Easing Hormone Anxiety

Five years ago panicked postmenopausal women threw away their hor­mone, pills after the federal government revealed that the drugs raised the risk of breast cancer and coronary disease. In 2006 only six million U.S. women got hormone prescriptions, a dramatic drop from 16 million in 2001. It seemed like the end for hormone therapy, especially for the previously fashionable notion that hormones protected older women from cardiovascular disease and other ills caused by aging.

But papers published this year, written by researchers who delivered the original warning, show that taking hormones soon after menopause—within about 10 years— is safe for most women. The data even suggest that hormone therapy for less than 10 years may improve some women's health more than doing nothing.

The uproar over hormone therapy began in July 2002, when researchers asso­ciated with the massive Women's Health Initiative (WHI) reported on one section that was following nearly 17,000 partici­pants. Women taking a specific combina­tion of estrogens and synthetic progester­one, they said, were experiencing small in­creases in breast cancer. WHI investigators also found bump-ups in stroke, pulmonary embolism and coronary heart-.dis­ease. The National Institutes of Health, which runs the WHI, sent warning letters to study subjects and abruptly shut down the trial. (Epidemiology studies reported this year have observed a drop in breast cancer rates since the trial ended, although some evidence suggests that the slide actu­ally began before the termination.)

In 2004, however, the outlook for hor­mones began to improve. The WHI pub­lished new clinical trial data on hysterecto­mized women who took only estrogen. (Be­cause estrogen can promote uterine cancer, women who have uteruses often also take some form of progesterone, which protects against the disease.) The estrogen trial also stopped early, this time because of slight stroke increases. But startlingly, these women suffered fewer heart attacks, and even less breast cancer, than women taking a placebo. Among 3,310 women ages 50 to 59 divided roughly equally between estro­gen and placebo groups, 16 estrogen users developed coronary heart disease, com­pared with 29 in the placebo group; 35 pla­cebo users developed breast cancer, com­pared with just 25 in the estrogen group.

That age strongly affects the outcomes received confirmation earlier this year, when WHI researchers reanalyzed their original data and combined them with the

estrogen numbers. Besides generally veri­fying the decreased risk in heart disease, they also show that the re­sponse to hormone ther­apy depends on a woman's age and years since meno­pause. Even the inevitable rise in stroke and blood clots was less in younger women (those younger than 70). Women in their 70s, however, suffered similar heart disease rates whether they took estrogen or a placebo.

In looking back at the fallout from the 2002 report, Jacques Rossouw, who heads the WHI trials, acknowledges that women younger than 60 who would have been appropriate candidates for hormone therapy—those suffering severe hot flash­es, for instance—fled from hormones along with older women. "My surmise is that women just got scared of hormone therapy across the board, irrespective of what they were using it for," he says. "With hindsight you could say, well, maybe we should have emphasized reasonable use even more." The study's abrupt termination may have also stoked fears. "Maybe we didn't need to do it that way," remarks WHI investiga­tor Marcia Stefanick of Stanford Univer­sity. "It wasn't an emergency—it wasn't like people were, you know, under serious threat of the adverse outcomes."

Wulf Utian, executive director of the North American Menopause Society, crit­icizes the WHI researchers because, as he puts it, "they've always taken the glass-half-empty read on their data." Utian also says that, especially between 2002 and 2004, declarations made in press releases or interviews were much more negative than the conclusions in published scientif­ic papers. The data seemed particularly alarming because the risks often appeared in relative terms, such as a 29 percent in­crease for heart attacks between hormone users and nonusers, rather than in terms of total risk, in which the overall heart attack risk rose by just 0.07 percent, from 33 to 40 per 10,000 women per year.

JoAnn Manson, a WHI investigator at Harvard University, says that in 2002, anal­yses on years since menopause had not yet been done, and it took the 2004 estrogen-only results to make clear that younger women were at much less risk. Still, she notes, strong hints of an age effect in earlier clinical and ani­mal studies existed: "Taking all of the previous research into account, there may have been a reason to look very closely at differences by age and differ­ences by time since menopause." Had that been part of the earliest reports, Manson remarks, it might have helped put the re­sults into perspective for younger women. Overall, WHI researchers say they are pleased to have derailed the trend of prescribing hormones for women long past menopause.  Still, Stefanick says, "I wish we had figured out a way to change prescribing practices but have fewer people distressed about it."