Serum insulin-like factor 3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose human chorionic gonadotropin: a randomized, controlled trial

Objective: To study the potential role for using serum biomarkers, including insulin-like factor 3 (INSL3), 17 alpha-hydroxyprogesterone, antimullerian hormone, and inhibin B, as correlates of intratesticular T (IT-T) concentrations in men. Design: Prospective, randomized, controlled trial. Setting: University-based medical center. Patient(s): Thirty-seven healthy men aged 18-50 years. Intervention(s): All men received the GnRH antagonist acyline, plus very low doses of hCG (0 IU, 15 IU, 60 IU, or 125 IU) SC every other day or 7.5 g T gel daily (75 mg delivered). The IT-T concentrations obtained by percutaneous testicular aspiration with simultaneous serum protein and steroid concentrations were measured at baseline and after 10 days of treatment. Main Outcome Measure(s): Intratesticular and serum hormone and gonadotropin concentrations. Result(s): After 10 days of gonadotropin suppression, serum INSL3 decreased by more than 90% and correlated highly with IT-T concentrations. In contrast, serum inhibin B, antimullerian hormone, and 17 alpha-hydroxyprogesterone did not correlate with IT-T. Serum INSL3 increased with the dose of hCG administered and returned to baseline after treatment. Conclusion(s): Serum INSL3 correlates highly with IT-T and serum T concentrations during acute gonadotropin suppression in men. Human chorionic gonadotropin stimulates dose-dependent increases in INSL3 and IT-T in healthy men and might be a useful biomarker of IT-T concentration in some clinical settings. Clinical Trial Registration Number: NCT# 00839319. (Fertil Steril (R) 2013;99:132-9. (C) 2013 by American Society for Reproductive Medicine.)