Cardioprotection by estrogens: mechanisms of action--the lipids.

Reductions of total and LDL-cholesterol and, to a lesser extent, increase in HDL are known to decrease cardiovascular disease (CVD) incidence. All oral estrogens are known to induce such changes in a dose-dependent manner at doses commonly used in ERT, somewhat more markedly for estradiol than for conjugated equine estrogens (CEE). Low-dose estriol used for urogenital discomfort is void of lipid effect. Transdermal estradiol induces similar reductions in the important LDL fraction, whereas HDL is less affected. Modified, especially oxidized, LDL is particularly atherogenic. Accumulating evidence suggests estrogen inhibits LDL oxidation in a process not counteracted by progestins. Elevated triglycerides are considered an important risk factor in women aged about 50. Oral estradiol and, especially, conjugated estrogens augment serum triglycerides, whereas estrogens with non-oral delivery systems rather reduce triglyceride concentrations. The clinical significance of pharmacologically induced changes in triglycerides remains to be clarified. Estrogen-induced changes in the serum lipid profile, however, account for no more than a third of the cardioprotective effect. Lipoprotein (a), another important indicator of CVD risk, is probably also reduced by the action of estrogens. Neither lipoprotein (a) nor oxidized LDL is measured by the routine serum lipid profile. At this time it is impossible to deduce the quantitative importance of changes in these two variables with respect to cardioprotection by estrogens.