Testosterone Deficiency, Long-Term Testosterone Therapy, and Inflammation.

Objectives: We aimed to evaluate the association of testosterone deficiency with inflammation and how long-term testosterone therapy affects inflammation biomarkers over time.

Methods: We conducted a 2-component study. First, we conducted a cross-sectional study using the recently released 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to examine the association between testosterone deficiency and inflammation biomarkers including high sensitivity C-reactive protein (hsCRP), liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the US general population. Then we conducted a longitudinal study to investigate the longitudinal effect of testosterone therapy on inflammation biomarkers and the risk of cardiovascular events, using data from 776 hypogonadal men based on a registry study in Germany with up to 11 years' follow-up.

Results: The adjusted odds ratios (ORs) describing the associations between testosterone deficiency and hsCRP ≥ 3mg/L, ALT > 40U/L, and AST > 40U/L were 1.81 (P-value < 0.001), 1.46 (P-value = 0.009), and 0.99 (P-value = 0.971), respectively. In the control group, CRP, ALT, and AST levels increased by 0.003 (95%CI: -0.001, 0.007) mg/L, 0.157 U/L (95%CI: 0.145, 0.170), and 0.147 (95%CI: 0.136, 0.159) U/L per month, while in the treatment group, CRP, ALT, and AST levels decreased by 0.05 (95%CI: -0.055, -0.046) mg/L, 0.142 U/L (95%CI: -0.154, -0.130), and 0.148 (95%CI: -0.158, -0.137) U/L per month.

Conclusion: Testosterone deficiency was associated with an increased level of inflammation; long-term testosterone therapy alleviated inflammation among hypogonadal men, which may contribute to the reduced cardiovascular risk. Future large trials are warranted to confirm our observational study findings.