Trained by world-class investigators and scholars at three American premier academic medical centers, I learned that no hypothesis could be accepted as true without rigorously collected and interpreted data that supported the idea. The challenges were always the same: "How do you know that's true? What's your source?" Whenever I planned an investigation, wrote a paper, sat on a National Institutes of Health study section, or taught younger investigators how to do credible research, I emphasized the following: "Make no assumptions. Do the data, no matter how persuasive, lend themselves to another, more credible interpretation?" We tried to be intellectually honest, whether in the laboratory or consulting roombut for one glaring exception: We assumed what we learned about men was true of women and could be extrapolated to females without modification.
How did generations of medical scholars accept that idea? When did we stop asking whether we could treat women as though the data we obtained from men meant we never had to study women at all? We may never even have asked the question. As late as 1994, the Institute of Medicine reported in its classic "Women and Health Research" that two-thirds of all diseases experienced by both men and women had been studied in men only.
The choice of males for an experimental protocol made some sense: Males don't have hormonal fluxes and are a "cleaner" group to study, with fewer variables. A study devoted to one sex is less expensive: One can prove the probable truth of an idea with fewer subjects. And most important in human studies, studying a male doesn't carry the potential danger of harming a fetus conceived during the trial's course or to an adult born of a woman who received a drug, such as diethylstilbestrol, whose late effects could not have been anticipated. Practically speaking, recruiting women for trials was also difficult because they feared harming their reproductive capabilities, while men, apparently, did not worry about such things.
So, a combination of protectionism, economics, and efficiency led us to work mostly on men. It was only pressure by women to have direct, expanded, and accurate information about the unique aspects of their normal physiology and their experience of disease that led us into the 1990s, with the NIH, Food and Drug Administration, and Congress all mandatingand facilitating with expanded and focused supportthe direct study of females whenever it was relevant. The results have been nothing short of astounding. In every system of the body, men and women have completely unexpected differences. Our brains, bones, skin, guts, and hearts are all uniquely constructed as a function of our biological sex. So much so, the Institute of Medicine last year concluded sex is an important variable in research in its "Exploring the Biological Contributions to Human Health. Does Sex Matter?" In fact, the new information about women prompted a Random House imprint last month to publish my book, "Eve's Rib," for lay people about the differences between the sexes. We are now compiling the first textbook on gender-specific medicine for professionals.
As a result of the new data, we are asking questions we never would have asked: If we can unravel why women, on average, live six years longer than men, can we use the information to prolong the lives of men? Why does diabetes increase the risk for coronary artery disease of even young, pre-menopausal women four- to six-fold, while it only doubles it for men? If men and women employ different brain areas when performing an identical task, should we communicate with the sexes differently? So far, the questions are more provocative than the answers, but the new line of inquiry is producing a generation of scientists interested in answering them.
We have not solved all of the problems involved in studying women: We still avoid pre-menopausal women as subjects. The Women's Health Initiative, the ambitious, costly, and more than 12-year-long effort to understand the impact of hormonal replacement therapy and environment (including nutrition) on women's health is devoted entirely to postmenopausal women. But some of us believe that if women are to benefit from medical research, they must also share in the risk of serving as subjects for that research. We must recognize the mistake in the concept that studying women is too dangerous for them (as compared with men) and too expensive and time-consuming for us. By considering the differences between the sexes in research, we are asking new questions. Answering them is shaping a new era in medicine, based on data and not on unfounded assumptions.
Dr. Marianne J. Legato is professor of clinical medicine and founder and director of the Partnership for Gender-Specific Medicine at Columbia University.