program 

to support protected time for academic activities 

of women junior faculty at those points in their

careers when they must teach, conduct research,

compete for grants, publish, and practice (if a clinical faculty member) at the same time they are

assuming increased family or other responsibilities.

Such a program would be particularly valuable 

for women in science and medicine, but could 

be made available to men junior faculty if they 

face similar obstacles.

• Establish collaborative programs with the U.S.

Department of Education and Department of 

Rehabilitative Services.

Leadership Training

• ORWH should support appropriate professional

societies and academic institutions in their development of programs to enhance management 

and leadership skills in women scientists.

Professional Visibility of Women

• Encourage NIH to increase the participation of

women and minorities at all levels of NIH (e.g.,

study sections, advisory groups, conferences). 

• Encourage academic institutions to place more

women on appointment and promotion committees as well as tenure committees. Ensure that

women have visible teaching roles (e.g., lectures,

grand rounds presentations).

• Encourage journals to include more women 

on their editorial boards.

Mentoring

• Define, facilitate, and reward mentoring.

• Require the principal investigator of every funded

RO1 grant to make a commitment to mentoring 

of junior faculty included in the grant.

• Incorporate into the criteria of judging applications

for grants and contracts a component of mentoring

and outreach. 

• Encourage collaboration among NIH, academic institutions, and professional societies to develop programs for training mentors (with NIH support) and

to adopt the most successful models of mentoring. 

• Encourage NIH to include in its own workshops 

a session that focuses on development of mentoring skills. 

Cultural Issues and Social Norms

• Fund a study of the cultural and sociologic aspects

of being a woman in biomedical science careers 

to see how these beliefs impact on the success 

of a woman’s career.

• Study the different definitions men and women

may use to describe work.

• Encourage NIH and other institutions to recognize legitimacy of different work styles, if the 

output is identical.

“It is our view that it is unconscionable to allow

talented women (and men) to wither on the academic

vine when a modest amount of support could maintain

their academic careers and preserve their capacity to

contribute to the research and teaching that are

absolutely vital to the future of medicine.”

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

Harvard Medical School
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• Develop a survey to document the work styles 

of men and women and analyze for correlations

with advancement in biomedical careers (hours 

at work vs. productivity).

• Introduce educational programs to educate 

the scientific community about harassment 

and discrimination as it affects all women and 

minority scientists, but particularly trainees.

• Encourage NIH to convene a conference to 

study how social norms impede the careers of

women scientists. This conference would focus 

on factors that discourage entry or retention 

of women at all levels in biomedical careers.

• Incorporate enough flexibility in NIH grants 

to accommodate the transient but compelling

needs of women around issues of childbearing.
selected issues in research design

HEALTH OF SPECIAL 

POPULATIONS 

OF WOMEN

S pecial populations” includes, among others,

women of different racial, ethnic, and cultural

origins; women with disabilities; lesbians; women

living in urban and rural settings; and immigrants.

Any one of several data books demonstrates differences in health status and health outcomes among

different populations of women. For example, whereas

heart disease and cancer are the leading causes of death

for all American women, cancer is the leading cause of

death for Asian women. Cerebrovascular disease is the

third leading cause of death for Caucasian, AfricanAmerican, Asian, and Hispanic women; for American

Indian women, however, the third leading cause is 

accidents and unintentional injuries. Death rates from

cancer vary among the different populations. For 

example, the death rate from breast cancer reported 

for African-American women is 31 per 100,000,

whereas American Indian women in New Mexico 

are reported to have the lowest incidence with a 

death rate of 9 per 100,000.

