Women, Men, and Medicine: We're Not Equal

What Is Gender-based Biology?

Gender-based biology is the field of study that looks at the biological and physiological differences between the sexes. Researchers are looking past the basic XY/XX chromosomal difference that makes a man a man and a woman a woman and are finding variations at the system, organ, tissue, and cellular levels.

Phyllis Greenberger, executive director of the Society for the Advancement of Women's Health Research, comments, "The findings from gender-based biology have the potential to revolutionize the way we understand health and disease for both men and women. The differences extend beyond the obvious to areas such as the reaction to specific drugs, how men and women respond to the same disease, or metabolize the same compounds. The more scientists look for such differences, the more they find, and the more they recognize how important those differences are."

The Male Model of Research

Traditionally, medical research has been conducted using a male model as the basis for clinical studies. Citing concerns of potential harm to unborn children and to reproductive capacity, the FDA has always banned women of childbearing age from participating in safety tests of new drugs. This exclusion became common practice among scientists who claimed that a woman's fluctuating monthly cycle would interfere with their research.

The findings of their studies, nonetheless, were applied across gender, and healthcare providers assumed a one-size-fits all approach in treating both male and female patients. There also was a general inclination to think of a woman's well being in terms of reproductive health. Symptoms of other illnesses were ignored or attributed to hormones, and women often were told that such symptoms were "all in their head."

The Beginnings of Change

Over time, though, scientists began to accumulate evidence indicating that illness and disease may not affect both sexes similarly and that findings obtained from studies based on men may not always apply to women. However, due to the lack of clinical studies involving women, these claims were difficult to substantiate. Washington responded by developing guidelines for the inclusion of women in federally funded clinical studies and in 1990 established the Office of Research on Women's Health (ORWH) at the National Institutes of Health (NIH).

Specifically, the ORWH was charged with the following:

• Eliminating gaps in knowledge by determining an appropriate research agenda for women's health.
• Ensuring that, regardless of cost, women are represented in NIH clinical studies.
• Increasing the number of women in biomedical research careers.

What We're Learning

Although current research efforts in gender-based biology focus primarily on identifying differences, scientists are beginning to find possible biological and physiological explanations. Here are some examples:

• Women are more likely than men to suffer from depression due to a lower rate of serotonin synthesis in the brain.
• Women produce less of the enzyme that breaks down alcohol in the stomach, which may explain why, on consuming equal amounts of alcohol, they have a higher blood alcohol level than their male counterparts.
• Language centers are positioned in different areas of the male and female brain, suggesting a possible answer as to why women suffer less aphasia than men following a stroke.

A Word of Caution

But Greenberger cautions, "We have more questions than answers right now. It would be premature to expect a physician, who, for example, is treating depression, to say that since we know that serotonin synthesis is affected by a woman's cycle, we know that she should receive only a half dose of medication during the luteal phase. More research, in the form of clinical trials, is needed before we can translate what we now know into treatment." She adds that women should share any information they find with their doctors and discuss options.

Putting New Information to Work

The good news is that researchers have made significant progress in understanding cardiovascular disease—the number one killer of both men and women. For example, we now know that of all heart attack victims under the age of 50, women are twice as likely as men to die from the attack.

Studies suggest that this may occur because women are

• Less likely to take medications or aspirin to prevent heart attacks
• Slower to seek treatment at the onset of an attack
• Less likely to receive critical diagnostic procedures, such as angiography or cardiac catheterization, once at the hospital.

Scientists also are discovering some things about women that may help to counter this trend.

• Symptoms
• Women do not always exhibit the classic male symptoms of a heart attack—severe squeezing pain and uncomfortable pressure or fullness in the center of the chest. Rather, women may experience silent symptoms: shortness of breath, fatigue, discomfort, nausea, dizziness, or pain in unlikely places such as the jaw. Since these symptoms have long been associated with illnesses other than heart disease many physicians may not recognize them as such. Therefore, a woman who suspects otherwise would be right to ask for a full cardiac work-up if she presents with these symptoms and is told that she has indigestion.
• Testing
• Similarly, we now know that the exercise stress test—long considered the gold standard in diagnostic evaluation—can produce a high rate of false positive results in women. The echo stress test is now recognized as a more precise tool for evaluating the female heart.
• Medication
• The drug Integrelin, which is used to treat unstable angina, is more effective in women than in men, and women metabolize the drug propranolol (used to treat cardiac arrhythmias) slower than men.
• Drugs in the Prozac family, selective serotonin reuptake inhibitors (SSRIs), rise to higher blood levels in women than in men.
• The anti-inflammatory drug ibuprofen is less effective in women than in men.
• Use of oral contraceptives may affect the action of many other drugs.

Looking Ahead

For the future, Greenberger looks for scientists to continue identifying gender differences and learning how and why they occur. Encouraged by the efforts of the ORWH, she expects greater participation of women in healthcare and medical research, which will add a much-needed second perspective to clinical studies. Lastly, Greenberger hopes that gender-based biology will be seen not only in terms of women's health, but also as a means for better understanding the mechanisms of disease in both sexes. And this, she feels, will help us move beyond health by the books toward health according to our sex.