Oxford University Press (OUP), The Journal of Clinical Endocrinology & Metabolism, 2021
Abstract Background Illicit use of anabolic androgenic steroids (AAS) is frequently observed in men and is associated with subsequent testosterone deficiency although the long-term effect on gonadal function is still unclear. Serum insulin-like factor 3 (INSL3) has been suggested to be a superior biomarker of Leydig cell secretory capacity compared to testosterone. The objective of this study was to investigate serum INSL3 concentrations in AAS users. Methods This community-based cross-sectional study included men aged 18 – 50 years, involved in recreational strength training and allocated to one of three groups: never-AAS users as controls (n=44), current (n=46) or former AAS users (n=42) with an average duration since AAS cessation of 32 (23;45) months. Results Serum INSL3 was lower in current AAS users and former AAS users than in controls, median (IQR), 0.04 (ND – 0.07) and 0.39 (0.24 – 0.62) versus 0.59 (0.45 – 0.72) µg/L, P<0.001. Former AAS users exhibited lower serum INSL3 levels than controls in a multivariate linear regression even after adjusting for serum total testosterone and other relevant confounders, (B) (95%CI), -0.16 (-0.29;-0.04) µg/L, P=0.011. INSL3 and total testosterone were not associated in the model, P=0.821. Longer accumulated AAS duration (log2) was associated with lower serum INSL3 in former AAS users, (B) (95%CI), -0.08 (-0.14;-0.01), P=0.022. Serum INSL3, but not inhibin B or testosterone, was associated with testicular size in a multivariate linear regression, (B) (95%CI); 4.7 (0.5 ; 8.9), P=0.030. Conclusions Serum INSL3 is reduced years following AAS cessation in men, independently of testosterone, suggesting persistently impaired Leydig cell capacity.