The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity

Abstract

Stanozolol, an oral 17α-alkylated androgen, increases hepatic triglyceride lipase activity (HTGLA) and decreases high-density lipoprotein cholesterol (HDL-C) levels, whereas intramuscular testosterone has comparatively little effect. In the present study, we tested the hypothesis that aromatization of androgen to estrogen blunts the lipid and lipase effects of exogenous testosterone. Fourteen male weightlifters received testosterone enanthate (200 mg/wk intramuscularly), the aromatase inhibitor testolactone (250 mg four times per day), or both drugs together in a randomized cross-over design. Serum testosterone level increased during all three drug treatments, whereas estradiol level increased only with testosterone alone (+47%, P < .05), demonstrating that testolactone effectively inhibited testosterone aromatization. Testosterone decreased HDL-C (−16%, P < .05), HDL 2-C (−23%, NS), and apoprotein (apo) A-I (−12%, P < .05) levels, effects that were consistently but not significantly greater with simultaneous testosterone and testolactone administration (HDL-C, −20%; HDL 2-C, −30%; apo A-I, −15%; P < .05 for all). In contrast, both testosterone regimens decreased HDL 3-C levels by 13% ( P < .05 for both). HTGLA increased 21% during testosterone treatment and 38% during combined testosterone and testolactone treatment ( P < .01 for both). Lipoprotein lipase activity (LPLA) increased only during combined testosterone and testolactone treatment (+31%, P < .01), suggesting that estrogen production may counteract the effects of testosterone on LPLA. Testolactone alone had little effect on any lipid, lipoprotein, apoprotein, or lipase concentration. We conclude that aromatization of exogenous testosterone to estradiol inhibits androgen-mediated elevations in HTGLA and reductions in HDL 2-C and apo A-I, but the effect is small and does not account for the markedly different lipid and lipase effects between oral androgens and intramuscular testosterone.