Whole-body oxidative stress reduction during testosterone therapy in aging men: A randomized placebo-controlled trial

BackgroundTestosterone replacement therapy in aging men increases lean body mass and decreases whole-body fat. The safety of testosterone replacement therapy concerning cardiovascular disease is unresolved and assessment of whole-body oxidative stress may contribute to future decision making. ObjectivesTo determine whole-body oxidative stress during testosterone replacement therapy and placebo in aging men and evaluate if a change in oxidative stress was mediated by changed body composition. Materials and methodsThis was a double-blinded, randomized, placebo-controlled study for 24 weeks in 38 men aged 60-78 years with bioavailable testosterone <7.3 nmol/L and waist circumference >= 94 cm who were randomized to testosterone replacement therapy (testosterone gel) (N = 20) or placebo (N = 18). At baseline and after 24 weeks, whole-body oxidative stress was assessed by oxidized derivatives of nucleic acids, 8-oxoguanosine and 8-oxo-2 '-deoxyguanosine in 24-h urine samples by ultra-performance liquid chromatography tandem mass spectrometry. Lean body mass and whole-body fat were measured by dual X-ray absorptiometry. Subcutaneous and visceral adipose tissue were estimated by magnetic resonance imaging. Testosterone replacement therapy versus placebo was compared by Mann-Whitney tests on increment -values (24-0 weeks). ResultsBaseline age was 67 (64-72) years (median [interquartile range]), body mass index 29.8 (26.6-33.3) kg/m(2), waist 107 (99-117) cm, and bioavailable testosterone 4.7 (3.7-5.9) nmol/L. During testosterone replacement therapy, 8-oxoguanosine in 24-h urine samples decreased from 21.6 (19.8; 27.7) nm to 15.0 (12.2; 18.8) nm (p = 0.038 vs. placebo), lean body mass increased (p < 0.01) and whole-body fat (p = 0.02) and subcutaneous adipose tissue (p < 0.01) decreased. 8-Oxoguanosine in 24-h urine samples was inversely associated with Delta-lean body mass (rho = -0.38, p = 0.03), which remained significant after adjusting for Delta-total testosterone. 8-Oxo-2 '-deoxyguanosine in 24-h urine samples was unchanged (p = 0.06) during testosterone replacement therapy and Delta-8-oxo-2 '-deoxyguanosine in 24-h urine samples was associated with Delta-whole-body fat (kg) (rho = 0.47, p < 0.01). Delta-Values of oxidative stress biomarkers were not associated with Delta-fasting insulin or Delta-homeostatic model assessment of insulin resistance. DiscussionOxidative stress decreased during testosterone replacement therapy compared to placebo, which could be mediated by changed body composition. ConclusionWhole-body oxidative stress decreased during 24 weeks of testosterone replacement therapy in aging men.