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The Invisible Woman

The Gender Gap in Medical Research--Most of our "knowledge" is based on studies that exclude 52 percent of the population. It's not only bad politics, it's bad science.

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The fact that women live longer than men says more about our biology than about the care we receive from the medical establishment. And second-rate health care for women in the United States is the result of systemic discrimination in scientific research: women have been consistently excluded from clinical trials, and gender analysis is usually missing from scientific data. Whether the fault lies with spending priorities at the National Institutes of Health--the major source of funding for biomedical research in the United States--or with a medical establishment that is still overwhelmingly male, the state of women's health care can be summed up in two words: bad science.

Practically all of our medical knowledge has been derived from studies based on white men, even though women, as well as nonwhite men, are different--physiologically, biochemically, and genetically. The headline of a recent article in the Journal of the American Medical Association asks, "Is There Still Too Much Extrapolation From Data on Middle-Aged White Men?" The answer, a growing number of researchers and doctors suggest, is yes.

"Heart disease is studied more in males," says Dr. Estelle Ramey, an endocrinologist and past president of the national Association of Women in Science. "In conducting research in this manner, scientists are in fact studying heart failure in men, and failing to study heart success in women. Studying heart success in women could help us to understand how to make men live longer. So nobody benefits when you exclude women from research protocols or decision making. Nobody benefits when you exclude women as researchers or research subjects."

In 1987 the NIH spent $648 million researching heart disease, the leading cause of death in women and men. Yet almost all recent major studies have been done on men. (A 1989 study, on 22,071 male doctors, determined that aspirin reduces the risk of heart attack; another study, on 45,589 men, indicated that coffee intake did not increase the incidence of heart attacks or strokes; yet another, the Multiple Risk Factor Intervention Trial--"Mr. FIT"--studied risk factors in 15,000 men.) A 1990 American Medical Association report on "Gender Disparities in Clinical Decision-Making" notes that, because there are significant differences in the way cardiovascular disease affects women and men, "The lack of research done specifically on women may have resulted in a failure to develop diagnostic criteria and treatments that are appropriate for cardiovascular disease in females."

"Efforts to streamline studies by using the most homogeneous population possible have filled medical libraries with data on middle-aged white men," writes Paul Cotton in the JAMA article. Even female rats are commonly excluded from basic research, because the hormonal flux of the menstrual cycle is thought to provide a "confounding" factor. Confounding to whom? Looked at from a different perspective--that of 52 percent of the population--it's just as confounding to be confronted with medical data that does not take one's basic biology into account.

Because of this research bias, doctors can't accurately determine whether study results can be extrapolated for women, not to mention elderly and nonwhite patients, all of whom metabolize drugs differently. Yet women are seldom cautioned about taking these drugs once they reach the market. In a 1981 article in the Annals of Internal Medicine, Evlin Kinney and colleagues pointed out this disturbing consequence of excluding women from clinical trials: not only is there an increased risk of side effects to women who take the drugs once they're on the market, but "these women, unlike subjects of clinical trials, will not have consented to the risk."

How is it that women have been left out? In addition to those "confounding" hormones, which complicate research and thus raise its cost, restrictive research and licensing regulations enacted to protect women in the wake of medical tragedies have actually discouraged the use of women in clinical trials. The seriously deformed children born to pregnant women who'd taken thalidomide for nausea in the 60s shocked the medical community as well as the public. It was then discovered that young women born to mothers who'd taken DES, a synthetic hormone used to prevent miscarriages in the 40s and 50s, were developing a rare form of vaginal cancer. Finally, in the 70s, women using the Dalkon Shield intrauterine device began suffering from serious pelvic infections, which can render a woman infertile or cause grave problems during pregnancy. Inadequate research standards have been blamed for the thalidomide and Dalkon Shield disasters; with DES, research findings that contradicted the prevailing practice of doctors were ignored.

