Hormone replacement therapy and coronary heart disease

As I’ve written in a previous post, the Women’s Health Initiative (WHI) examined the risks of heart disease, breast cancer, and osteoporosis in post-menopausal women. One aspect of the WHI was randomized trials investigated the effects of hormone therapy (either estrogen alone or estrogen plus progestin) on the health of post-menopausal women. The study was shut down early due to a high number of adverse effects. From the data that was collected while the study was ongoing came the somewhat surprising result that women receiving the hormone therapy were not at any reduced risk for non-fatal myocardial infarction (heart attacks) or coronary artery disease. This was surprising because it had long been thought that estrogen supplied some sort of cardioprotective function (this was the explanation for why pre-menopausal women have lower risk of heart attacks than men of similar age). Follow-up analyses after the WHI trial ended showed that the effect of estrogen on the heart seemed to be time dependent – the earlier the estrogen was administered, the more cardioprotective the result. In women aged 50-59, there was a fairly notable beneficial effect of hormone therapy. In older women, there was either no benefit, or, in the 70-79 cohort, perhaps some detriment to the hormone therapy.

A recent study in the New England Journal of Medicine looked at atherosclerotic calcification of women in the 50-59 year-old cohort using computed tomography, comparing women who had received hormones and those that hadn’t. The women studied had been part of the initial WHI study (estrogen only trial - so all the women lacked a uterus). Technicians at a central lab scored all the scans for calcification. In the end, women that had received estrogen during the WHI trial had less calcification than women that received a placebo.

The authors conclude:

The new findings from WHI-CACS [CACS = Coronary Artery Calcium Study; the name of the follow-up analysis] indicate that estrogen therapy initiated in women at 50 to 59 years of age is related to a reduced plaque burden in the coronary arteries and a reduced prevalence of subclinical coronary artery disease, providing support for the hypothesis that estrogen therapy may have cardioprotective effects in younger women.

The authors also provide a potential explanation for why estrogen might be cardioprotective in recently post-menopausal women (50-59 years old), but have negative effects on older women (70-79):

It is possible that estrogen could reduce coronary-artery calcium scores but still increase the risk of clinical CHD [coronary heart disease] events, owing to adverse effects on thrombosis and plaque rupture, which are more likely in older women with advanced stages of atherosclerosis. Such a duality of effects would not necessarily apply to younger women with lower burdens of atherosclerosis.

But nobody should get carried away with hormone replacement therapy; it still has significant risks. Any decision to initiate hormone therapy is still a balanace between those risks and the benefits:

In the meantime, hormone therapy should not be initiated (or continued) for the express purpose of preventing cardiovascular disease in either younger or older postmenopausal women. The current recommendations from many organizations that hormone therapy be limited to the treatment of moderate-to-severe menopausal symptoms, with the lowest effective dose used for the shortest duration necessary, remain appropriate.

References:

1. Manson, J.E. et al. (2007). "Estrogen Therapy and Coronary Artery Calcification." New England Journal of Medicine 365: 2591-25602. (Available for free after 6 months)

2. WHI steering committee (2004). "Effects of Conjugated Equine Estrogen in Post-menopausal Women with Hysterectomy." Journal of the American Medical Association 291(14): 1701-1712. (Free with registration)