Association between chronic inflammation status and serum testosterone and free testosterone in adult males

Chronic inflammation may contribute to biochemical hypogonadism, but evidence regarding composite inflammatory indicators is limited. This study examined the associations of the systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) with serum testosterone and free testosterone (FT) in adult males.

Data were obtained from NHANES 2011-2016 and 2021-2023, including 7,576 men for serum testosterone and 3,590 for FT. Multivariable regression, smoothing curves, threshold effect, and age-stratified analyses were conducted.

Higher SIRI and AISI were significantly associated with lower serum testosterone and FT levels (P < 0.0001). Testosterone levels were lowest in the highest quartiles of SIRI and AISI. Nonlinear inverse associations with serum testosterone were observed for both indices, and AISI also showed a nonlinear association with FT, while SIRI showed a linear inverse association. A positive association with biochemical hypogonadism was observed only when defined by serum testosterone. The inverse associations were consistent across all ages for serum testosterone but were evident for FT only in men aged 20-39 and ≥60 years.

SIRI and AISI are independently associated with lower serum testosterone in men, while associations with FT appear age-dependent.