Interpretation of the data from the source books

and from epidemiologic and other types of research

requires an understanding of how special populations

are defined. Agreement is needed among researchers on 

a uniform method, so that sound comparisons can be

made. Differences in health status and health outcomes

among the different populations are known to correlate

with educational, cultural, and behavioral variables;

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“

Detailed Race and Hispanic Origin of U.S. Women, 1980 and 1990-1993, Numbers in Thousands

RACE/ORIGIN 1980 1990 1991 1992 1993

All Persons 226,546 248,710 252,177 255,078 257,783

Women

White 99,835 106,561 107,631 108,584 109,515

Black 14,046 16,063 16,412 16,653 16,925

American Indian and Alaskan Native 718 1,041 1,068 1,081 1,099

Asian and Pacific Islander 1,915 3,805 4,087 4,279 4,444

Hispanic 7,329 10,966 11,460 11,871 12,405

Source: National Center for Health Statistics: Health, United States, 1995.
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individual preference; availability of services; differences in treatment of disease; and differences in 

supplementary services. However, physiologic and

pharmacokinetic differences and predisposition to 

certain disorders may explain some of the differences as well.

Cultural and Behavioral Differences

The roles of traditional cultural values and 

sociologic and behavioral factors in health maintenance must be recognized. 

Provider Attitude Differences

One cannot examine differences in health 

outcomes among special populations of women 

without addressing physician attitudes and practice. Cultural insensitivity of providers has been 

implicated as a reason that women of color fail to

receive health-promoting care. Attitudinal barriers

toward individuals with disabilities remain. Differing practice patterns may relate to patients’ race. 

“. . . my life as a disabled woman will shed some

light on this important topic. . . I continue to forge

ahead and tackle each day’s challenges and obstacles

head on. Yes, there will be detours along the way. 

That is a given circumstance and also my challenge.”

Mary Hepburn
SEX AND GENDER 

DIFFERENCES IN 

CLINICAL STUDIES

Designing Clinical Studies

That women and minorities should be 

“included” suggests that it is appropriate 

to design a study with men as the major 

focus as long as women are included. This concept

should be addressed more clearly to promote studies

that are initially designed for women or minorities. 

The point is not just to increase the number of women

in clinical trials, or even how to determine if women

are eligible for trials; rather, the point is what is being

studied, the nature of how the experimental groups 

are being determined, and how drugs and devices 

are being tested. There is a lack of studies on healthy

people, an area for which research designs must 

be unique to healthy women.

Balancing Research Cost While Asking Clinically 

Significant Questions

Adding sex and gender issues to a biomedical

study can considerably increase study costs, at a time

when pharmaceutical companies and grant agencies 

are cutting costs. Excluding women from trials would

result in inadequate data, which could lead to inappropriate treatment, added risks for women, and increased

costs to society. The medical research community is

currently examining the role of managed care organizations (MCOs) in women’s health research. Because large

numbers of people use the services of MCOs, an extensive pool of data is potentially available to researchers.

Recruiting and Retaining Women in Clinical Trials

Unless the appropriate women, in sufficient numbers, participate in clinical trials, the base of biomedical

knowledge about specific conditions and diseases will

always have major gaps. Designing research models to

include women in clinical studies presents new questions about how to recruit women. The recruitment

techniques that are used for men may not be effective

for women. Informing the appropriate people is key 

to recruiting for clinical trials; once informed about a

study, whether a woman decides to participate may

depend on attitudes toward the medical profession,

research team members, and clinical studies in general.

Ethical and Liability Considerations

A major ethical and liability consideration is the

inclusion of women of childbearing age in clinical 

trials. It should be noted that excluding women does 

not exempt manufacturers from liability risks; the 

manufacturers are still responsible for knowing how

pharmaceutical agents affect women. Although pregnant women have been excluded from clinical trials 

in the past, they do use drugs during pregnancy. 

Sex and Gender Differences

Women and men are obviously different in 

regard to the presence of hormones. It is vital that

investigators determine under what conditions sex 

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and gender differences manifest and design clinical 

studies appropriately to examine these situations.

Women and men also differ biologically in body 

composition, size, and metabolism. The design of 

diagnostic technology and medical devices poses 

concerns. Research on the aging process should 

include women; on average, women live 7 years 

longer than men and constitute the majority of 

the population over 65.