"The conservative stance toward including women in drug trials that became entrenched in the 1970s as a result of these experiences," writes Carol Levine in the Journal of Evaluation Review, "was reinforced by the litigation that followed disclosures of harm. Pharmaceutical companies concluded that one way to avoid liability claims was to exclude women from research, even though the claims against them were based on injuries incurred when physicians used the drug in medical practice, rather than in research studies."

The result has been a big chill in research. Researchers now realize that they not only have to consider a woman's changing hormones and whether a drug would affect her unborn baby, but also whether it could affect her childbearing capability and the later health of her children--in the case of DES, 20 years after they're born.

Contraceptive research, another issue in women's health, is now at a virtual standstill in the United States, and product-liability litigation is also cited as the reason for that. "Liability insurance--covering both the conduct of clinical trials and the use of a finished product--is prohibitively expensive and, in some cases, nearly impossible to obtain," states a recent report from the nonprofit Alan Guttmacher Institute, "Contraceptive Development: Why the Snail's Pace?"

But in a New York Times interview, Roderick MacKenzie, chairman of Gynopharma, a small firm that markets the ParaGard IUD, challenges that conclusion: "The truth of the matter is that the cost of defense, insurance premiums, settlements and court-mandated judgments has not been overwhelming. It represents a very small cost when measured as a percentage of sales over the past 5, 10 or 20 years." MacKenzie adds, however, that researching immunotherapy and cardiovascular drugs is easier and more rewarding: "You don't have to be 100 percent effective, you can be 70 percent effective. Your side effects don't have to be zero, they can be 20 percent and still not be unacceptable. You don't have a sea of bad publicity endangering your other drugs, and your researchers can get Nobel Prizes."

Richard Edgren, director of scientific affairs at Syntex Laboratories, a leading manufacturer of birth-control pills, told the Times that the real reason for the small amount of research being done is that "you can keep four or five researchers busy in the area of reproduction, but you could put the same four or five in cardiovascular research and be likely to come out with a more lucrative product."

Economics is not the only factor slowing down contraceptive research. Politics--both conservative and feminist--have also played their part. Side effects associated with the first generation of birth-control pills (which were reduced when the dosage was adjusted) prompted many feminists to reexamine hormone-based contraceptive methods; and in the 70s they successfully lobbied the FDA to withdraw its approval of Depo-Provera, an injectable contraceptive available in many other countries. Drug companies became convinced, Edgren told the Times, that "after $100 million of work, women can throw it out, even after the FDA has approved it."

The antiabortion lobby has so far kept the new French drug RU 486, which prevents gestation of the embryo, off the U.S. market by threatening to boycott all the manufacturers' other products. Bowing to that pressure, the FDA imposed a strict import ban on RU 486, making it unavailable for research even though the drug has shown promise in the treatment of breast cancer, endometriosis, brain tumors, Cushing's syndrome, and even AIDS. Democratic Congresswoman Pat Schroeder, cochairman of the Congressional Caucus for Women's Issues, points out that antiabortion pressure has also halted other experiments--as in the case of fetal-tissue research on Parkinson's disease. "Doctors want to do research," she says. "They don't want to spend all their time fighting with right-wing cuckoos. I think they're terribly afraid to do any kind of research on women, especially of childbearing age. Because if they find out anything that affects fetuses, here comes the right wing again."

In 1989, out of a $7.6 billion budget, the NIH allocated a mere $8 million to applied contraceptive research development and only $3 million to evaluating contraceptive safety. The NIH doesn't even have an obstetrics and gynecology department, and there are only three ob-gyns there.

It's not as if research isn't needed. The United States has staggering rates of teenage pregnancy and abortion: 95.2 of every 1,000 American girls age 15 to 19 will get pregnant (compared to 13 in the Netherlands); 43.5 will have abortions (compared to 14.2 in Canada). The United States is the only developed country where teenage pregnancy is on the increase. Teen parents and their babies face multiple risks: higher infant death, low birth weight, and seriously disabled babies. Teen mothers now make up over 61 percent of all women receiving Aid to Families With Dependent Children.

