For the Young at Heart
In 2002, The Women's Health Initiative put forth a real shocker: Commonly prescribed post-menopausal hormone therapy increased heart attacks. Overnight, the news debunked the entrenched notion that virtually all women should be taking HT for the rest of their lives. Last week, performing a new analysis on the reams of data collected on the 27,347 women in the scientific trials, investigators reporting in the Journal of the American Medical Association found that the cardiac risk of HT rises the further a woman gets from menopause. And, for the group of women who started hormones in their 50s, estrogen, as opposed to the combination of estrogen plus progestin (Prempro), brought no heart risk and maybe even some benefit. One might groan at this seeming flip-flop, but in fact this is an important clarification that should help women make better personal decisions.
For at least 20 years, the data on the relationship between female hormones and their hearts have been maddening. In 1985, the Nurses' Health Study showed that women who used post-menopausal hormones had a 50 percent reduced risk of heart attack compared with those who did not use them. But in the very same issue of the New England Journal of Medicine, the venerable Framingham study (famed for identifying cardiovascular risk factors like age, high blood pressure, and smoking) found that women from 50 to 83 years of age who took estrogen had a 50 percent increased incidence of heart disease, particularly the smokers. The Framingham investigators warned of HT's widespread use. But estrogen soon became a darling of preventive medicine as further observational studies reinforced the positive findings of the nurses' study.
Over the next decade, prominent professional medical groups recommended hormones for heart protection. With this presumed lifesaving advice in hand, doctors set out to persuade often reluctant women to take hormones, regardless of age. In this environment, it was tough sledding getting the WHI off the ground (as director of the National Institutes of Health at the time, that's when I noticed my first gray hair). Hoping to mirror the millions of women who were actually taking hormones, the trial by design included almost 9,000 women in their 50s, but also thousands of women in their 60s and 70s. But even as the WHI trials were proceeding, the Institute of Medicine criticized them for tackling the heart-hormone question at all. The reason: It predicted the cardio-protective effects would be a slam dunk, eventually forcing the studies to be stopped early.
But there were nagging concerns that shadowed medicine's love affair with hormones. Prime among them was the so-called healthy user effect. Did the heart benefit seen in the observational studies reflect the hormones, or more the nature of the women taking them, who were generally health conscious, exercised, controlled their weight and blood pressure, and were less apt to smoke?
Yes or no. As Jacques Rossouw, chief of the WHI branch at the NIH, points out, the first heart question about hormones-are they right for all women?-got a resounding "No." Had the answer been "Yes," as most expected, there would be little reason for further analysis. With a no, however, a second question naturally arises: Is it OK for some women? This new analysis tells us these hormones have no or very little risk for women when started within 10 years of menopause. That's reassuring, as it's the time when short-term HT is called upon to relieve menopausal symptoms. But for women years after menopause or with a heavy dose of heart risk factors, hormone therapy should be avoided.
WHI also explains that women are not the same, and neither are the hormones they take, or when they start and stop them. The benefit of HT in the earlier observational studies reflects a combination of a healthy user effect, treatment started closer to menopause, and the choice of hormone-which was mostly estrogen. This all starts to make sense: Among women who have normal coronary arteries, estrogen offers little or no cardiac risk, and its beneficial effects on the lining of the blood vessels and cholesterol levels may help keep them that way for a while. But when there is coronary disease, which can percolate silently and increases with age, particularly among those with heart risk factors, estrogen's tendency to increase inflammation and blood clotting turns a benefit or a neutral into a risk for coronary thrombosis. These are differences that are important for women to understand, and for scientists to pursue.
This story appears in the April 16, 2007 print edition of U.S. News & World Report.