Endocrine Abstracts

Background: High oxidative stress is associated with increased morbidity. The effect of testosterone treatment (TT) on oxidative stress in ageing men with reduced bioavailable testosterone is undetermined.

Aim: To determine the effect of TT compared to placebo on oxidative stress biomarkers.

Methods: Double-blinded, placebo-controlled study in 38 men, aged 60–78 years, with bioavailable testosterone <7.3 nmol/l and waist circumference ≥ 94 cm, randomized to six-month testosterone gel therapy (n=20) or placebo (n=18). Whole body oxidative stress was assessed at baseline and after 6 months therapy by measuring 24-h urine oxidized derivatives of nucleic acids: 8-oxoguanosine (8-oxoGuo) and 8-oxo-2’-deoxyguanosine (8-oxodG) by ultra-performance liquid chromatography tandem mass-spectrometry. Fat and lean mass were measured by whole body dual x-ray absorptiometry. Changes between TT and placebo groups were compared using Mann-Whitney test. Δ-values for clinical and biochemical markers were calculated as 6 months minus pretreatment level. Bivariate associations of Δ-values of clinical and biochemical data were investigated by Spearman’s Rho correlational analyses. Linear regression analysis was used to adjust for changes in body composition. P-value of < 0.05 was considered significant.

Results: At baseline, median (interquartile range) age was 67 (64-72) years, BMI 29.8 (26.6-33.3 kg/m2, total testosterone 12.6 (8.9-16.1) and bio-available testosterone 4.7 (3.7-5.9) nmol/l. Levels of 8-oxodG/24h decreased during TT compared to placebo (P=0.038). Δ8-oxoGuo/24h was inversely associated with Δ-total testosterone (ρ=-0.35, P=0.04) and Δ-bio-available testosterone (ρ=-0.37, P=0.03). Δ-8-oxoGuo/24h and Δ-8-oxodG/24h were associated with Δ-fat mass (ρ=0.47, P=0.006 and ρ=0.40, P=0.02, respectively). Δ-8-oxodG/24h was inversely associated with Δ-lean mass (ρ=-0.38, P=0.03). In linear regression analyses. The inverse association between Δ-oxidative stress biomarkers and Δ-total testosterone remained significant after adjustment for Δ-fat mass and Δ-lean mass.

Conclusion: Oxidative stress biomarkers decreased during six-month TT compared to placebo in ageing men.