Association between systemic immune inflammation index and serum testosterone and free testosterone in middle‐aged and elderly men

Abstract Background Chronic inflammation is a pervasive feature of aging and may be associated with testosterone in middle‐aged and older men. Systemic immune‐inflammation index (SII) is a novel inflammatory biomarker. We aimed to assess the association between SII and serum testosterone and free testosterone (FT) in middle‐aged and older men. Methods Our study included males ≥ 40 years old in the 2011–2016 and 2021–2023 National Health and Nutrition Examination Survey. Multivariable regression analysis was used to explore the associations between SII and serum testosterone and FT in middle‐aged and older men. Subgroup analysis was performed according to age. Results About 5354 participants were included, of which 2450 contained FT data. Multivariable linear regression found that SII exhibited an inverse association with serum testosterone (β −0.05, 95% CI −0.07 to −0.03, P < 0.001) and FT (β −0.03, 95% CI −0.05 to −0.01, P = 0.032) in middle‐aged and elderly men. After SII was grouped as quartiles, serum testosterone was significantly lower in SII quartile 4 than in SII quartile 1 (β −0.05, 95% CI −0.08 to −0.02, P < 0.001). However, FT was not significantly lower in SII quartile 4 than in SII quartile 1 (β −0.03, 95% CI −0.07 to 0.01, P = 0.135). In subgroup analysis, the serum testosterone results were consistent with the overall results. However, only in the ≥60 years group, SII exhibited an inverse association with FT (β −0.06, 95% CI −0.1 to −0.02, P = 0.002) and was significantly lower in SII quartile 4 than in SII quartile 1 (β −0.06, 95% CI −0.12 to −0.01, P = 0.049). Conclusions Our study revealed an inverse association between SII and serum testosterone and FT in middle‐aged and elderly men, particularly among men ≥ 60 years.