Associations of Obesity, Inflammatory Indicators, and Serum Testosterone in Adult Males: A Cross-Sectional Study Based on NHANES 2011–2016 and 2021–2023

Obesity significantly contributes to declining serum testosterone levels in men, with chronic inflammation being a crucial potential mechanism; Clinical research evidence directly supporting this pathway remains limited. We investigated how obesity relates to serum testosterone in males, with particular attention to the intermediary role of chronic inflammation. Our study included adult males aged ≥20 years from the National Health and Nutrition Examination Surveys (NHANES) conducted from 2011 to 2016 and from 2021 to 2023. Obesity status was assessed with body mass index (BMI), body roundness index (BRI), and waist circumference (WC). Chronic inflammatory status was assessed with an aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Multivariable regression assessed associations between obesity metrics and testosterone. The indirect influence of inflammatory indicators was assessed through mediation analysis. Subgroup analyses were performed by weight status. The study comprised 7,418 participants. Multivariable linear regression revealed that obesity (BMI, WC, BRI) was negatively associated with male serum testosterone. Generalized additive models indicated a nonlinear relationship, showing a clear inverse association. Chronic inflammatory status (SII, SIRI, and AISI) mediated the association between obesity and male serum testosterone. In subgroup analyses, the association was consistent with overall findings, but the mediating effect of chronic inflammatory status was statistically significant only in the group with obesity (BRI ≥4.5, WC ≥102 cm, and BMI ≥30 kg/m 2 ). Obesity was inversely associated with serum testosterone in adult males. Chronic inflammatory status may partly explain this association, particularly among individuals with obesity.