A study from the Guttmacher Institute found that "every public dollar spent to provide contraceptive services saves an average of $4.40 in funds that would otherwise have to be spent to provide medical care, welfare and other social services to women, who by law would be eligible for such services if they became pregnant." The same study also reports that government funding for family-planning services has declined since 1980. Yet U.S. women have far fewer contraceptive choices than their European counterparts, and that's unlikely to change. When Norplant--a small surgical implant that blocks conception, approved for use in 12 other countries--was introduced in the United States in December, it was the first contraceptive to be approved by the FDA in 25 years. Whereas in the early 70s eight major pharmaceutical companies were conducting contraceptive research, today there's only one.

The watershed women's health issue has been AIDS. Women are now the fastest-growing group infected with the HIV virus, as Robert McClory reported in the Reader last February in "Women and Children Last," and AIDS has become the number-one killer of black women in New York and New Jersey. However, because AIDS was initially perceived as a disease affecting gay men or intravenous drug users, the majority of whom are men, government-run AIDS clinical trials have enrolled only 5 percent women. The original studies on AZT (the only government-approved AIDS drug) included only 13 women among 282 patients. Recent laboratory studies on female mice at University Hospital in New Jersey now indicate that AZT may cause vaginal cancer.

"Efforts to include women in HIV/AIDS drug trials confront several barriers," writes Carol Levine in the Evaluation Review journal. One barrier is "the regulatory system, which has considered women of child-bearing potential and their actual or potential fetuses as vulnerable subjects in need of special protection against risk." Another is "the pharmaceutical industry, which, by excluding women from drug trials, seeks to avoid potential liability for the possible teratogenic effects of experimental compounds." Women also may be excluded because they are drug users and presumed to be noncompliant, because they are members of minority groups who lack access to the health-care system and research institutions, or because "most of the trials so far have focused on AIDS itself, and many of the women have been infected [with HIV] recently and have not developed a clinical diagnosis of AIDS."

The definition of AIDS put out by the U.S. Centers for Disease Control is based on symptoms that appear in men. In fact women often manifest different symptoms, such as severe fallopian-tube infections, pelvic inflammatory disease, vaginal infections, and cervical cancer. The result, according to ACT UP/LA's Women's Caucus, is that women are often incorrectly diagnosed, and that means they're not eligible for AIDS drugs, participation in clinical trials, medicaid, medicare, social security benefits, and a variety of other services available to those diagnosed with AIDS. For all these reasons, ACT UP says, the average woman with AIDS survives 15 and a half weeks from diagnosis to death; the average gay white man survives 30 months.

The AIDS epidemic has arguably recast the ethics of research on human subjects--suggesting that the right to be a subject may supersede the right not to be. It has also mobilized a broad and persuasive political movement seeking to bring about fundamental changes in the way science operates. "The debate has been driven by the articulate demands of those most threatened by AIDS," writes Ronald Bayer of Columbia University in the Evaluation Review. "Rather than the careful exchange of academic arguments, we have been witness to the mobilization of disruptive and effective political protest."

Experts on AIDS and on women's health have been meeting throughout the past year to put pressure on the medical establishment to revise its research and health-care priorities. The Congressional Caucus for Women's Issues has been putting the heat on the NIH about the way women fit into its research agenda. The NIH spends only 13.5 percent of its budget on studies related to women's health issues. Just what are women getting for their tax dollars?

Last summer the caucus introduced the bipartisan Women's Health Equity Act, a package of 20 individual bills providing for increased research on a wide range of women's health issues. It would increase funding for studies of breast cancer (cases of which increased 32 percent between 1982 and 1987, and which will kill roughly 44,000 this year), contraceptive and infertility studies, and research on women and AIDS and on osteoporosis (which kills more women than breast cancer); it would also fund service and treatment programs. During its last session, Congress passed 2 of the 20 individual bills: one providing increased access to breast- and cervical-cancer prevention for low-income women, the other allowing medicare to reimburse mammography costs for women over 65. Perhaps most important, the act includes bills addressing the fundamental reason women receive second-rate health care in America: inequitable research.

