Cj. Bagatell et al., PHYSIOLOGICAL LEVELS OF ESTRADIOL STIMULATE PLASMA HIGH-DENSITY LIPOPROTEIN(2) CHOLESTEROL LEVELS IN NORMAL MEN, The Journal of clinical endocrinology and metabolism, 78(4), 1994, pp. 855-861
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.