April 2003

A Word to the Wise... Participating in Clinical Trials If you are a woman interested in participating in clinical health studies, go to http://clinicaltrials.gov/. There, you can search for studies on particular diseases and conditions, or you can type the word "women" in the search box and browse through the hundreds of clinical trials listed. The web site also includes other information to help you understand more about clinical trials and how to participate in them.

Attitudes, Models of Women's Health Continue to Evolve Dr. Marianne Legato, founder and director of the Partnership for Gender-Specific Medicine at Columbia University's College of Physicians and Surgeons in New York City, lists several milestones in the "short, powerful and recent" history of women's health: In 1900 the average life expectancy for a woman was 48. At the time, menopause or diseases of aging were not a priority. "The focus was on maternal survival in childbirth, survival of infants and small children, infectious disease, and conditions that arose from poor public sanitation," Dr. Legato said. World War II and the period immediately after triggered a number of significant gains for both women and medicine, Dr. Legato said. "It was inevitable that the parallel phenomena of feminism and the explosion of American science and technology would grow out of World War II." In 1979, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research said in its Belmont Report that if women were to reap the benefits of research, then as a matter of justice, they would have to take the risks of participating as subjects in clinical investigation. Efforts to study the biology of women exclusively are far more recent, Dr. Legato said. "The preeminence of women's health has only been accomplished since 1985," she noted, citing conclusions from the Public Health Service Task Force on Women's Health Issues. The task force found that "heightened emphasis on disease prevention and health promotion in areas beyond the pregnancy and infant health category can provide a significant source of information for women, as well as facilitate longer term benefits." In 1994, the Institute of Medicine (IOM) released a monograph titled Women and Health Research: Legal and Ethical Issues of Including Women in Clinical Studies, which Dr. Legato called "the first thoughtful reflection on the possibility that men and women might experience disease differently." The document also forecast where a limited view of women's health might lead: "Our moral analysis of our practices considering the inclusion of women in clinical research will fail to capture all that it should, if we restrict our focus to the charge of exclusion and underrepresentation." Last year, an IOM Committee on "Understanding the Biology of Sex and Gender Differences" concluded in its 2001 report: "Sex does matter. It matters in ways that we did not expect. Undoubtedly, it also matters in ways that we have not begun to imagine."

What's Next for Women's Health Research?
by Carla Garnett

Is women's health relevant to the general health of everybody or should it stay rooted merely in women's health centers? That's the question the medical science community must now ask, according to Dr. Marianne Legato, who lectured recently at the National Institutes of Health. Dr. Legato, a cardiologist who founded and directs the Partnership for Gender-Specific Medicine at Columbia University's College of Physicians and Surgeons in New York City, said the answer is both simple and complicated: Gender matters.

"You never would imagine the scope and significance of the differences between men and women in all the systems of the body," Dr. Legato said. "Being male or female is not simply a question of hormones."

For example, the size, structure and function of the brain differs in women and men, Dr. Legato said. Whole brain volume and the corpus callosum (the broad, thick band containing millions of nerve fibers running from side to side in the brain) are about 20 percent larger in males than in females. Women, however, have more neural connections across the corpus callosum.

"The variations in the gross volume of the brain are most significant in the areas that have to do with mood and behavior," she explained. These differences could have implications for diagnosing and treating such disorders as depression.

Men and women also sometimes use different areas of the brain to perform the same tasks. For instance, when asked to use verbal memory skills, women activate the left hemisphere of the brain and men activate the right hemisphere. Dr. Legato said reaction time is slower in women, but accuracy is higher.

"What does it mean?" she asked. "Does it mean differences eventually in the way that we will educate and communicate with men and women? We don't know. Does it mean that there are real gender differences in ability? That's a hotly debated issue. What is clear is that in some instances men and women recruit different areas of their brain to perform equal tasks."

Differences Throughout the Body

The biological differences between men and women extend through many systems in the body. For example, bone mass in a woman peaks at a distinct age, usually when she is in her early 20s. By contrast, a man reaches his maximum bone density much more gradually and plateaus later, by age 30. A period of accelerated bone loss occurs in women at menopause and continues for about five years afterward. These differences could prove important to understanding such disorders as osteoporosis.

"What is not clear is whether the bone loss is related only to estrogen deficiency," Dr. Legato explained. "Counseling therefore could differ [for men and women] on how and when to adjust lifestyle to achieve and preserve maximum bone density."

A woman's cardiovascular system, too, is different from a man's. The size, shape and electrical systems of the heart all vary in some respects by gender. Women have faster heart rates than men. These differences could prove to be crucial considerations in preventing, diagnosing and treating heart disease, the nation's top killer of both sexes, Dr. Legato said.

The differences don't end there. Women experience pain in different ways than men do, females seem more prone to autoimmune disorders than do males, and a woman's responses to infection varies from a man's responses. Even some specific diseases, such as malaria and HIV/AIDS, manifest themselves differently in women and men, Dr. Legato noted. These variations — and others yet to be discovered — are why scientists should examine the emphasis placed on women's health in the past two decades, she said, and determine whether research has taken into account all aspects of female biology.

Moving Beyond the "Bikini View"

"What does women's health really mean?" Dr. Legato asked. "Does it go beyond the ‘bikini view,’ that is, breast health and reproductive biology?" She suggested that new forays into gender-specific research must take broader, multidisciplinary approaches and look at women across their entire lifespans.

The Agenda for Research on Women's Health for the 21st Century, a report prepared by the NIH Office of Research on Women's Health (ORWH) with the input of more than 1,500 women's health professionals and advocates in the US, reflects Dr. Legato's suggestion. Spanning behavioral and social as well as biomedical research, the agenda recommends addressing health issues across a woman's life, "from prenatal stages to the frail elderly." The report also emphasizes the importance of understanding both genetic and environmental factors in determining how diseases develop, grow and spread.

Major diseases — heart disease, cancer, mental disorders and musculoskeletal problems — top the agenda. Several "emerging directions for improving women's health" — such as prevention and disparities among diverse groups — are also suggested in the report. Experts are convinced that implementing such a comprehensive plan for women's health will profit everyone's health.

"The women's health movement is a movement that I think can and will bring benefits to all members of our society," concludes Dr. Vivian Pinn, NIH associate director for research on women's health and ORWH director.

—a report from The NIH Word on Health, April 2003

For copies of the Agenda for Research on Women's Health for the 21st Century, an eight-volume report and forecast on womens' health issues, visit http://www4.od.nih.gov/orwh/report.pdf or contact:

Office of Research on Women's Health
Office of the Director
National Institutes of Health
1 Center Drive, Room 201, MSC 0161
Bethesda, MD 20892-9663
Fax: 301-402-1798