In 1989 the caucus asked the General Accounting Office to audit the NIH and tally up how many studies with research grants had received a waiver to exclude women (a 1986 NIH policy encouraged the inclusion of women unless there is a "clear" reason not to) and how many included only one gender; it also asked whether studies were being designed to detect differences in how treatments affect men and women. It wasn't the first time the NIH had been called to account. In 1985 a Public Health Service task force had criticized the NIH for its failure to research women's health problems, saying that "the need for data that are relevant to health and that are sex- and age-specific by race and ethnicity is crucial." The response was the policy encouraging the inclusion of women in clinical-study populations.

The GAO report, delivered last summer, concluded that the NIH had made little progress since 1986. The policy had not been consistently applied until 1990, and then only to research outside the NIH; the NIH had not even revised its grant-application booklet to communicate the policy to the research community. Nor was the NIH considering the inclusion of women as a key factor in determining a research proposal's merit. It wasn't even keeping data on the demographics of study populations, as it had been advised to do by the 1985 task force--despite the fact that in the GAO report the NIH admitted that underrepresentation of women in studies "has resulted in significant gaps in knowledge."

"The NIH has been inexcusably slow in addressing the practice of male-only research," says U.S. Representative Olympia Snowe, cochairman of the women's caucus. "The research community and the NIH's attitude has been able to consider more than half the population as some sort of special case."

Following the critical GAO report, the NIH hastily set up an Office of Research on Women's Health, and appointed Ruth Kirchstein, who also works as director of the National Institute of General Medical Sciences, its acting director. (Kirchstein had headed the Public Health Service task force that criticized the NIH in 1985.) Last September, acting NIH director William Raub announced that the NIH would seek new funds for fiscal year 1992 that would be appropriated for "new or expanded research initiatives aimed at issues related to women's health." In March, Dr. Bernadine Healy was confirmed as the first woman to head the NIH. She has been quoted as saying that "relentless pressure" must be applied to policymakers and researchers to ensure that women are equally represented in health studies. Shortly after her confirmation she announced a ten-year study of the major causes of death among women--cancer, heart disease, stroke, and osteoporosis. The study, she said, would involve hundreds of thousands of women and cost as much as $500 million.

Raub assured the Congressional Caucus on Women's Issues last September that the NIH would "take whatever steps are necessary to ensure that appropriate numbers of women are included in research projects." He said the NIH's grant-application booklet would be revised to state clearly that adequate numbers of women must be included in trials, that failure to include women would adversely affect a research proposal's rating, and that any reasons for not including women must be "compelling."

In response to the charge that last year the NIH spent just 13.5 percent of its budget researching women's health, Kirchstein said: "This does not mean that 86.5 percent is spent on diseases of men. Rather, the vast majority of NIH research funds devoted to clinical studies are expended for studies of diseases which affect both men and women." Raub estimated that the NIH "devoted about 5 percent of its budget to research on health issues pertaining primarily or exclusively to men."

Schroeder points out that the 13.5 percent figure came from an internal NIH report, prepared by the NIH Advisory Committee on Women's Health Issues. "We certainly understand that the 13.5 percent figure doesn't mean that 86.5 percent of NIH funds are expended on research on men," she says. "However, the fact is that women have been excluded from many of the research studies affecting both genders, and even when women have been included in these studies, the discovery of gender differences in disease development or treatment often does not lead to further research on the special risks facing women."

