Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study

Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materia...

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Main Authors: I-Shen Huang, Li-Hua Li, Wei-Jen Chen, Chi-Chang Juan, William J. Huang
Format: Article
Language:English
Published: Korean Society for Sexual Medicine and Andrology 2025-01-01
Series:The World Journal of Men's Health
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author I-Shen Huang
Li-Hua Li
Wei-Jen Chen
Chi-Chang Juan
William J. Huang
author_facet I-Shen Huang
Li-Hua Li
Wei-Jen Chen
Chi-Chang Juan
William J. Huang
author_sort I-Shen Huang
collection DOAJ
description Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions: The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.
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publishDate 2025-01-01
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spelling doaj-art-7835a14e4e02446b9f09daba1603474d2025-01-03T03:23:21ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-01-0143114215310.5534/wjmh.230265Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot StudyI-Shen Huang0https://orcid.org/0000-0003-1669-779XLi-Hua Li1https://orcid.org/0000-0002-2501-0913Wei-Jen Chen2https://orcid.org/0000-0002-0199-7602Chi-Chang Juan3https://orcid.org/0000-0001-5935-6675William J. Huang4https://orcid.org/0000-0002-0113-1307Department of Urology, Taipei Veterans General Hospital, Taipei, TaiwanDepartment of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, TaiwanDepartment of Urology, Taipei Veterans General Hospital, Taipei, TaiwanDepartment of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDepartment of Urology, Taipei Veterans General Hospital, Taipei, TaiwanPurpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions: The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.azoospermiaextracellular fluidinfertility; malesperm retrievaltestistestosterone
spellingShingle I-Shen Huang
Li-Hua Li
Wei-Jen Chen
Chi-Chang Juan
William J. Huang
Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
The World Journal of Men's Health
azoospermia
extracellular fluid
infertility; male
sperm retrieval
testis
testosterone
title Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
title_full Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
title_fullStr Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
title_full_unstemmed Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
title_short Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
title_sort intratesticular testosterone and its precursors among azoospermic men a pilot study
topic azoospermia
extracellular fluid
infertility; male
sperm retrieval
testis
testosterone
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