Endocrine Abstracts

Background: The indication for testosterone therapy in ageing hypogonadal men without hypothalamic, pituitary or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition and lipids in ageing men with relative hypogonadism using a predefined cut-off level for bioavailable testosterone.

Methods: A randomized, double-blinded, placebo-controlled study of testosterone treatment (gel) on 38 men, aged 60–78 years, with bioavailable testosterone <7.3 mmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass were measured by DXA, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention.

Results: Lean body mass (b=1.9 kg, P=0.003) increased while HDL-cholesterol (b=−0.12 mmol/l, P=0.043) and total fat mass (TFM) decreased (b=−1.2 kg, P=0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b=5.65 mg/min per m², P=0.045) increased and basal glucose oxidation (b=−9.71 mg/min per m², P=0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No change in insulin-stimulated Rd was observed (b=−0.01 mg/min per m², P=0.92).

Conclusion: Testosterone therapy increased muscle mass and lipid oxidation in the absence of an effect on insulin-stimulated glucose uptake. These data suggest the existence of opposite-directed effects of testosterone on factors related to insulin sensitivity in ageing men with relative hypogonadism.