Whether this time around the NIH will make good on its commitment to women is uncertain. "We first spoke with the NIH early in the 80s, when we began hearing complaints from women researchers," says Schroeder, "and the NIH was very compliant. They said there wasn't any need for legislation, that they would correct inequities voluntarily. But then everyone said nothing had changed. When the GAO report proved it, we had to declare war." Schroeder and Snowe are quick to connect the NIH's indifference to women's health with the fact that women scientists are underrepresented in decision-making positions. A 1986 GAO report found that the NIH had not complied with the Equal Employment Opportunity Commission's affirmative-action requirements, and had been particularly slow in resolving EEOC complaints. The 1985 Public Health Service task force had also recommended that the NIH "increase the number of women in key positions in health practice, administration, research and education as rapidly as possible."

Self Help for Equal Rights (SHER), an organization formed in 1972 to address the issue of sex discrimination at the NIH, maintains statistics on the status of women there. These show very few women in the upper civil-service grades, a situation that's changed little according to surveys completed in 1976, 1984, 1988, and 1990. Billie Mackie, president of SHER, said at a press conference last December that in 1990 "the senior executive-service positions are almost all occupied by white males."

In December Schroeder and Snowe asked Health and Human Services Secretary Louis Sullivan for specific information on the career status of men and women researchers at the NIH, as well as at the FDA and at the Alcohol, Drug Abuse and Mental Health Administration (ADAMHA), which oversees the National Institute of Mental Health. They asked for the length of time researchers had been at the institute, whether they had achieved tenure, the dates of most recent promotions, and current grades and salaries. They also sent a letter to President Bush reiterating their hope that more women would be appointed to policy-making positions, particularly in science and technology, and noting that of the 60 top positions in science and technology identified by the Council for Excellence in Government, only 6 are filled by women.

According to a 1990 AMA report, women still make up just 17 percent of the physician population in this country--though that is a 92 percent increase over the last decade. But significantly, almost 40 percent of all medical students are now female. The AMA projects that by the year 2010, almost a third of all physicians will be women. Interestingly, though the AMA has long been considered one of our most politically conservative professional organizations, it seems to be exhibiting an unusual sensitivity toward women, who are well represented in its governing body, the House of Delegates.

"A couple of years ago the AMA decided to make a real effort to begin stamping out discrimination," says Dr. Dorothy Starr, one of those delegates. "And because of the increased presence of women in the AMA, there is more consideration of women's issues." Among the AMA's recent efforts is the report "Gender Disparities in Clinical Decision-Making," which cites data suggesting "that a patient's sex plays an inappropriate role in medical decision-making. . . . For instance, there is evidence that physicians are more likely to perceive women's maladies than men's as the result of emotionality." The report concludes that there should be more medical research on women's health and health problems, that the results of research done on males should not be generalized to females without evidence that the results apply equally, and that research on general health problems should include male and female subjects. It also urged physicians to "examine their practices and attitudes for the influence of social or cultural biases."

"It isn't that people mean to discriminate," Dr. Starr says of the situation at the NIH. "It's just that they don't think about it. In the AMA there are enough women that we are able to meet regularly about our concerns, and it's been really helpful. At the NIH there aren't even enough women to caucus."

"We do need a critical mass to be heard and be felt," says NIH health science administrator Fann Harding. "And the reason that we're suddenly hearing about these issues is because now there is a critical mass of women in Congress, and we've got their help."

In her 1984 book Science and Gender, the late Dr. Ruth Bleier argued that science, like all of Western culture, reflects a consistent patriarchal bias. That bias, according to microbiologist Viola Young-Horvath, head of the Federation of Organizations for Professional Women, helps to explain why the NIH "has continued to be as it was in the 1970s when I was employed there--a predominantly male enclave at the higher levels, full of men who are intellectually unquestioning of their own behavior and decisions."

Because scientific methods can be manipulated to support expectations, the very questions scientists ask often suggest certain responses. "As social movements threaten the social order," says Bleier, "scientific theories emerge that implicitly defend the status quo." Bleier, who was a professor in the Neurophysiology Department and Women's Studies Program at the University of Wisconsin in Madison, points to the rise of biological-determinist theories--popular with the American right--as a response to feminist scholarship and the women's movement. There's a historical precedent in the 19th-century "science" of craniology, used to explain the "inferiority" of women and blacks. Today's equivalent, says Bleier, is Wilsonian sociobiology (named after Harvard's E.O. Wilson), which posits that class struggles, war, and racism are the inevitable results of evolutionary adaptations based in our genes, and that the social roles played by men and women are also biologically and genetically determined--theories used by both Britain's neo-fascist National Front and France's extreme right.

