HEALTHMaturing of women's health: The success of a decade-long clinical test projectThe Women's Health Initiative was launched in 1991 in an effort to gain insight into the health issues faced by older women. It has achieved much more.By Victoria Stagg Elliott, amednews staff. Dec. 2, 2002. In 1991, Susan Hendrix, DO, associate professor of obstetrics and gynecology at Wayne State University School of Medicine in Detroit, received the offer: Would she like to be her institution's principal investigator for the Women's Health Initiative? She jumped at the chance. At the time, naysayers asked her why she was bothering. Hormone replacement therapy was obviously good for women. And why mess with a randomized clinical trial so large it appeared undoable? But she had her reasons. "I was a woman aging, and I wanted answers," said Dr. Hendrix, who turned 50 last month, bringing her within the age range of the study group. "This was different from anything that came before it because it was the kind of study that should change clinical practice." Since its inception, the National Institutes of Health-sponsored WHI has done exactly that. This multicenter study with more than 160,000 female participants has not only changed how women fit into the medical research enterprise, but also challenged conventional wisdom.
More than 160,000 females have participated in the Women's Health Initiative.
Last summer's announcement regarding the risks of HRT -- one of the initiative's study arms -- is a powerful example. But this is only one aspect of the WHI, and those involved in the continuing research say the emerging body of knowledge will have a place in the exam room for a long time to come. When Bernadine Healy, MD, the first female director of the National Institutes of Health, launched the WHI in 1991, clinical trial experts said it couldn't be done -- that recruiting such a large number of women to participate in the study was impossible. Women weren't interested in clinical trials. And even if they did sign up, they weren't likely to follow through. The doubts were widespread. "They said you couldn't get [women] to do it," said Howard Judd, MD, principal investigator of the WHI at University of California, Los Angeles. "They're too flighty and flaky. It was just utter nonsense. And no one was interested in researching older women. For many researchers, if women were interesting, it was because they were young and attractive." And there were other arguments against it. A study this large and comprehensive was too expensive. Couldn't smaller, cheaper trials achieve the same results? And besides, what could possibly be learned that couldn't be learned from men? "Men were the normative standard," said Dr. Healy, a cardiologist. "At the time, women's research was reproductive. It did not look at her total health. Being a woman, aside from the reproductive tract, was the same as being a man. When a women's reproductive tract shut down after menopause, she wasn't really a woman anymore. She was a man." Meanwhile, HRT had already been in use for nearly 50 years. Smaller, observational studies had suggested that it was protective to the cardiovascular system. It had already been proven that it was good for the bones, and many suspected it lowered the risk of some cancers. Since HRT was considered to be so good for women, wasn't it unethical to put some on placebo? "Many thought the heart hypothesis was a slam dunk," Dr. Healy said. "There was almost a mind-set that you should put hormones in women's drinking water." Against all oddsEven the Institute of Medicine questioned WHI's value. An IOM report released in 1993 found that smaller trials looking at specific health issues rather than one, big expensive trial examining all of them would probably make more economic sense and find more answers. It should have been the end of the WHI, but it wasn't.
Hormone replacement therapy has been in use for almost 50 years.
"That [IOM report] could have shut us down, but the grants had been issued and the study had been started. It couldn't be stopped," Dr. Healy said. "And if the WHI had not been done at that point in time, it never could have." The NIH, long criticized for shortchanging women's health, already had designated 40 centers nationwide to recruit the necessary number of women for the initiative's various arms. The agency also was ready with $625 million to pay for it. "At the time, there wasn't much practical, clinical-based work, and the basic science wasn't there," Dr. Healy said. "The notion of worrying about gender just wasn't a concept." But the project's vision emerged: It would focus on preventing the most common causes of disability in older women -- breast and colorectal cancer, heart disease and osteoporosis. The most notorious arm of the study randomized thousands of women to receive either a form of hormone replacement therapy or placebo. Another required women to stick to low-fat, high-fiber diets to determine the impact on breast and colorectal cancer. A third randomized women to receive calcium and vitamin D pills or placebo to determine the impact of these supplements on osteoporosis-related fractures and colorectal cancer. Additionally, the project's observational component would track various health risk factors. "The observational study has not even yet begun to flower," Dr. Healy said. "I said we needed a Framingham for women. This is bigger than that." In the 10 years since, the impact has been tremendous. For starters, the July 9 suspension of the WHI arm studying combined progestin and estrogen therapy created a firestorm in the women's health community because the arm was finding scientific evidence to offer doubt about what before had been considered optimal treatment. "We used to think that you could take one magic bullet that would fix all of a woman's problems for the rest of her life, and now we know that you can't," Dr. Hendrix said. "I wanted answers, and I'm glad I got some." But beyond this finding -- and the splash it created in the news and in the lives of women and their doctors -- the study has quietly achieved much more. "Over a decade, it has catalyzed women's health research and become a movement," Dr. Healy said. "It institutionalized it and mobilized hundreds, possibly thousands of investigators, focusing on critically important issues for women's health and beyond." Many women's health experts say the study has raised the bar for the level