Effect of Testosterone Treatment on Adipokines and Gut Hormones in Obese Men on a Hypocaloric Diet

CONTEXT: In obese men with lowered testosterone levels, testosterone treatment augments diet-associated loss of body fat. OBJECTIVE: We hypothesized that testosterone treatment modulates circulating concentrations of hormonal mediators of fat mass and energy homeostasis in obese men undergoing a weight loss program. DESIGN: Prespecified secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Tertiary referral center. PARTICIPANTS: Obese men (body mass index ≥30 kg/m(2)) with a repeated total testosterone level ≤12 nmol/L. INTERVENTION: One hundred participants mean age 53 years (interquartile range 47 to 60 years) receiving 10 weeks of a very low–energy diet followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (cases, n = 49) or matching placebo (controls, n = 51). Eighty-two men completed the study. MAIN OUTCOMES: Between-group differences in leptin, adiponectin, ghrelin, glucagon like peptide-1, gastric inhibitory polypeptide, peptide YY, pancreatic polypeptide, and amylin levels. RESULTS: At study end, compared with controls, cases had greater reductions in leptin [mean adjusted difference (MAD), −3.6 ng/mL (95% CI, −5.3 to −1.9); P < 0.001]. The change in leptin levels between cases and controls was dependent on baseline fat mass, as the between-group difference progressively increased with increasing fat mass [MAD, −0.26 ng/mL (95% CI, −0.31 to −0.26); P = 0.001 per 1 kg of baseline fat mass]. Weight loss–associated changes in other hormones persisted during the weight maintenance phase but were not modified by testosterone treatment. CONCLUSIONS: Testosterone treatment led to reductions in leptin beyond those achieved by diet-associated weight loss. Testosterone treatment may reduce leptin resistance in obese men.