Noncontraceptive estrogen use and cardiovascular disease.

To summarize, estrogens have powerful effects on certain biologic parameters, the alteration of which could influence cardiovascular disease risk. Estrogens have long been known to influence lipid and lipoprotein levels by decreasing LDL (the atherogenic lipoprotein) and by increasing HDL (the protective lipoprotein). THese lipid alterations could favorably influence the risk of cardiovascular disease. Estrogens also temporarily increase glucose intolerance and lower fasting glucose levels; although the former event could adversely affect cardiovascular disease risk, the clinical significance of increased glucose intolerance with low fasting levels has not been determined. There is no consistent evidence that menopausal estrogens adversely affect coagulation or blood pressure levels, although both of these parameters could be affected in selected individuals. Overall, the estrogenic effects on lipid/lipoprotein levels appear to be the most consistent and the most powerful; given this assumption, estrogens should protect against cardiovascular disease. There is another interpretation of the biologic effect of estrogens on cardiovascular risk. It is possible that estrogens may increase the risk of a thromboembolic event due to an adverse influence on coagulation parameters and, at the same time, decrease the risk of an atherogenic event (via favorably altered lipid/lipoprotein levels). This proposed dual action of estrogens may explain the apparently conflicting results of increased risks of thromboembolism and decreased risks of atherosclerosis or myocardial infarction in men treated with high doses of estrogen (36, 196, 197). In women, there is some suggestion that (low-dose) postmenopausal estrogens may increase the risk of thromboembolism (79, 204), although the majority of studies report no such increase. The difference in risk of thromboembolism between men and women using estrogens may be due to several factors. First, the dose (potency) of the estrogen used by men is usually higher than that used by postmenopausal women, and the risk of estrogen-induced thrombus formation may be dose-dependent. Second, men tend to have more atherosclerotic lesions than women and thus would have more substrate available for thrombus formation. (This hypothesis is supported by the observation that the increased risk of thromboembolism was evident in men using estrogens for the secondary prevention of cardiovascular disease.) Indirect evidence supporting the hypothesis that endogenous estrogen levels are protective against cardiovascular disease is most consistent for women.(ABSTRACT TRUNCATED AT 400 WORDS)