Studying Differences Between the Sexes May Spur Improvements in Medicine

It's hard to believe that only a little over two decades ago, the U.S. government issued guidelines recommending that pharmaceutical companies exclude women of childbearing age from participating in clinical trials. Now the National Institutes of Health has an office devoted to women's health research, and more women are being included in critical medical research. That is progress, to be sure. But it has become increasingly clear that to improve medicine for both men and women, more also needs to be done to study differences between the sexes. For too long, the research community has ignored the fact that being male or female encompasses far more than reproductive systems and hormones. Sexually determined characteristics can be found all the way down to the cellular level, and they have important implications that influence how long we live, how we are affected by disease and medication, and even how our brains function. I recently chaired a panel of the Institute of Medicine that examined the scientific literature on how molecular and biological differences between the sexes affect health. We concluded that it would benefit everyone--men and women alike--if biomedical researchers started paying more attention to these differences. Doing so could identify new ways to promote good health and improve the way diseases are diagnosed and treated. Male and female genomes differ only in the fact that females have two X chromosomes, while males have one X chromosome and one Y chromosome. For years, the Y chromosome was believed to carry only information to determine male sex and to be active only early in fetal development. Similarly, scientists believed that one of the female X chromosomes was totally inactive. Thus, it was thought that the active genome was essentially identical in males and females. Recently, however, it was discovered that both the supposedly inactive female X and the male Y chromosome carry a few genes that are present in both sexes. Obvious anatomical and hormonal differences aside, these genetic differences mean that tissues common to both males and females may have different responses to disease and medication. Studying these differences should shed light on the incidence and prevalence of many diseases and help researchers ferret out the molecular mechanisms involved. Of course, it's obvious why only males can develop prostate cancer, and only females get ovarian cancer. But it's not at all obvious why women are more likely than men to recover language ability after suffering a stroke, or have a far greater risk of developing life-threatening irregular heart rhythms in response to potassium channel-blocking drugs. Sex appears to play a role in the severity and incidence of several diseases, including heart disease, obesity, and rheumatoid arthritis. Sex differences need to be studied at the cellular level to determine how sex influences susceptibility to disease and functioning of organs and organ systems. Being male or female is a basic human variable that should be considered when designing and analyzing studies in all areas of biomedical and health-related research. Scientists often do not know today whether the cells or tissue cultures they are studying came from male or female patients. Researchers should routinely determine and disclose this information. What's more, the biomedicine of sex differences should be studied at all stages of life--from conception to death. There are other areas where specific study could have immediate, tangible benefits. For instance, men and women absorb and excrete certain drugs in different ways and at different rates. Some drugs have more severe side effects in women than in men, and some drugs are more effective in women. Therefore, effective drug dosage must routinely consider sex as well as age and body weight. Until the question of sex is routinely asked and the results--positive or negative--are routinely reported, many opportunities to obtain a better understanding of disease and to advance human health will surely be missed. It is widely known that studies on variables such as sex, age, race, or ethnicity have all too often been biased and have led to discriminatory practices. History must be taken into consideration so that discriminatory practices will not be repeated. Mary-Lou Pardue, Boris Magasanik Professor at the Massachusetts Institute of Technology, Cambridge, recently chaired an Institute of Medicine panel that wrote the report, Exploring the Biological Contributions to Human Health: Does Sex Matter? www.nap.edu/books/0309072816/html/index.html

Studying Differences Between the Sexes May Spur Improvements in Medicine

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