Many drugs are tested on men only, creating grave doubts for female patients

By Andrew Purvis--With reporting by Julie Johnson/Washington

One morning two years ago, a 60-year-old woman in Madison, Wis., asked her doctor what seemed like a simple question. The patient had just reached menopause and wanted to know whether she should start taking aspirin daily. She had seen newspaper and TV reports claiming that the pills lower the risk of heart attacks, and she knew such risks increase dramatically for women after they stop menstruating. "My answer was dead silence," says the woman's physician, Dr. Elizabeth Karlin, who teaches at the University of Wisconsin medical school. A week later, after scouring the literature, Karlin came to what she called an "appalling" conclusion: the finding, trumpeted in some newspapers as a lifesaver for everyone, was based entirely upon research on men. "There were simply no data to say this was safe for women."

Karlin had discovered an information gap that may be endangering millions of American women. A number of treatments now recommended for men and women--from cholesterol-lowering drugs and diets to AIDS therapies and antidepressants--have been studied almost exclusively in men. Little hard evidence exists about their efficacy or safety for women. The problem has begun to concern doctors, patients and now lawmakers. In June Congress's General Accounting Office released a report condemning the National Institutes of Health (NIH) for failing to promote studies that took adequate account of the differences between the sexes. The Congressional Caucus for Women's Issues, which commissioned the study, introduced a $237 million legislative package in July aimed at achieving "parity in medical research." Said caucus co-chair Patricia Schroeder of Colorado: "Doctors aren't getting the kind of guidance they need when they try to prescribe for women."

Medical testing done entirely with male subjects may be adequate when a disease strikes women and men in the same way, but a growing body of research shows that this is often not the case. Some preliminary studies on depression, for example, suggest that hormonal changes in many women may lead to a premenstrual deepening of depression. Further research on appropriate doses of antidepressants throughout the menstrual cycle is needed, says Dr. Jean Hamilton, a Washington-based neuropharmacologist, to determine if female patients are getting adequate medication.

Women's hearts also differ markedly from men's. Not only does cardiovascular disease strike women later in life, but blood cholesterol levels seem to play a somewhat different role in female patients. Dr. John Crouse, a lipids researcher at Bowman Gray School of Medicine in North Carolina, notes that women seem to be less vulnerable than men to high levels of LDL, the so-called bad cholesterol, and more vulnerable to low levels of HDL, the "good" cholesterol. Diets that reduce both levels, such as the one promoted by the American Heart Association, may actually harm women, Crouse argues. The dearth of data on women and heart disease may also have contributed to an alarming problem: women are significantly more likely than men to die after they undergo heart-bypass surgery. One reason, suggested a study last spring, is that doctors are slower to spot serious heart trouble in their female patients and slower to recommend surgery.

Many researchers complain that the billion-dollar federal onslaught on AIDS has also underrepresented women. At a time when women are the fastest-growing group afflicted by AIDS, there are troubling uncertainties about whether treatments or the disease itself are affecting women differently from men. Some studies, for example, have suggested that women with the virus die more quickly than men, and from a somewhat different range of opportunistic infections. "Drugs are developed with incomplete data on metabolic differences between the sexes," charges Congressman Henry Waxman, a major advocate for women's health. "This is not a question of affirmative action. It is a question of well-being."

Why have women been excluded from so many studies? In the case of heart disease, some researchers argue that it is too difficult to find enough subjects with the condition, since it develops later in women. Also, the hormone changes of the menstrual cycle are thought to complicate research, raising costs. Perhaps most important, doctors are worried that if women enrolled in a clinical trial became pregnant, experimental drugs could endanger the fetus.

Critics counter these arguments by asserting that it is worth the trouble and expense of recruiting women research subjects, given that women make up half the population--and half the taxpayers underwriting federal research. Concern for the fetus is often exaggerated, they say. "There is a tendency to think of women as walking wombs," says the University of Wisconsin's Karlin. Most female cardiac patients, she notes, are not planning to get pregnant.

Health concerns that primarily affect women get particularly short shrift in the research community, many doctors say. Breast cancer, for example, has doubled in incidence since 1960 and is now killing 44,000 women each year. Yet last year the NIH spent just $77 million studying the ailment, including only $16 million on basic research. Two years ago, the NIH halted a major study on breast cancer and low-fat diets because of cost considerations. "I can't believe that decision," says Dr. Mary Guinan, assistant director for science at the Centers for Disease Control. "If we could tell women that their diet lowered their risk, we could save thousands of lives."

Research on contraception and menopause has also failed to garner many federal dollars. Though an estimated one-third of older women are taking hormone-replacement therapy to combat osteoporosis and other effects of menopause, many questions remain about how this treatment might alter the risks of breast cancer and heart disease. Says Guinan: "As doctors, we think we're helping women when we may actually be harming them." Meanwhile, no new contraceptive method has been approved in the U.S. since the 1960s. Overall, the NIH spends only 13% of its $7.7 billion budget on women's health issues, according to the Women's Caucus.

Officially, the NIH has had a policy since 1986 of requiring grant applicants to at least "consider" including women in their research. But that policy has been limply enforced. In September NIH acting director Dr. William Raub set up a special office to explore the problem.

For many experts, though, more study simply means more delay. Raub's likely successor, Dr. Bernadine Healy of the Cleveland Clinic--the first woman recommended to head the NIH--has called for "exercising relentless pressure" on researchers and policymakers to fully represent women in health studies. Until that is accomplished, it seems, doctors will have to decide for themselves which presents the greater risk to their female patients: the disease or a cure proven only for men.

Copyright (c) TIME Magazine, 1995 TIME Inc. Magazine Company; (c) 1995 Compact Publishing, Inc.

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