Effects of varying doses of testosterone on atherogenic markers in healthy younger and older men.

Whether exogenous testosterone is proatherogenic remains controversial. We assessed the effects of graded doses of testosterone on serum markers of oxidative stress, chemotaxis, adhesion, and inflammation in healthy younger and older men. In a double-blind, randomized trial, 121 eugonadal men (n = 61, 18-35 years of age and n = 60, 60-75 years of age) were randomized to one of five groups to receive weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk, respectively, along with a long-acting gonadotropin-releasing hormone (GnRH) agonist. Energy and protein intakes were standardized and no resistance training was allowed. We measured plasma levels of the atherogenic biomarkers monocyte chemotactic protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1), 8-isoprostane-PGF(2α) (8-iso-PGF(2α)), and high-sensitivity C-reactive protein (hs-CRP) before and after the intervention. Administration of increasing doses of testosterone led to reduction in total 8-iso-PGF(2α) in the younger (p-trend(Younger) = 0.01), but not older (p-trend(Older) = 0.79) men. No significant linear associations were observed between testosterone dose and MCP-1, sICAM-1, or hs-CRP (all p-trend >0.20). In apparently healthy men, over a wide dose range, testosterone did not adversely affect atherogenic biomarkers. Long-term studies with larger sample sizes are warranted to determine whether testosterone supplementation affects atherosclerosis progression and cardiovascular risk.