The new report is based on previously published studies, not new findings. But it has forced countless women to revisit a familiar question–will estrogen prolong my youth or hasten my death? –and left many feeling whipsawed. “This is a good time for those who have believed in estrogen’s benefits to take a second look,” says Dr. Steven Cummings of the University of California, San Francisco, “a time for women who are taking estrogen to ask themselves and their doctors why.” It’s still impossible to tally the risks and payoffs with precision, but experts have reached a broad consensus about HRT. Most now endorse estrogen as a short-term remedy for hot flashes and other acute symptoms. But few see any reason to continue treatment for more than five years.
Why the new consensus? Until recently, expert opinion was based almost entirely on “observational” studies. Unlike controlled clinical trials–in which researchers randomly assign volunteers to receive a treatment or a placebo and then compare outcomes–observational studies simply plot disease patterns among different groups of people. When the American College of Physicians issued its then-definitive HRT guidelines in 1992, observational studies had repeatedly found that long-term estrogen users suffered elevated breast-cancer rates but enjoyed lower-than-average heart-attack rates. The heart benefits appeared far greater than the breast risks, so the experts embraced estrogen as a boon to women’s health. “We thought most postmenopausal women should take HRT unless they were already at high risk of breast cancer,” recalls Dr. Deborah Grady of UCSF, who led the 1992 review.
Unfortunately, no one knew whether estrogen was really protecting people’s hearts. If women on HRT were more health conscious in general (a reasonable inference), could lifestyle account for their low rates of cardiovascular disease? To address that question, Wyeth (the maker of Premarin) sponsored a large clinical trial called HERS during the mid-1990s. In that study, some 2,800 volunteers with known heart disease took either estrogen or a placebo for four years. The women on HRT saw their cholesterol levels improve, but they suffered an increase in blood clots and no reduction in heart disease (their heart-attack rate spiked during the first year but leveled off later in the study). It’s possible that the estrogen users, with their lower cholesterol, would eventually have come out ahead–or that they would have reaped greater benefits had they started treatment earlier. To settle those questions, the National Institutes of Health is now tracking 27,000 women who started various regimens (including estrogen) while still in good health. Findings from this larger “Women’s Health Initiative” are due out in 2006. But on the strength of today’s evidence, experts are no longer championing estrogen as heart medicine. As Grady points out, the cholesterol-lowering statin drugs are a safe, proven alternative.
What about the bones? There’s no question that estrogen can slow the rapid bone loss that sets in with menopause. But clinical trials have yet to show conclusively that HRT prevents spine and hip fractures. When researchers pooled results from several relevant studies, they found hints that estrogen may reduce fractures by 25 percent to 30 percent, at least among women under 60. But there are surer ways to reap that benefit. Raloxifene, an estrogen alternative introduced by Eli Lilly in 1997 under the brand name Evista, reduces the risk not only of fractures but of breast cancer. And the nonhormonal bone boosters Fosamax and Actonel reliably cut fractures by 40 percent to 50 percent.
Premarin may never regain its status as an all-purpose rejuvenator, but don’t expect it to vanish from the market. There is still no evidence that women using estrogen for five years or less raise their breast-cancer risk. And no one has found a better short-term remedy for the hot flashes, night sweats and insomnia that menopause can cause. “If a woman is having disturbed sleep and impaired quality of life,” says Dr. JoAnn Manson of Harvard Medical School and Brigham and Women’s Hospital, “the benefits are likely to outweigh the risks. We don’t want to discourage short-term HRT.” Alas, estrogen relieves symptoms only as long as you take it; they can return with a vengeance when you stop. How short does “short-term” need to be? The Women’s Health Initiative should yield clearer answers in 2006. Stay tuned.
