Abstract
Background and objectives: Although data suggest a bidirectional relationship between serum testosterone and inflammation, studies on treatment with exogenous testosterone report inconsistent effects on markers of inflammation. We performed a systematic review and meta-analysis to synthesize evidence on how testosterone therapy affects circulating inflammatory biomarkers in adult males.
Materials and methods: PubMed (MEDLINE), Scopus, Embase, and Web of Science were searched from inception to May 2024 for trials in which testosterone was administered for any indication and inflammatory cytokine concentrations were measured. Methodological quality was assessed with the modified Joanna Briggs Institute critical appraisal checklist.
Results: From 6,502 records, 17 studies (n = 1,765) met inclusion criteria; 955 participants received testosterone therapy and 871 served as controls. Testosterone had no significant effect on IL-6 (SMD = –0.04, 95% CI = [–0.09, 0.16]; p = 0.56), TNF-α (SMD = –0.17, 95% CI = [–0.47, 0.14]; p = 0.29), hs-CRP (SMD = –0.19, 95% CI = [–0.41, 0.04]; p = 0.10) or adiponectin (SMD = –0.07, 95% CI = [–0.70, 0.56]; p = 0.82). It produced a marked reduction in IL-1β (SMD = –0.66, 95% CI = [–1.01, –0.32]; p < 0.0001). Leptin fell significantly (SMD = –0.87, 95% CI = [–1.36, –0.38]; p = 0.0005), all studies consistently reporting decrement. Two trials also reported an increase in IL-10 relative to placebo.
Conclusions: Testosterone therapy exerts selective anti-inflammatory effects, particularly lowering IL-1β and leptin, while leaving several other cytokines unchanged. These findings highlight the complex, context-dependent nature of testosterone’s immunomodulatory actions and support further mechanistic research.