Context: In obese men with lowered testosterone levels, testosterone treatment augments the diet-associated loss of body fat.
Objective:We hypothesized that testosterone treatment modulates the circulating concentrations of hormonal mediators of fat mass and energy homeostasis in obese men subjected to a rigorous weight loss program.
Design: Pre-specified secondary analysis of a randomized double-blind, placebo-controlled trial.
Setting: Tertiary referral centre.
Participants: Obese men (body mass index >30kg/m2) with a repeated total testosterone level <12nmol/L.
Intervention: One hundred participants aged 53 years (IQR 47-60) 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 (n= 49, cases) or matching placebo (n= 51, controls). Eighty-two men completed the study.
Main outcome measures:Between-group differences during follow-up in leptin, adiponectin, ghrelin, glucagon-like peptide-1, gastric inhibitory polypeptide, peptide YY, pancreatic polypeptide, and amylin.
Results: At study end, compared to controls, cases had greater reductions in leptin (MAD -3.6ng/ml[-5.3,-1.9], p<0.001). The change in leptin levels between testosterone and placebo treated men was dependent on baseline fat mass, as the between-group difference progressively increased with increasing fat mass (MAD -0.26ng/ml [-0.31,-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 leads to reductions in leptin over and above those achieved by diet-associated weight loss. Testosterone treatment may reduce leptin resistance in obese men.