PHYSIOLOGICAL LEVELS OF ESTRADIOL STIMULATE PLASMA HIGH-DENSITY LIPOPROTEIN(2) CHOLESTEROL LEVELS IN NORMAL MEN

Premenopausal women have a lower risk of coronary artery disease than men or postmenopausal women; estrogens are thought to contribute to th is lower risk. Administration of exogenous estrogen to postmenopausal women increases plasma high density lipoprotein (HDL) cholesterol and may reduce mortality from coronary disease in users. Although many inv estigations have examined the roles of estrogen in the regulation of l ipoproteins in women, little attention has been directed to estrogen r egulation of lipids in men. We designed a paradigm to study the role o f physiological levels of estradiol (E(2)) on plasma lipoproteins in h ealthy men. We used a GnRH antagonist, Nal-Glu, to suppress endogenous steroid hormones in healthy men. We then administered testosterone (T ) enanthate (100 mg, im, weekly) to restore T levels to the baseline r ange, and we administered an aromatase inhibitor, testolactone (Teslac ), to prevent the normal conversion of T to E(2), thereby producing a selective estrogen deficiency state in normal young men. As controls, we administered Nal-Glu and T along with placebo Teslac to a separate group of men; a third group of men received all placebo medications. W e found that in men who received Nal-Glu plus T plus Teslac, E(2) leve ls were profoundly suppressed during treatment, whereas T levels remai ned in the baseline range. Plasma HDL cholesterol, particularly, the H DL(2) fraction, decreased significantly in response to the low serum E (2) level. Plasma apoprotein-AI levels also decreased significantly. P lasma LDL and triglyceride levels did not change. All hormone and lipo protein parameters returned to baseline within 4 weeks after treatment ended. In men who received Nal-Glu plus T, plasma HDL and apoprotein- AI decreased, but these decreases did not achieve statistical signific ance. Only a small decrease in HDL(2) cholesterol was seen in these me n. There were no hormonal or lipid changes in the placebo group. We co nclude that in men, physiological levels of E(2) are important in main taining plasma levels of HDL cholesterol, especially the HDL(2) fracti on. These observations suggest that estrogen, in the amount normally p roduced in men, may offer some degree of protection against cardiovasc ular disease in males, as they do in women.