Effects of Transdermal Testosterone on Lipids and Vascular Reactivity in Older Men With Low Bioavailable Testosterone Levels

BACKGROUND: Sex hormones are known to affect cholesterol levels and vascular tone in women. The effects of testosterone on cholesterol and vascular tone in men are less well understood. Low testosterone levels have been associated with higher cholesterol levels in epidemiologic studies, but testosterone replacement has resulted in variable changes in cholesterol levels. Similarly, clinical studies suggest that testosterone may be vasodilatory, but few studies have directly evaluated the effects of testosterone on vascular tone. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 4.44 nmol/l (lower limit for adult normal range) were randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo patches for 1 year. Twenty-three men (34%) withdrew from the study; 44 men completed the trial. RESULTS: While total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels did not significantly change during the year of therapy, high-density lipoprotein (HDL) levels (p =.004) and, specifically, HDL(2) subfraction (p =.02) decreased in men receiving testosterone supplementation. Vascular tone was measured by brachial artery reactivity in 36 men. Endothelium-dependent brachial artery reactivity did not change from baseline measurements in men receiving transdermal testosterone (0.3 +/- 6.7% to 1.6 +/- 4.6%; p =.58) or in the placebo group (3.2 +/- 5.5% to 0.7 +/- 5.5%; p =.23). CONCLUSIONS: Transdermal testosterone decreased HDL(2) cholesterol but did not affect vascular reactivity in men older than 65 years selected for low testosterone levels. No study to date has addressed the direct relationship between testosterone replacement and cardiovascular events.