Longitudinal and Life Phase Research

Because of the unique role that female hormones

play in women’s lives, women go through various

stages based on hormone support. It is essential to 

conduct studies that include and describe the different phases of a woman’s life, and to classify women 

by the menopausal stage, instead of by age only.

Research designs and study instruments should be

developed that describe the menstrual cycle longitudinally and assess hormone differences across 

menstrual cycles. 
RACIAL, ETHNIC, AND

CULTURAL DIVERSITY

To a large extent, a woman’s health status 

may depend on the group or subgroup to

which she belongs. Despite statistics that

clearly indicate the disparities in health status among

various subpopulations of women, clinical research 

that has included women at all has focused on Caucasian, middle-class, heterosexual, able-bodied women.

The percentage of minority groups in the population 

is increasing and the disparity between the health 

status of the majority group and that of minority

groups is widening.

Recommendations

The working group on racial, ethnic, and cultural

diversity recommended the following ways in which

NIH can more effectively involve and benefit diverse

communities of women in research projects:

• Give peer review groups strict criteria to follow 

in reviewing grant applications and proposals,

specifying requirements as to gender, race, and 

ethnicity of study participants.

• Diversify peer review groups, ensuring that they

include women and minorities.

• Encourage collaborative research with minority

institutions, states, and communities.

• Award more grants to minority women 

investigators.

• Examine the cultural and financial barriers to 

the participation of low-income populations 

in research.

• Increase the number of supplemental awards 

to minority students.

• Meet with journal editors to encourage them 

to require that clinical studies report data 

classified by race and ethnicity.

• Encourage researchers to publish their experiences, successful and unsuccessful, in working 

with minority populations.

• Establish a clearinghouse for the publication of

research experiences with minority populations.

• Relax guidelines for inclusion in studies so that

potential participants are not excluded from studies

because they have some disease or condition that

makes them ineligible to participate. 

• Encourage a more comprehensive approach to 

the study of health problems of minority women

than the traditional medical model allows.

• Encourage the development of research models 

that study population assets and resiliencies 

that prevent disease and promote survival.

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The working group also recommended the 

following ways in which investigators can more 

effectively involve and benefit diverse communities 

of women in research projects:

• Report data by gender and racial and ethnic 

categories.

• Analyze the data for previously published studies 

by gender, race, and ethnicity, and publish an

addendum to the studies.

• Report experiences, successful and unsuccessful,

working with participants from diverse racial, 

ethnic, and cultural groups.

• Design more studies that are homogeneous in

terms of ethnic and racial groups in order to 

find out more about a particular group.

• Collaborate on research projects with researchers

who have access to other populations, using the

same variables. 

• Examine substance abuse and violence in the 

general population, not only in low-income 

populations.

• Design more studies to include two groups of

women who are now usually excluded from clinical studies: women with disabilities and lesbians.

• Ask women within the community to collaborate 

on projects by helping to identify the problem to 

be studied, suggesting appropriate recruitment

strategies and methods of data collection, and 

participating in the analysis and interpretation 

of study results.

• Include the participants’ families in subgroups

where family is of great importance.

• Collaborate with community and church groups 

in planning, conducting, and evaluating research.

• Collaborate with churches on research in 

minority communities.

• Reach out to those minority women who never

enter the health care system or who do so only 

at a time of crisis.

• Develop culturally appropriate instrumentation 

and outcome measures.

• Determine what participants themselves want 

to achieve through participation in the study.

• Examine barriers to health care from the participant’s point of view, which may differ radically from

the researcher’s preconceptions of the barriers.

• Use a qualitative rather than quantitative model 

of health care so that researchers can understand

the health care needs of the community and how

well they are meeting those needs.

• Establish community-based centers for research,

much like the community centers that have been

established for HIV and drug abuse.

• Find ways to give back to the community through

providing health care, education and training, 

and employment.
MULTIDISCIPLINARY 

PERSPECTIVES

Research on women’s health provides 

a unique opportunity to assemble 

researchers from multiple disciplines. 