The medical establishment has flip-flopped even on the role played by biology in women's lives. "In the past, differences between men and women were ascribed to biology," says Dr. Ramey, past president of the Association of Women in Science. "And these differences were then cited to exclude women from positions of responsibility. But now we see a very interesting thing. Male scientists, who are typically in charge of laboratories and research and put only men in their studies, now claim that is acceptable because men and women are the same." Women's relation to science--excluded from clinical trials and largely absent from the NIH--simply mirrors women's traditional role in the rest of our culture. "Science epitomizes the structure and history of Western civilization," says Bleier. However, sexism in science has implications that go beyond job discrimination. "In my laboratory I make it a point to have researchers of different ethnic and racial backgrounds, and of both genders," says Dr. Ramey. "When you include only men, what you really have done is to exclude a major source of possibilities for different solutions."

The debate over the state of women's health care has begun to change ideas about research, and this new vision is radically pluralistic. Bleier, for instance, says that there may be "no single 'correct' explanation, no simple, dramatic 'cause'" for a given medical phenomenon. She suggests that a researcher's history, knowledge, and particular expertise may bring to a study an inclusiveness and a context that will reveal more aspects of a phenomenon. "Together we illuminate many different facets," she says, "all varied aspects of the truth."

Bleier's vision of a new scholarship is echoed by Dr. Ellen McGrath, chairman of the American Psychological Association's National Task Force on Women and Depression, which found that women tend to be more depressed than men primarily because of the difficulties of "being female in contemporary culture." The task force claimed that, to understand women's depression, women must be studied in a "biopsychosocial context," McGrath says. "This means we must understand how women's biology interacts with their environment, and when "biology' is a social construction rather than a woman's physical reality." Taking a biopsychosocial approach would show how gender differences have been denied in mental-health research and practice. Increasing evidence suggests, for instance, that men and women respond differently to certain antidepressants, and possibly to certain psychotherapies.

Columbia University's Ronald Bayer also calls for a new approach to medical research. In a 1990 Evaluation Review article, he writes about how community-based AIDS research, which designs and conducts its own trials sponsored by pharmaceutical companies and utilizing a pool of private physicians, has successfully circumvented the NIH.

Community-based researchers focus on strategies to manage the opportunistic infections and complications that kill people with AIDS. Whenever possible, they test such strategies in the real world--evaluating drugs in relation to different nutritional regimens, for example, or including populations heavily affected by the disease but rarely used as research subjects: IV drug users, African Americans and other ethnic minorities, prisoners, and women. "[Reformers] have demanded a basic reconceptualization of the relationship between researcher and subject," Bayer writes. "In place of protocols imposed from above, they have proposed a more egalitarian and democratic model in which negotiation replaces scientific authority."

Bleier hopes that a feminist view of science might change it radically: "What is potentially and ultimately revolutionary in the feminist critique is that the patriarchal structure of science, its theory and practice, will not be left intact. What is developing as a unique emphasis in feminist scholarship is the value of and the necessity for the plurality of our views."

According to Dr. Nancy Kreuger, a biomedical researcher for Kaiser Permanente, a huge HMO, the debate over women's health care has reached a critical point: "The women's movement has finally put enough women--and their point of view--into science and medicine. And we have benefited, tragically, from the experience of AIDS--it has increased our consciousness of the politics of the budget-making process and of what gets researched and what gets ignored. Science, we're now seeing, has not been an entirely objective affair."

Research assistance provided by Mary Melton

Art accompanying story in printed newspaper (not available in this archive): illustration/Archer Prewitt.

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