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Sex steroid concentrations linked with lean mass changes in men
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Higher serum concentrations of testosterone, dihydrotestosterone and estradiol were all linked to greater increases in lean mass and decreases in fat mass among healthy men who were medically castrated. However, study data showed no effect on serum glucose, insulin or adipokines.
“Untreated hypogonadism adversely impacts body composition, bone mass and sexual function in men and has been associated with an increased risk of diabetes, cardiovascular disease and even early mortality,” Arthi Thirumalai, MD, acting assistant professor of medicine at the University of Washington, Seattle, and colleagues wrote. “Recent findings have shown dose-dependent changes produced by exogenous [testosterone] on body composition and threshold sex steroid concentrations below which tissue-specific symptoms of hypogonadism might develop. However, whether these effects are direct or indirect, and whether they depend upon the dose of exogenous [testosterone] given or the concentrations of its downstream metabolites, dihydrotestosterone and/or estradiol achieved, has not been explored.”
The researchers randomly assigned 48 men to acyline injections every 2 weeks plus daily transdermal testosterone gel (1.25 g, 2.5 g, 5 g, 10 g or 15 g) or double placebo for 12 weeks. Men ranged in age from 22 to 25 years and had normal serum total testosterone concentrations, and acyline was used to render them medically castrated. Thirumalai and colleagues measured serum testosterone, dihydrotestosterone and estradiol at baseline and every 2 weeks; body composition at baseline and week 12; and fasting serum adiponectin, leptin, glucose and insulin concentrations at baseline and week 10.
Treatment significantly affected lean mass (P = .01), the researchers reported, but not fat mass (P = .14). Patients assigned to the 15-g testosterone group experienced increases in lean mass compared with all lower-dose groups except the 10-g group. Overall, Thirumalai and colleagues reported a direct correlation between lean mass and serum testosterone, while fat mass was inversely correlated with testosterone, estradiol and dihydrotestosterone concentrations. The researchers reported no changes in serum levels of glucose, insulin or adipokines. The patients’ body weight was stable throughout the study.
“Our findings support a concentration-dependent relationship between serum sex steroid and body composition changes in men,” the researchers wrote. “Ultimately this line of investigation has the potential to better define optimal [testosterone replacement therapy] regimens on an individual basis and thereby enable delivery of a therapy that confers the desired androgenic effects while minimizing cardiometabolic risk.” – by Andy Polhamus
Disclosure: Transdermal testosterone gel and placebo gel were both provided by Besins Healthcare as an investigator-initiated grant. The researchers report no relevant financial disclosures.
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