Collaborative research projects on women’s 

health can cut across disciplinary boundaries 

within the basic and molecular sciences, within 

medicine, and with other disciplines including, 

but not limited to, nursing, pharmacy, anthropology, psychology, sociology, health education, social

work, economics, and demography. Multidisciplinary research should not replace single-discipline

research but should supplement it, thereby 

enriching understanding and permitting the 

development of broad-based knowledge.

The working group specifically makes the 

following recommendations to encourage multidisciplinary research on women’s health.

• Encourage multidisciplinary research by 

appropriately structuring NIH funding.

– Identify multi-institute issues.

– Encourage inter- and intra-institute multidisciplinary research.

– Use RFA and RFP mechanisms to support 

multidisciplinary research.

– Establish ORWH as a broker.

– Encourage multidisciplinary research through

ORWH funding priorities.

– Establish multidisciplinary coordinating groups.

– Convene multidisciplinary conferences.

– Create core centers to encourage close cooperation, communication, and collaboration

among investigators with similar interests.

• Reward multidisciplinary research within 

academic institutions.

– Increase the amount of multidisciplinary

research conducted on women’s health issues 

by increasing collaboration between NIH 

and academic institutions.

– Encourage promotion criteria that stimulate

multidisciplinary research.

– Encourage scientists to learn how to “package”

multidisciplinary careers.

– Encourage NIH funding mechanisms that 

support multidisciplinary research and 

training at academic institutions.

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• Provide researchers with training in multidisciplinary research.

– Establish multidisciplinary training programs.

– Publicize effective individual and institutional 

role models.

– Publish and publicize the process of putting

together multidisciplinary teams.

– Recognize mentors.

– Encourage and provide funding mechanisms 

for continuing education in fields other than

one’s area of primary expertise.

– Encourage NIH institutes to fund multidisciplinary training.

– Develop inter-institute review processes 

and funding for training awards.

• Multidisciplinary research proposals are often

reviewed by single-discipline individuals.

– Expand the use of ad hoc reviewers on 

standing committees.

– Use ad hoc review committees.

– Solicit reviewers with appropriate multidisciplinary expertise.

– Inform applicants how to use existing 

review structures.

– Identify and publicize successful models.
selected topics in Health Impact and HEALTH OUTCOMES

Selected Topics in

Health Impact And

Health Outcomes

These selected topics in health impact and

health outcomes were presented at the

Philadelphia regional meeting and the 

Bethesda national meeting of the Beyond Hunt Valley

activities to update the agenda for women’s health

research for the 21st century. Because of the extent of

work required, it may be necessary to pool resources 

of both public and private sectors. Within the public

sector arena, broad interagency collaboration (NIH,

FDA, AHCPR, NSF, and CDC) is crucial to develop 

and implement methodical and uniform processes 

and systems to enhance the value of clinical data,

improve the consistency and interpretation of collected data, and expedite adoption of important

research recommendations. Industry must collaborate with academia in this research because these

groups sponsor and/or conduct the majority of 

pharmacological research in this country.

GENDER CONSIDERATIONS

IN THERAPEUTIC

ADVANCES

A vaccine offering protection against serious 

illness, an effective drug treatment for HIV/AIDS

patients, a diagnostic test capable of detecting a treatable disease at its earliest stage, and artificial joint

replacement devices are examples of therapeutic and

diagnostic advances that offer immeasurable benefits 

for the health and quality of life of all Americans. 

But as these “miracles of modern science” are developed and used, important gender-related questions

must be asked. Are the side effects of a vaccine the

same for men and women? Do men and women react 

in the same way to new HIV/AIDS drugs? Are the therapeutic products that have become standard clinical 

care appropriate and advisable for women? Should 

artificial joint devices be designed differently for male

and female patients? The answers to these questions 

are the essence of this discussion because, in fact, 

many therapeutic advances are put into use and 

continue to be used without consideration of 

gender differences in response to these products.

