Serum insulin-like factor 3 levels are reduced in former androgen users suggesting impaired Leydig cell capacity

Serum insulin-like factor 3 levels are reduced in former androgen users suggesting impaired Leydig cell capacity / Jon Jarløv Rasmussen, Jakob Albrethsen, Mikkel Nicklas Frandsen, Niels Jørgensen, Anders Juul, Caroline Kistorp. - (The Journal of Clinical Endocrinology & Metabolism (2021) 9 March)

  • PMID: 33693710
  • DOI: 10.1210/clinem/dgab129


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.

Original document


Research / Study
9 March 2021
Albrethsen, Kakob
Frandsen, Mikkel Nicklas
Juul, Anders
Jørgensen, Niels
Kistorp, Caroline
Rasmussen, Jarløv
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International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)
Københavns Universitetshospital - Copenhagen University Hospital
Rigshospitalet - Danish National Hospital
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S1. Anabolic Agents
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15 March 2021
Date of last modification
18 March 2021
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