The therapeutic role of gonadotropins in male factor infertility—a narrative review
Year: 2026
Type: review
Abstract: Background and Objective: 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. Methods: 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. Key Content and Findings: 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. Conclusions: 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.
Institutions: Imperial College Healthcare NHS Trust, Charing Cross Hospital
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223946153