DOCTOR'S VIEW ARCHIVE

Medical Author Revision: Dennis Lee, M.D.
Medical Editor: Carolyn Janet Crandall, MD, MS, FACP

After menopause, the production of estrogen by the ovaries gradually diminishes over several years. Along with this reduction, there is an increase in LDL ("bad" cholesterol) and a small decrease in HDL ("good" cholesterol). These changes in lipid levels are believed to be one of the reasons for the increased risks of developing coronary heart disease (CHD) after menopause. Women who have had their ovaries surgically removed (oophorectomy) or experience an early menopause also have an accelerated risk of CHD.

Since treatment with estrogen hormone results in higher HDL and lower LDL cholesterol levels, doctors thought for many years that estrogen would protect women against CHD (as well as protect against dementia and stroke). Many studies have found that postmenopausal women who take estrogen have lower CHD rates than women who do not. Unfortunately, many of these studies were observational (studies in which women are followed over time but decide on their own whether or not they wish to take estrogen). Observational studies have serious shortcomings because they are subject to selection bias. For example, women who choose to take estrogen hormones may be healthier and have a lower risk of heart attacks than those who do not. In other words, something else in the daily habits of women who take estrogen (such as exercise or a healthier diet) may make them less likely to develop heart attacks. Therefore, only a randomized, double-blind, placebo-controlled trial (a study in which women agree to be assigned to estrogen or a placebo or sugar pill at random but are not told which pills they took until the end of the study) can establish whether hormone therapy after menopause can prevent CHD.

HERS (Heart and Estrogen/Progestin Replacement Study) trial results

The Heart and Estrogen/Progestin Replacement Study (HERS) was a controlled trial of the effect of the daily use of estrogens plus medroxyprogesterone (progestin) on the rate of heart attacks in postmenopausal women who already had CHD. The HERS trial did not find a reduction in heart attacks in women who took hormone therapy. This lack of benefit in preventing heart attacks occurred despite an 11% lower LDL and a 10% higher HDL cholesterol level in the women treated with hormones. The study also found that more women in the hormone-treated group experienced blood clots in the veins and gallbladder disease than women in the placebo-treated group. (Blood clots in the veins are dangerous because these clots can travel to the lungs and cause pulmonary embolism, a condition with chest pain, shortness of breath, and even shock and death.) However, the increase in gallbladder disease and blood clots among healthy users of estrogen who do not have heart disease is very small.

Based on the results of this study, researchers concluded that estrogen is not effective in preventing coronary artery disease (CAD) and heart attacks in postmenopausal women who already have CAD. It should be noted, however, that the results of the HERS trial only apply to women who have known CAD prior to starting hormone therapy and not to women without known CAD.

WHI (Women's Health Initiative) trial results

The Women's Health Initiative (WHI) was the first controlled trial designed to determine the long-term benefits and risks of treatment with estrogens plus medroxyprogesterone (progestin) in healthy menopausal women (women without CAD). The results were reported in a series of articles in 2002, 2003, and 2004. The estrogen + progestin portion of the WHI study had to be stopped earlier than planned (after just 5.2 years) because the increase in coronary heart disease, stroke, and pulmonary embolism among women who used estrogen + progesterone outweighed the benefits of reduced bone fractures and colon cancer. The estrogen-alone portion of the WHI was stopped because women who took estrogen alone had no reduction in heart attack risk, yet there was a significant increase in stroke risk.

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