The indication for
testosterone therapy in aging 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 aging men with low normal bioavailable
testosterone levels using a predefined cutoff level for bioavailable
testosterone. A randomized, double-blinded, placebo-controlled study of
testosterone treatment (gel) was done on 38 men, aged 60-78 years, with bioavailable
testosterone <7.3 nmol/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 (TFM) were measured by dual x-ray absorptiometry, and serum total
testosterone was measured by tandem mass spectrometry. Bioavailable
testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b = 1.9 kg, p = 0.003) increased while
HDL-cholesterol (b = -0.12 mmol/l, p = 0.043) and TFM decreased (b = -1.2 kg, p = 0.038) in the
testosterone group compared to placebo. Basal
lipid oxidation (b = 5.65 mg/min/m(2), p = 0.045) increased and basal
glucose oxidation (b = -9.71 mg/min/m(2), p = 0.046) decreased in response to
testosterone therapy even when corrected for changes in LBM. No significant changes in
insulin-stimulated Rd was observed (b = -0.01mg/min/m(2), p = 0.92).
Testosterone therapy increased muscle mass and
lipid oxidation in aging men with low normal bioavailable
testosterone levels; however, our data did not support an effect of
testosterone on whole-body
insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.