Hormone replacement therapy and cardiovascular disease

A large amount of research continues to be conducted on the mechanisms of hormone replacement therapy (HRT) effects, and the first of the large clinical trials published its results during the past year. In addition to the well known effects on LDL-cholesterol, HDL-cholesterol, and triglycerides, recent studies confirmed that estrogen with or without a progestin lowers lipoprotein (a) concentrations in women (but not in men). In men, estrogen appears to have a similar effect on other lipids and lipoproteins and on plasminogen activator inhibitor-1 as in women. A comparison of estrogen with simvastatin indicated that simvastatin is better at lowering LDL-cholesterol while estrogen is better at raising HDL-cholesterol; when given in combination the additional effects were modest. Estrogen and simvastatin had similar beneficial effects on endothelial function. The estrogen effect on endothelial function may be blocked by medroxyprogesterone, but the data are inconsistent. These studies of intermediate outcomes were put in perspective by the results of a landmark secondary prevention trial of coronary heart disease (CHD). This randomized placebo-controlled trial (Heart and Estrogen/Progestin Replacement Study) of conjugated equine estrogens plus medroxyprogesterone failed to show the anticipated reduction in CHD, and at the same time the threefold increase in venous thromboembolism confirmed that HRT is procoagulant. Therefore, it is still not known whether HRT is a viable option for the prevention of CHD. The preliminary data on selective estrogen receptor modulators are not overly promising, but a definitive trial to test whether raloxifene will reduce CHD is ongoing.