The effects of estradiol on blood lipids and lipoproteins in postmenopausal women

Endogenous sex steroids seem to exert a major influence on plasma lipoprotein levels. During menopause, endogenous estradiol (E2) levels decrease, and the low-density lipoprotein cholesterol concentration, which gradually increases with age, rises more rapidly, with mean plasma levels exceeding those of age-matched men. It is surprising that the reduction of endogenous E2 does not appear to influence high-density lipoprotein cholesterol levels. Women who experience early menopause have a higher incidence of coronary heart disease than do premenopausal women of similar age; however, this risk is decreased in women treated with oral estrogens. Oral administration of E2 increases plasma concentrations of estrone, E2, and high-density lipoprotein cholesterol, and decreases plasma concentrations of total and low-density lipoprotein cholesterol. This effect seems to be dose-dependent. Increased high-density lipoprotein (HDL) cholesterol concentration depends primarily on an HDL2 subfraction increase. It is interesting to speculate that the effects of oral estrogen replacement on plasma lipoproteins might be important in reducing coronary heart disease risk. Sequential addition of progestogens attenuates the effects of estrogen on plasma lipids and lipoproteins to some degree. However, the type and dose of the progestogen are important. Most progestogens derived from 19-nortestosterone, for example, reduce high-density lipoprotein cholesterol and, in higher doses, increase low-density lipoprotein cholesterol levels. In contrast, progestogens derived from 17-hydroxyprogesterone exert only minor effects on plasma lipoproteins. As with oral contraceptives, the net effect of estrogen-progestogen replacement therapy on plasma lipoproteins depends on the dose and potency of the involved drugs.