Abstract
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/m2 , 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 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.
Original language | English |
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Journal | Andrology |
Volume | 12 |
Issue number | 1 |
Pages (from-to) | 115-122 |
ISSN | 2047-2919 |
DOIs | |
Publication status | Published - Jan 2024 |
Keywords
- aging
- hypogonadism
- testosterone
- whole-body oxidative stress
- Body Composition
- Double-Blind Method
- Oxidative Stress
- Humans
- Male
- Insulin
- Testosterone/therapeutic use
- Aging
- 8-Hydroxy-2'-Deoxyguanosine