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WOMEN'S HEALTH
Curtain Drawn on Hormone Therapy for Older WomenEstrogen-only Trial in Women's Health Initiative Spotlights Increased Risk of StrokeThe jury is in: hormone therapy is not a good thing for preventing cardiovascular disease--at least in women 60 and older. The verdict is confirmed in the details of the estrogen-only arm of the Women's Health Initiative, published this month in the Journal of the American Medical Association, six weeks after the trial was halted early due to a slight extra risk of stroke. Deliberation continues on possible benefits in younger populations.
For women age 60 and older, the risks of hormone therapy outweigh the benefits, says JoAnn Manson. (Photo by Leah Gourley) In some ways, the latest news was somewhat better than expected. Postmenopausal women without a uterus took the single hormone therapy for an average of nearly seven years without inviting extra heart attacks and with a surprising possible reduction in breast cancer risk. This contrasts with the other arm of the initiative, which was stopped prematurely two years ago after healthy postmenopausal women with a uterus showed an increased risk of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, and dementia after only about five years on the popular combination pill of estrogen plus progestin. These risks appeared to outweigh the benefits of reduced rates of both hip fractures and colon cancer. The news announcement ending the estrogen-only study also suggested a reduced risk of fracture and an increased risk of dementia, but the cognitive function data have not yet been published. Age, Risks and BenefitsFor older women and their physicians, the results may help to simplify the complex risk-benefit calculus of choosing whether or not to take hormones after menopause."For women in their 60s and 70s, the risks of hormone therapy appear to outweigh the benefits," said JoAnn Manson, a co-author of the April 14 JAMA study and the Elizabeth F. Brigham professor of women's health at HMS and Brigham and Women's. "These hormones should not be used for prevention of cardiovascular disease or other chronic diseases."
These results may be reassuring to the best candidates for hormone therapy. Typically, women who have had hysterectomies, usually in their 50s, are most likely to suffer hot flashes, vaginal dryness, and other related issues, said Isaac Schiff, the Joe Vincent Meigs professor of gynecology at HMS and chief of the Vincent Memorial Obstetrics and Gynecology Service at Massachusetts General Hospital. "Estrogens are marvelous for symptom relief," he said, "but I don't prescribe them to prevent heart disease." Schiff chairs a task force of the American College of Obstetricians and Gynecologists that is working to update clinical practice recommendations in light of the latest findings. The most current guidelines and information are available at http://acog.org. The new estrogen-only results mark a final stunning reversal of a decades-old effort to market hormone treatment as a way to prevent chronic diseases of aging, especially heart disease. There was a lot of credible evidence to back up those claims. More than 40 observational studies taken together had suggested that hormone therapy protects against heart disease, Manson said, including several reports from the venerated Nurses' Health Study at BWH that she co-authored. "It was becoming a common clinical practice to start women on hormone therapy in their 60s and 70s because of the view that hormones protected the heart and that women at high risk of cardiovascular disease would benefit the most," Manson said. Among other things, estrogen seemed to lower levels of the harmful low-density lipoproteins and raise levels of the helpful high-density lipoproteins. In women, heart disease rates accelerate only after menopause, when they apparently lose the protective effects of estrogen. In the mid-1970s, after several studies tied unopposed estrogen use to four- to eight-fold higher rates of uterine cancer, it became standard practice to add progestin to the prescription for all women who had not had a hysterectomy. But it appeared that progestin might also block some of estrogen's blood lipid benefits. Meanwhile, the higher risk of breast cancer seemed to be well proven. "Estrogens are helpful for osteoporosis, but I prescribe only after the patient is fully aware of the benefits and risks," Schiff said, adding that breast cancer is by far the biggest concern for a 50-year-old woman, who is not as worried about breaking a hip 30 years down the road. An NIH InitiativeThe National Institutes of Health established the Women's Health Initiative in 1991 as a randomized, double-blind, placebo-controlled trial in 40 U.S. clinical centers, including the Boston site headed by Manson. Its aim was to address the questions and controversies of cardiovascular disease, cancer, and osteoporosis in postmenopausal women.Even before preliminary results halted both arms of the trial, the 1998 results of another study, the Heart and Estrogen/progestin Replacement Study (HERS), the first major trial with clinical disease outcomes, surprised everyone, write Stephen Hulley and Deborah Grady of the University of California, San Francisco, in an editorial in the same issue of JAMA. It found an increase in coronary heart disease during the first year and no overall cardiovascular benefit with longer follow-up when estrogen plus progestin treatment was compared with placebo in women with prior coronary disease. The lower heart disease risk in the youngest cohort of the latest estrogen-only trial, however, may provide a clue to the apparent cardiovascular protection reported previously, Manson said. More than 80 percent of the women in the Nurses' Health Study who used hormone therapy started within two years of menopause, usually in their early 50s. "It's very clear that earlier views were oversimplified," Manson said. "It appears that the age at which women start hormone therapy may be a key factor." To follow up on these unanswered questions, Manson is heading one of eight study centers in a new five-year, privately funded randomized, controlled, double-blind trial of 720 women to figure out the risks and benefits of early estrogen therapy delivered either through skin patches or by pill and with a low dose of vaginal progesterone gel. The study, funded by the Kronos Longevity Research Institute, will use several noninvasive imaging techniques to measure atherosclerosis, the major cause of heart attacks. --Carol Cruzan Morton |
