Serum INSL3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low dose hCG A randomized controlled trial

Serum INSL3 correlates with intratesticular testosterone during hCG administration. Measurement of serum INSL3 may be a useful biomarker of intratesticular testosterone during hCG treatment of infertile men.

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Mara Y. Roth, M.D., Kat Lin, M.D., M.Sc., Ph.D., John K. Amory, M.D., M.P.H., Bradley D. Anawalt, M.D., Alvin M. Matsumoto, M.D., Brett T. Marck, B.S., William J. Bremner, M.D., Ph.D., Stephanie T. Page, M.D., Ph.D.

Volume 99, Issue 1, Pages 132-139, January 2013



To study the potential role for using serum biomarkers including insulin-like factor 3 (INSL3), 17-hydroxyprogesterone (17-OHP), anti-Mϋllerian hormone (AMH) and inhibin B (INHB) as correlates of intratesticular testosterone (IT-T) concentrations in men.


Prospective, randomized, controlled trial.


University-based medical center.


Thirty-seven healthy men aged 18-50 years.


All men received the gonadotropin-releasing hormone antagonist, acyline, plus very low doses of human chorionic gonadotropin (hCG) (0 IU, 15 IU, 60 IU or 125 IU) subcutaneously every other day or 7.5 grams testosterone gel daily (7.5 mg delivered). 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 Measures:

Intratesticular and serum hormone and gonadotropin concentrations.


Following 10 days of gonadotropin suppression, serum INSL3 decreased by over 90% and correlated highly with IT-T concentrations. In contrast, serum INHB, AMH and 17-OHP did not correlate with IT-T. Serum INSL3 increased with the dose of hCG administered and returned to baseline after treatment.


Serum INSL3 correlates highly with IT-T and serum testosterone concentrations during acute gonadotropin suppression in men. HCG stimulates dosedependent 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

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.