Physiologic Testosterone Levels in Normal Men Suppress High-Density Lipoprotein Cholesterol Levels

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Abstract
▪ Objective: To investigate the role of physiologic levels of testosterone in the control of lipoproteins in healthy men. ▪ Design: A double-blind, randomized study. ▪ Setting: A university community. ▪ Participants: Fifteen healthy men, ages 20 to 36 years. ▪ Intervention: We induced acute, reversible hypogonadism in five normal men by administering daily subcutaneous injections of the gonadotropin-releasing-hormone (GnRH) antagonist, Nal-Glu, for 6 weeks. Another group of five normal men received Nal-Glu plus weekly injections of testosterone enanthate, 100 mg/wk, thereby maintaining normal serum testosterone levels. Five additional men received placebo injections. ▪ Measurements: Plasma lipids, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, apoprotein A1, and serum levels of gonadotropins, estradiol, and testosterone were measured before, during, and after treatment. ▪ Results: At the end of the treatment period, HDL cholesterol levels in men receiving Nal-Glu increased by 26% (95% Cl, 18% to 34%; P < 0.05). Levels of HDL2, HDL3, and apoprotein A1 increased by 63% (Cl, 16% to 110%), 17% (Cl, 3% to 31%), and 17% (Cl, 5% to 29%), respectively (P < 0.05 for each parameter). Total cholesterol increased by 12% (Cl, 2% to 22%). Low-density lipoprotein (LDL) cholesterol and triglyceride concentrations did not change. No statistically significant changes occurred in any lipid measurement in men receiving Nal-Glu plus androgen replacement or placebo (P > 0.05). ▪ Conclusions: Experimental hypogonadism induced by administration of a GnRH antagonist results in a statistically significant increase in HDL cholesterol, including HDL2 and HDL3. These effects are most likely due to decreased androgen levels because they are reversed by administration of antagonist together with testosterone. Our results imply that androgen levels in the normal adult male range have a suppressive effect on HDL cholesterol concentration and may contribute to the increased risk for coronary artery disease in men.