Concept to Marketplace

The following recommendations encourage a more

deliberate assessment of new therapeutic products as

they affect women and call for ongoing assessments

that consider women’s health perspectives:

• Keep consumers safe. Make gender-specific analysis of safety and efficacy data and identification 

of outliers a critical element prior to any transfer 

of new therapeutic products to the marketplace.

• Identify and evaluate therapeutic products that

warrant further research based upon the ORWH

agenda. Assess, in a systematic way, which therapeutic products are obsolete, not effective, used

inappropriately, or warrant dosage reductions in

women or in other subpopulations at risk.

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CLINICAL TRIALS

As for all medical technologies, clinical trials are 

a key stage in the introduction of new therapeutic

products. Such trials raise many crucial overarching

questions. For example, how can research designs be

modified to encourage greater involvement by women

(i.e., clinical trial participation)? How can we increase

the statistical power to detect meaningful gender differences? Coming up with increased statistical power to

analyze the data by gender will involve more than just

including women. Current clinical trials are not sufficiently large or of sufficient duration, in general, to

detect rare or delayed adverse events, regardless of 

gender. Which populations of women are not now 

participating in trials? Which populations of women

cannot be analyzed in trials because of a lack of statistical power to separate their safety profile from 

the average responder? Can new kinds of trials be

designed? What ethical and social issues are involved?

Recommendations to improve the process include:

• Re-assess the adequacy of current dosage recommendations of approved drug products to optimize

dosages for women.

• Improve the quality of study design, data collection, analysis, and re-analysis of the data.

• Establish databases that include analysis of data 

by gender, hormonal status, age and race, and 

clinical outcomes.

Identification and Quantification of Risks Associated

with Use of Pharmacological Agents

Current methods to detect adverse events include

reviews of case series, qualitative summaries of safety

data from clinical trials, voluntary reports, and epidemiologic studies of suspected agents. Scientific research

is needed for developing improved methods to monitor,

identify, and quantify hazards associated with use of

pharmacologic agents. More sensitive methods are needed to identify high-risk subgroups (e.g., variations in risk

by gender, age, race, concomitant medical conditions)

as well as drug-drug and drug-nutrient interactions.

Limitations of Clinical Trials. Clinical trials may 

have sufficient statistical power to detect differences 

in primary efficacy endpoints but not enough power 

to detect rare or delayed adverse events. The safe use 

of a drug or biologic agent may be determined by 

complex interdependent factors including pharmacokinetics; pharmacodynamics; drug dose; adaptation;

demographic characteristics such as gender, weight,

age, and race; immune response; and concomitant 

conditions or medications.

Lack of Standardized Data Structures. There is 

a pressing need to standardize databases to enable

analysis, comparison, and merging of data. Prescribers rely on clinical trials as the major source 

of information on which to base medical decisions, 

yet tremendous amounts of information in clinical 

trials remain untapped, including information 

critical for women’s health.

Voluntary Reports of Adverse Events. A recent 

meta-analysis to estimate the incidence of serious

adverse drug reactions (requiring hospitalization, permanently disabling or fatal) in hospitalized patients

suggests that the problem of adverse drug reactions

(ADRs) may be more urgent than previously thought.

“Outcome measures that have meaning for

women with a chronic disease (such as arthritis) must

include a measurement of functional status and an

assessment of their quality of life.”

Brenda Crabbs

Arthritis Foundation
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Researchers examined four electronic databases and

found the overall incidence of ADRs to be extremely

high, with serious reactions affecting nearly 7 percent

of hospitalized patients. Additionally, on the basis of

several studies reporting an increased incidence of

ADRs among females, these researchers suggested 

that women could be at greater risk than men.

Recommendations for clinical trials include:

• Develop improved and more sensitive systems 

for collecting and analyzing adverse events by 

gender, age, hormonal status, and race.

