Focus on cardiovascular health: hormone replacement therapy, estrogen replacement therapy, and selective estrogen receptor modulators.

Walsh • Focus on cardiovascular health C disease is the leading cause of death in the United States today. Fully 52% of women will die of cardiovascular disease, far exceeding the percentage who will die of all cancers combined, and far in excess of the 4% who will die of breast cancer.1 It has been known since the initial findings of the Framingham Study, however, that women have a 20-year advantage over men in the occurrence of their first coronary event.2 The causes underlying this observed delay in women are not known. Hormonal differences are an obvious starting point, and menopause—the loss of estrogen—provides a potential mechanism for explaining the two-decade delay. This theory, the estrogen hypothesis, holds that estrogen conveys a protective effect against the development of cardiovascular disease, which is then lost on menopause. A number of studies have examined the biological plausibility of this hypothesis using surrogate cardiovascular end points. In one study of healthy postmenopausal women, two doses of conjugated equine estrogens (0.625 mg/d and 1.25 mg/d) were compared with placebo in their effect on various laboratory values. Estrogen was associated with reductions in low-density lipoprotein cholesterol (LDL-C) levels, and increases in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels (Figure).3 Reductions in LDL-C and increases in HDL-C should be beneficial, although increases in triglyceride concentrations could be harmful. Similar studies have found other potential benefits of estrogen therapy in surrogate markers of cardiovascular disease. These studies provided some plausibility to the estrogen hypothesis. Data from observational studies of hormone use also suggested a protective effect against cardiovascular disease. Analysis of relative risks from a number of studies indicate a lower incidence of heart disease in women receiving hormone therapy, with few exceptions. Again, it is important to be cognizant of the various biases inherent in such studies and the limited conclusions that can be drawn from them.