The therapeutic role of gonadotropins in male factor infertility-a narrative review.
- 1Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK.
Abstract
A male factor is contributory in up to 50% of infertility cases, with a rising global prevalence. Gonadotropins are the principal endocrine effectors of the hypothalamic-pituitary-gonadal (HPG) axis, driving spermatogenesis via luteinising hormone (LH)-mediated Leydig cell testosterone production and follicle-stimulating hormone (FSH)-mediated Sertoli cell support. Their therapeutic role spans hypogonadotropic hypogonadism (HH), iatrogenic gonadotropin suppression, idiopathic male infertility (iMFI), and non-obstructive azoospermia (NOA). Evidence strength varies considerably across these indications. This review aims to provide a comprehensive overview of the clinical evidence underpinning gonadotropin therapy across these aetiologies. A narrative review was conducted using PubMed, Embase and the Cochrane Library supplemented by the current European Association of Urology (EAU) and American Urological Association/American Society for Reproductive Medicine (AUA/ASRM) guidance, covering January 2000 to June 2026. Evidence was synthesised narratively. In HH, the indication is well established, with a recent systematic review and meta-analysis of 1,583 patients demonstrating a pooled spermatogenesis induction rate of 74% and an overall pregnancy rate of 52%. Sequential treatment commencing with human chorionic gonadotropin (hCG) monotherapy, followed by the addition of FSH where required, is endorsed by both the EAU [2026] and AUA/ASRM [2024] guidelines. Baseline testicular volume, serum inhibin B, and anti-Müllerian hormone have emerged as clinically useful predictors of treatment response. In iatrogenic HH arising from exogenous testosterone or anabolic steroid use, emerging evidence supports gonadotropin-mediated spermatogenic restoration, including in men who are unable or unwilling to discontinue androgen use. For iMFI, FSH therapy demonstrates a modest benefit, though heterogeneity in response attributable to FSH receptor (FSHR) mutations and histopathological subtype limits its routine application. In NOA, pre-operative gonadotropin stimulation prior to microsurgical testicular sperm extraction (mTESE) has shown variable outcomes, and the current available evidence remains insufficient to support a strong guideline recommendation. Gonadotropin therapy has a favourable safety profile with injection-site reaction and gynaecomastia the principal considerations. Gonadotropin therapy is an effective therapy for men with HH seeking paternity but remains limited in idiopathic infertility and NOA. Pharmacogenomic stratification and predictive biomarker integration are promising directions for individualising treatment and informing future research priorities.
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BibTeX
@article{patel2026therapeutic,
title = {{The therapeutic role of gonadotropins in male factor infertility-a narrative review.}},
author = {Minesh Patel and Amr Serage and Hassan Al Dehneen and Peter Grice and Suks Minhas},
journal = {Translational andrology and urology},
year = {2026},
month = oct,
doi = {10.21037/tau-2026-0682},
url = {https://europepmc.org/article/MED/42997202},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - The therapeutic role of gonadotropins in male factor infertility-a narrative review.
AU - Minesh Patel
AU - Amr Serage
AU - Hassan Al Dehneen
AU - Peter Grice
AU - Suks Minhas
PY - 2026
DA - 2026/10/22
JO - Translational andrology and urology
DO - 10.21037/tau-2026-0682
UR - https://europepmc.org/article/MED/42997202
AB - A male factor is contributory in up to 50% of infertility cases, with a rising global prevalence. Gonadotropins are the principal endocrine effectors of the hypothalamic-pituitary-gonadal (HPG) axis, driving spermatogenesis via luteinising hormone (LH)-mediated Leydig cell testosterone production and follicle-stimulating hormone (FSH)-mediated Sertoli cell support. Their therapeutic role spans hypogonadotropic hypogonadism (HH), iatrogenic gonadotropin suppression, idiopathic male infertility (iMFI), and non-obstructive azoospermia (NOA). Evidence strength varies considerably across these indications. This review aims to provide a comprehensive overview of the clinical evidence underpinning gonadotropin therapy across these aetiologies. A narrative review was conducted using PubMed, Embase and the Cochrane Library supplemented by the current European Association of Urology (EAU) and American Urological Association/American Society for Reproductive Medicine (AUA/ASRM) guidance, covering January 2000 to June 2026. Evidence was synthesised narratively. In HH, the indication is well established, with a recent systematic review and meta-analysis of 1,583 patients demonstrating a pooled spermatogenesis induction rate of 74% and an overall pregnancy rate of 52%. Sequential treatment commencing with human chorionic gonadotropin (hCG) monotherapy, followed by the addition of FSH where required, is endorsed by both the EAU [2026] and AUA/ASRM [2024] guidelines. Baseline testicular volume, serum inhibin B, and anti-Müllerian hormone have emerged as clinically useful predictors of treatment response. In iatrogenic HH arising from exogenous testosterone or anabolic steroid use, emerging evidence supports gonadotropin-mediated spermatogenic restoration, including in men who are unable or unwilling to discontinue androgen use. For iMFI, FSH therapy demonstrates a modest benefit, though heterogeneity in response attributable to FSH receptor (FSHR) mutations and histopathological subtype limits its routine application. In NOA, pre-operative gonadotropin stimulation prior to microsurgical testicular sperm extraction (mTESE) has shown variable outcomes, and the current available evidence remains insufficient to support a strong guideline recommendation. Gonadotropin therapy has a favourable safety profile with injection-site reaction and gynaecomastia the principal considerations. Gonadotropin therapy is an effective therapy for men with HH seeking paternity but remains limited in idiopathic infertility and NOA. Pharmacogenomic stratification and predictive biomarker integration are promising directions for individualising treatment and informing future research priorities.
SN - 2223-4691
ER -