• Organize a multidisciplinary “think tank” that

includes the NSF (an agency experienced in 

analyzing large databases in real time, such 

as the visualization of the Mars landing).

• Identify all elements essential for a complete comprehensive data structure. Develop one common

language, such as a medical informatics system, to

be used in all forms of clinical recordkeeping and

reporting from clinical trials, hospitals, HMOs,

Medicaid and Medicare databases, case-control

studies, large longitudinal databases, and systems

for collecting adverse events. This effort should

include standardized nomenclature for therapeutic

agents. As part of developing such a system, various cost incentives for implementation need to be

considered. In order to collect and study clinical

outcomes in subpopulations, the common language would have to be sensitive to gender, age,

weight, menopausal status, use of hormones, 

and race and ethnicity.

Research goals:

• Develop a common standardized database structure for clinical trial data from research to clinical

practice and implement it throughout the health

care system to improve the quality of data and 

to simplify timely data retrieval and signal 

generation analysis.

• Develop strategies to improve the quality of 

reporting adverse events.

• Develop population-based record linkage systems

that can be used to assess the incidences of adverse

drug reactions, compare and evaluate risk factors,

and assess the changing prescribing patterns

among health care providers.

• Develop systems for analyzing large amounts of

data to detect differences by gender, age, and race

in rates of serious adverse events caused by therapeutic agents used either alone or in combination. 

• Develop tools that will systematically screen and

analyze available databases during the postmarketing period (after a drug is approved for use) for

identification of “higher than expected” risks 

associated with the drug combinations.

• Develop data mining techniques that are capable 

of detecting patterns of associations in large databases to systematically screen these databases for

the presence of gender-specific adverse events 

and for drug interactions.

• Consider a new system and entity for postmarketing surveillance that will (a) foster cooperation

among existing postmarketing surveillance programs, (b) develop new methods for carrying 

out surveillance, and (c) train scientists in the 

disciplines needed for doing safety analysis 

of clinical trial data for performing postmarketing surveillance.

• Cause-of-death rankings accounting for ADRs 

in hospital patients should be assessed with 

a gender component.

• Implement prospective methods for collecting 

data on drug use in pregnancy. 

• Conduct research to assess potential adverse effects

on mother and fetus of dietary supplements taken

most frequently by pregnant women.
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COMMUNICATION 

AND OUTREACH

Communication of therapeutic and diagnostic

advances and outreach to health care providers, health

professionals, and the public remains an enormous

challenge. The best ways to disseminate objective 

information on therapeutic advances after they reach

the marketplace have not yet been found. Practitioners

are hard-pressed to keep informed and current on the

range and volume of developments in therapeutic

advances as well as changes in the standards of care. 

In addition, translation of technical information into

lay terms must accommodate the needs of different

audiences, with the role of the media being a significant factor. The interests of those outside the scientific

and business worlds need to be taken into consideration and served. Meaningful forums must be developed

for the exchange of information between and among

scientists, practitioners, and consumers.

Recommendations to improve these channels 

of communication include:

• Establish Internet outreach to consumers and

health care professionals on up-to-date safety 

information, including labeling changes. Link 

commercial company advertisements to this 

web site.

• Network with private and academic institutions

such as poison control centers and schools of 

pharmacy and medicine to gather adverse event 

data efficiently.

• Continue to sponsor dialogs among clinicians, 

scientists, advocacy groups, managed care providers, insurers, and other parties to improve 

overall communication on such topics as concepts of safety and efficacy, concepts of risk 

and benefit, and consequences for both the 

individual and society.

• Continue to seek input from diverse populations 

of women regarding their most pressing health

needs and concerns to ensure their inclusion in 

the research agenda.

• Work with health educators to integrate genderbased science into the curriculum.

• Provide patent extension when a firm improves

safety profile of the drug.

• Determine the best way to inform health care providers and consumers about risks and side effects.

