Minding the gender gap: The divergence between men's and women's health research

Vive la difference!

Science is pointing out new ways to celebrate differences -- specifically those between the sexes -- and recognize that these differences go far beyond the reproductive system to permeate every part of the body. Researchers think that understanding those variations could result in changes in the way all sorts of diseases are diagnosed and treated.

Why should being dealt XY or XX chromosomes at birth have such an all-pervasive influence? The question is intriguing several researchers, and what they uncover could help make all-too-brief office visits more productive for primary care physicians and their patients.

For example, recognizing that 20% of women experience a heart attack by having pain in the upper abdomen could change doctors' responses when female patients complain of indigestion, extreme shortness of breath, sweating and nausea.

"If you're not tuned in, you'll do a gall bladder series or give an antacid for the indigestion and a Valium for the hyperventilation," said Marianne Legato, MD, founder and director of the Partnership for Gender-Specific Medicine at Columbia University in New York City. The center is a joint effort by Columbia and private sponsors including the W.K. Kellogg Foundation and Procter and Gamble.

The move toward the study of sex or gender differences -- some speculate that the latter term is used to distinguish these centers from Web sites with a more salacious goal -- represents a sidestep away from the more traditional women's health centers that often were formed to promote the inclusion of more women in clinical trials.

"The science of gender-specific medicine is not women's health, but it recognizes that men's and women's experiences with the same disease and course of treatment are different," said Dr. Legato, also a spokeswoman for Embracing Women's Health, a Web-based information site.

"Women's health is expanding into the larger concept of gender-specific medicine," noted a recent report by the National Institutes of Health's Office of Research on Women's Health.

"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," according to the report.

Even some of the women's health groups formed several years ago have broadened their view. "For us, it's not men's versus women's health, it's men's and women's health," said Sherry Marts, PhD, vice president for scientific affairs at the Washington, D.C.-based Society for Women's Health Research. "Understanding what the differences are and how important they are in terms of health and disease is obviously going to benefit everybody."

Emerging differences

The exploration of sex differences is still a new field, and information, such as the different heart attack symptoms, is beginning to emerge. As a result, some conventional wisdom is changing, though it does take time for good trials to be run and their data analyzed. Plus, the NIH didn't require that women be included in clinical trials until 1993. It was even more recently that the Food and Drug Administration began stipulating that research on women of childbearing age be analyzed in drug trials.

Also, for years, medical textbooks had no mention of differences between the sexes until the chapters on reproduction, Dr. Marts said. "It was all supposed to be the same. Well, we know now that's not true. We certainly know it's not true in the brain. We know it's not true in the lungs. We know it's not true in the heart. It's probably not true anywhere. I imagine our toenails are different."

The AMA Council on Scientific Affairs explored such concepts in a report drafted in 2000. Among the general trends and risk factors for disease recognized in the report: The risk for heart disease increases for women after menopause; women are at much higher risk for autoimmune diseases; and they are more susceptible to the damaging effects of cigarette smoke and alcohol.

Studies of these differences already have yielded a number of clinically useful findings. For example, information recently released by the American Heart Assn. shows that scheduling an exercise electrocardiogram might not be the best approach to diagnose coronary artery disease in women. "In women who are able to exercise, it is still useful, but its utility is dependent upon the woman's exercise capacity," said Jennifer H. Mieres, MD, chair of the AHA committee that wrote the new statement on women and heart disease.

"Heart disease continues to be the leading cause of death in women, and when we look at all types of heart disease, coronary heart disease is the largest subset of this mortality, claiming the lives of an estimated 240,000 American women each year," Dr. Mieres said.

Yet women who are at risk for coronary heart disease or coronary artery disease often are not referred for appropriate diagnostic testing, perhaps because physicians are more familiar with using imaging studies to evaluate men, she said.

Meanwhile, Dr. Legato also noted that women with diabetes are not protected from coronary disease by virtue of younger age. Coronary disease generally occurs 10 years later in women than it does in men.

In addition, "Every diabetic patient, whether male or female, should be considered to have and be treated as though he or she has coronary disease, which means statins, beta-blockers, aspirin and so on," she said.

Men also face decided shortfalls when it comes to adequate medical evaluation of depression, some men's health experts say. Physicians should understand that discussion of depression and suicide deserves attention, said Jean Bonhomme, MD, MPH, a member of the research faculty at Emory University in Atlanta and founder of the National Black Men's Health Network.

"Men commit suicide at least four times as frequently as women do," he said. "I think we miss a lot of sadness and depression, and therefore there is a lot of suicide in men."

Dr. Legato agreed. "Men and women evidence depression in different ways," she said. "Women are much more likely to discuss their troubles or depression with others. Men become more solitary and may turn to violence and drinking."

There is also a well-recognized gap between men's visits to their physicians and women's visits -- men simply don't go. So to receive a benefit from research into sex differences, men must be persuaded to take advantage of any findings.

"Enlisting the whole family can encourage men to come in," Dr. Bonhomme said. "You'd be surprised at how many calls I get from children saying, 'My father looks terrible. How can I get him to come in?' "

Enlisting family members also can be instrumental in getting men to follow a medication regime. "Sometimes I'll tell a guy to take medicines at a certain time or with meals and [I] get a look like a deer caught in the headlights. Men are not accustomed to self-care," he said.

Dr. Bonhomme remains a proponent of establishing an NIH Office of Men's Health to complement the Office of Women's Health. "I think an Office of Men's Health could raise the profile of specific issues facing men."

Exploring the whys

But the understanding that the effects of gender on the body are so far-reaching led Georgetown University Medical School in Washington, D.C., down a different path. In December 2003, the institution established a broad, multidisciplinary Center for the Study of Sex Differences in Health, Aging and Disease.

Its director, Kathryn Sandberg, PhD, is particularly interested in how sex differences affect blood pressure and, in turn, hypertension's effects on cardiovascular and kidney disease. She and her colleagues are exploring why, as women age, and particularly after menopause, they tend to experience a significant increase in blood pressure and associated cardiovascular events.

The Georgetown center is also looking at the manifestation of HIV infection in men and women and the more deadly consequences of lung cancer for women.

Recent studies also have indicated that women could be at greater risk for arrhythmias in reaction to methadone. Discovering the cause might prove key to understanding why arrhythmias are occurring in both men and women, according to center researchers.

In addition, women are much more likely to have an autoimmune disease, and physicians would do well to delve into any family medical history of rheumatoid arthritis, lupus, multiple sclerosis or even type 1 diabetes, Dr. Marts said.

"So you could have a cousin with lupus, your Mom has MS and you end up with rheumatoid arthritis. What they all have in common is that they are autoimmune conditions," she said.

In addition, MS may affect men a little differently than women, she noted. "Women tend to get it in their 30s in the form that relapses and remits. While some men get that form, they are more likely to show symptoms in their 40s and to continue to get worse."

Dr. Marts is also interested in knowing whether sex differences could have influenced the cardiovascular side effects that led to the withdrawal of the pain killer Vioxx and the suspicion cast on the other COX-2 inhibitors. "Those data, as far as we know, aren't available yet."

But the important lesson to be drawn now is to keep looking. "The more you pay attention to, the more you find," she said.