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/m2) 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.