Education of Health Care Providers

There is a lag between basic scientific research 

and its application in the health care setting. Training

and education programs are needed to ensure that 

pertinent research results are properly disseminated

and integrated into health care practice. Additional

education regarding the proper prescribing of medications is needed for nurse practitioners, physician

assistants, and pharmacists.

Recommendation:

• Develop improved training and continuing 

education programs for health care providers.

Research goals:

• For optimal health care of the patient, it is 

essential that the following organizations work

together to teach health care students optimal 

safe and effective use of pharmacologic agents:

American Association of Colleges of Pharmacy,

American Association of Medical Colleges, 

National League for Nursing, and American 

Association of Dentistry Colleges. 
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• Increase continuing education activities and

requirements for practicing health care providers 

to update their knowledge about pharmacologic 

and biologic agents.

P A TIENT CARE

The cost effectiveness of treatment is an essential

part of consideration in clinical care, particularly in the

managed care environment. But the question remains:

When are technologies advanced enough to gain status

for third-party reimbursement? Clinical practice guidelines, which recommend appropriate practices based

on existing scientific peer reviewed literature and clinical experience, should incorporate gender as a variable.

There is need to define quality and outcome measures

that are broader and more sensitive to women’s needs

and that are better measures of quality of care.

Recommendations:

• Involve a broad constituency in developing 

professional practice guidelines that have 

gender-specific components.

• Identify quality and outcome measures that 

are broader and more sensitive to women’s 

diverse needs.

• Propose improvements to existing technologies 

and standards of care based on new information 

on gender differences.

Gender Effects on Drug Compliance and 

Drug Access

Research is needed into factors that may be 

barriers to appropriate care among women.

Recommendation:

• Clarify effect of gender on compliance and access.

Research goals:

• Establish whether gender is a significant factor 

in compliance and, if not, identify other factors

useful as predictors of compliance for women.

• Determine if gender is a factor in successful access 

to therapeutic agents and, if so, ascertain causes 

of this phenomenon.

• Investigate factors that may present barriers to

appropriate care among women, including physicians prescribing behaviors, ability to pay for

medications, educational level, health literacy, 

age, concomitant medications and conditions,

functional limitations, and social support.

Crosscutting Issues and recommendations

Crosscutting Issues

and Recommendations

The differences to be discovered between 

men and women in health and disease are 

not deficits, but provide avenues for new

analysis and treatment interventions tailored to the

group, the individual, and the circumstances.

RESEARCH AGENDA 

RECOMMENDATIONS

Clinical Trials

Enroll more women in efficacy and safety trials,

including pregnant women. This recommendation 

contains two implications: (1) conduct more clinical

trials on women’s health issues and (2) enroll more

women in clinical trials in which men have previously prevailed in numbers.

• Subject participation and compliance. Conduct

research on how to increase recruitment and 

retention in clinical trials and how to enhance 

compliance with treatment regimens.

• Clinical trials of treatment protocols. Undertake 

well-controlled clinical trials with gender-sensitive

models (single vs. mixed gender, mixed gender,

gender sensitivity absence or presence).

• Inclusion of gender as a research variable. Develop 

an integrative strategy to include women in all

phases of research, including both biological 

and biomedical studies.

• Effect of combination therapies on prevention and 

treatment. Conduct human research on incremental effectiveness and safety of combination

therapies. These combinations include simultaneous administration of calcium, vitamin D, 

male and female hormones, and visphosphonates or other pharmaceutical agents.

• Treatment models. Expand research examining 

the development and effectiveness of treatment

models, specific to the unique needs of women, 

for treatment of psychiatric disorders such as

depression, anxiety, PTSD, and eating disorders.

These models must also be culturally relevant 

and address developmental life span issues.

• Stratification of data. Stratify future and existing

data from basic and clinical studies for sex and 

age of subjects.

Specific Populations of Women with Particular 

Health Care Needs or Concerns

Identify the potential differences in each specific

population and how these affect health needs, health

outcomes, and health behaviors across the life span.

