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Estrogen Therapy and Early Atherosclerosis
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Source: Manson JE, et al. Estrogen Therapy and Coronary-Artery Calcification. N Engl J Med 2007;356;2591-2602.
Despite encouraging animal studies and human observational studies such as the Nurses Health Study, prospective randomized placebo-controlled trials such as the Women's Health Initiative (WHI) failed to show that postmenopausal estrogen therapy in women who had undergone hysterectomy prevented death or myocardial infarction (RR = 0.95, CI = 0.79-1.16). However, subgroup analyses suggested that younger women may benefit (age 50-59, RR = 0.63, 0.36-1.08) as compared to older women (age 60-69, RR = 0.94; age 70-79, RR = 1.11). Thus, Manson and colleagues initiated an ancillary sub-study of WHI where CT coronary calcium scores were done in 1064 available women in the 50-59 years group after a mean of 7.4 years of treatment with equine estrogen (0.625 mg/day) or placebo. The CT scans were read at a central lab without knowledge of the women's treatment status.
Results: The mean calcium score was 83 in the estrogen group and 123 in the placebo group (p = 0.02) on an intention-to-treat analysis. After adjustment for confounders such as age and coronary risk factors, the difference was still significant (p = 0.03). When adjusted for actual treatment received, the difference was more significant (p = 0.002). The odds ratio of a calcium score > 300 in women 80% adherent to assigned treatment was 0.39 (p = 0.004). The authors concluded that in women < age 60 at initiation, estrogen therapy decreased calcified plaque burden in the coronary arteries as compared to placebo.
This is why Americans have lost faith in science — one day we say one thing, the next we say the opposite. It might be alright if these results were published in scientific journals and only after years of confirmatory studies were carefully analyzed and then explained to the public by the surgeon general. Instead, every brick in the wall is hyped by a hungry news media into a major study that panics everyone who is on the treatment in question or might be. Rarely after a few years is the whole wall looked at because this isn't often exciting news or there is no wall to see. Coffee is a good example; first it's bad then it's good and back and forth ad nauseum, so now no one pays any attention to coffee health studies. So as physicians, what do we do with these results? As it turns out, nothing.
There was never any serious attempt to start 70-year-old women on estrogens just to prevent heart disease. Estrogens were mainly used in perimenopausal women to relieve symptoms and this use was never prohibited by prior studies, we were just admonished to use the lowest doses for the shortest duration possible. Not rocket science considering the potential downsides of estrogen. Now we can prescribe for symptoms without the guilt that we are causing myocardial infarctions, and that we may be doing some good in certain women at risk for coronary heart disease. Until prospective outcome studies are done in these younger women, we still shouldn't prescribe estrogens just for cardioprotection.