Dorte Glintborg

Background Testosterone 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. Objectives To 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 methods This 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 ∆‐values (24–0 weeks). Results Baseline 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) n m to 15.0 (12.2; 18.8) n m ( 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 Δ‐lean body mass ( ρ = –0.38, p = 0.03), which remained significant after adjusting for Δ‐total testosterone. 8‐Oxo‐2′‐deoxyguanosine in 24‐h urine samples was unchanged ( p = 0.06) during testosterone replacement therapy and Δ‐8‐oxo‐2′‐deoxyguanosine in 24‐h urine samples was associated with Δ‐whole‐body fat (kg) ( ρ = 0.47, p < 0.01). Δ‐Values of oxidative stress biomarkers were not associated with Δ‐fasting insulin or Δ‐homeostatic model assessment of insulin resistance. Discussion Oxidative stress decreased during testosterone replacement therapy compared to placebo, which could be mediated by changed body composition. Conclusion Whole‐body oxidative stress decreased during 24 weeks of testosterone replacement therapy in aging men.