Specific populations include medically underserved

women (such as homeless women and women living 

in poverty and in rural areas), women of color, women

with disabilities, adolescents, postmenopausal and

elderly women, lesbians, women with somatic and/or

developmental disorders, and women in jails. These

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women have special treatment needs and are at much

greater risk than women with greater economic

resources, and they may have different etiologies,

needs, and outcomes compared to middle-class 

women from easy-to-reach populations.

• Diversity. Address diversity in all research studies.

Many measurement tools were normed on Caucasian male reference groups. Re-examine these

tools and validate them for use with females and

diverse ethnic groups. Similarly, there is need for

female-centered models of treatment. In developing these models, researchers need to be cognizant 

of the variables important in women’s mental

health, including race, religion, socioeconomic 

status, and sexual orientation.

Multidisciplinary Research

Collaborate with colleagues from other disciplines

to expand and strengthen research; include behavioral

and social science components in research.

• Alcohol and other drugs and biological effects. Develop

collaborative research programs to examine the

relation of alcohol and drug use to biological

effects; gender differences; psychosocial, behavioral, cognitive, psychiatric, general health, 

family, and legal consequences; specific sexually

transmitted diseases; and reproductive effects.

• Resource sharing. Increase sharing of resources

among researchers — including sharing of clinical samples, DNA banks, serum banks, animals,

and reagents.

• Collaboration. Foster interagency and public-private

collaboration in order to carry out the full range of

research recommended for studying health issues

in women, including pregnant women.

Information Systems

Design information systems that allow easier access

to archival material on clinical and genetic studies.

RECOMMENDATIONS

THAT SUPPORT THE

RESEARCH AGENDA

• Women’s life cycle. Ensure that research on women’s

health takes into account the full biological life

cycle of the woman and the concomitant physical,

mental, and emotional changes that occur. Easily

identifiable stages in a woman’s life include: prenatal, infancy, childhood, adolescence, childbearing

potential, pregnancy, lactation, perimenopause, 

postmenopause, elderly, and frail elderly.

• Training and career development. Develop new program announcements to encourage career opportunities for women in research. Continue to provide

supplemental research training and funding opportunities to women who must often interrupt their

careers because of family care responsibilities.

Establish mentoring programs for girls to encourage them to pursue science courses and careers,

including programs linking high schools to universities. Develop research and clinical research

training programs targeted for women.

• Education. Educate the public and health professionals to optimize the choices of management 

in reproductive health and diseases. Health care

providers need to be fully, yet critically, informed

about advances in their fields including risk factors, diagnostic tests, treatment options, and followup strategies, to best advise consumers about

their care. Consumers need the information to

understand the pros and cons of options available 

to them, for example in contraception, management of pregnancy and delivery, and menopause,

as well as in diagnosis and treatment of infertility

and other reproductive diseases and disorders.

Develop, evaluate, and carry out educational and

intervention programs that are sensitive to an individual’s cultural and socioeconomic background.
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• Communication. Foster improved communication between the lay public and the scientific 

community, making information readily accessible to researchers, health care providers, 

and consumers.

– Among professionals: Facilitate communication among investigators, clinicians, patients,

and the public. Clinicians frequently define

observations needing laboratory explanations,

while promising laboratory developments 

need timely clinical evaluation.

– With patients and public: Teach health care providers skills in communicating risks and in

encouraging health-promoting behavior to 

their patients and the public.

• Evidence-based medicine. Facilitate evidence-based

medicine; disseminate and integrate research

results into practice patterns.

• Prevention. Focus research on a continuum of 

prevention methods, ensuring that prevention 

messages are culturally appropriate.

VOLUME 1

ORDER 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 

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M 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.

M 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.

M Volume 3 — Agenda for Research on Women’s Health for the 21st Century, Public Testimony; Bethesda, Maryland:

November 1997; NIH Publication No. 99-4387.

M 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.

M 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.

M 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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