Serum insulin-like factor 3 levels are reduced in former androgen users suggesting impaired Leydig cell capacity
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.
Jon Jarløv Rasmussen, MD, PhD, Jakob Albrethsen, PhD, Mikkel Nicklas Frandsen, BSc, Niels Jørgensen, MD, PhD, Anders Juul, MD, PhD, DMSc, Caroline Kistorp, MD, PhD, Serum insulin-like factor 3 levels are reduced in former androgen users suggesting impaired Leydig cell capacity, The Journal of Clinical Endocrinology & Metabolism, 2021;, dgab129, Serum insulin-like factor 3 levels are reduced in former androgen users suggesting impaired Leydig cell capacity