of evidence required before therapies or treatments will be recommended on a wide scale. And observational studies or clinical trials that include only Caucasian men are no longer good enough. Women will never again be just little men. "It will make us all more cautious about making claims before we do enough good quality research to prove the point," said Judy Norsigian, executive director of the Boston Women's Health Book Collective, a women's health advocacy group, and co-author of Our Bodies, Ourselves. The study also destroyed the myth that women were not interested in clinical trials. Many centers not only made their recruitment deadlines, they beat them. The study also attracted large numbers of ethnic minorities who had also traditionally been underrepresented in research. Experts say the WHI has gone a long way to address the knowledge gap, well beyond the specific questions asked by the study. The WHI has created an infrastructure of women's health data that is now being used for hundreds of spin-off studies. Blood has been banked and is being used in genetic and biological marker tests that hadn't been imagined when the study began. Now, researchers and institutions are in place to utilize these resources. "It's a gold mine to test all sorts of hypotheses with regard to the health of postmenopausal women," said Maurizio Trevisan, MD, chair of the Dept. of Social and Preventive Medicine at the State University of New York at Buffalo and WHI principal investigator at the university. Although the study was so expensive that its large-scale replication is unlikely, its multifactorial approach -- rather than single-disease emphasis -- will probably be incorporated in future studies. It also expanded the way researchers focus on prevention, looking beyond medicines to include lifestyle and environmental factors, Norsigian said. Women's health researchers also said the WHI made their jobs easier. Menopause is now an area of legitimate scientific inquiry. Projects are easier to get off the ground. No one questions whether women can be recruited for clinical trials. And the previous critical reviews of NIH policies and efforts to include women in trials have turned to praise. "There's been such a sea change," Norsigian said. "We've really come a long way." Miles traveled, but miles still to goAlthough everyone says great strides have been made, most agree more progress is needed. For instance, though women are now included in clinical trials, the numbers are not always enough to draw conclusions about the impact of gender on drug efficacy and safety. The quandary remains how to do so without significantly raising trial costs. "The difficulty we face is that when we study multiple populations, not only sex, but different ethnic groups, we face the need to enroll very large numbers of people to find questions specific to their individuality," Dr. Hendrix said. "If you have a drug and you want to test it in all different populations, then it becomes extraordinarily expensive. "I think what we're all struggling with is how to answer the questions, make them generalizeable to all people, not just the subset, but at the same time not drain our financial ability to do studies," Dr. Hendrix said. Although the WHI went a long way to address the inequities in women's health research, it's only the beginning. "There's an immense amount of work to be done," said Dr. Judd, who also serves as vice chair of the Obstetrics and Gynecology Dept. at the University of California, Los Angeles. "I'm just so thrilled we got this one study. To do this correctly was so important." ADDITIONAL INFORMATION:WHI timeline1942: Food and Drug Administration approves hormone replacement therapy for the treatment of menopausal symptoms.
One patient's view: Why I joined WHITwelve years ago, Anne Tanner, a 63-year-old publications editor at the University of Iowa in Iowa City, went to her physician to talk about menopause. What she heard made her angry. "My doctor told me that not very much was known [about women's health]. The research had been on 55-year-old males, and it was becoming evident that we weren't the same and that we just would not be able to get any useful information on what was happening," she said. "I was absolutely furious. Not with the doctor, just with medical life in general." So when flyers started appearing on bulletin boards and advertisements showed up in the local paper asking women to sign up for a large study researching factors influencing the health of older women, Tanner didn't hesitate to call. "I wanted to make a contribution to medical science so that my daughters, granddaughters and nieces would have more information," she said. But Tanner has gotten more out of the study than just the satisfaction of contributing to the body of knowledge about the health of older women. The study itself has also prompted her to make significant changes in her life. She has been involved in both the HRT arm of the Women's Health Initiative as well as studies exploring the value of low-fat, high-fiber diets and vitamin D and calcium supplementation. "I'm allowed 24 grams of fat or fewer per day. It's been a big commitment to change my diet, but once you get into it, it's fascinating, because you don't want the foods that have a great deal of fat," Tanner said. "I learned an enormous amount." WeblinkNIH Women's Health Initiative (http://www.nhlbi.nih.gov/whi/) Article, "Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women," Journal of the American Medical Association, July 17 (vol. 288, issue 3) (http://jama.ama-assn.org/issues/v288n3/ffull/joc21036.html) Report, Assessment of the NIH Women's Health Initiative, IOM, 1993 (http://www.nap.edu/catalog/2271.html) Copyright 2002 American Medical Association. All rights reserved.
|
Featured stories     
« Prev
1
2
3
4
5
6
Next »
Current topicsMost-viewed
This weekDoctors zero in on benefit gaps allowed under health reform Hot-button issues drive state CME mandates Get our email alertsUse our one-step registration. Learn more Your information will not be shared. Privacy policyColumns and series
From the vaultQuotable"The federal government has never given a free pass to produce and consume marijuana, even for medical purposes." U.S. District Court Judge for the District of Montana Donald W. Molloy, ruling that the state's law legalizing medical marijuana doesn't protect distributors from federal prosecution |
|||||||||
SHARE
