The effectiveness of hormonal treatment to improve reproductive outcomes in normo-gonadotropic men with abnormal semen parameters: Results of two linked systematic reviews.

CONTEXT: Growing numbers of international guidelines recommend hormonal treatment for normogonadotropic men with abnormal semen parameters, despite uncertain effects on fertility outcomes. OBJECTIVE: Evaluate the efficacy of hormonal treatment, compared with placebo or no treatment, in normogonadotropic men with abnormal semen parameters. DATA SOURCES: We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and CENTRAL to February 2025. STUDY SELECTION: Two linked reviews were conducted simultaneously. Review 1 included randomised and non-randomised controlled studies evaluating hormonal treatments in normogonadotropic men with abnormal semen parameters. Review 2 included the same treatments in men undergoing assisted reproduction. All citations were double-screened. DATA EXTRACTIO: n Primary outcomes were changes in semen quality (in Review 1) and pregnancy (in Review 2). Risk of bias of the included studies was assessed using the Cochrane tool and ROBUST-RCT. Random-effects meta-analyses were performed. DATA SYNTHESIS: Nine studies (735 men) were included. Follicle-stimulating hormone (FSH) showed modest improvements in sperm count (Mean Difference [MD] 11.0, 95% confidence interval [CI] 7.2, 14.8), concentration (MD 5.6, 95% CI 1.9, 9.3) and motility (MD 3.4, 95% CI 0.7, 6.0) but not morphology (MD 4.7, 95% CI -0.8, 10.3). Studies of combined human chorionic and menopausal gonadotropins, as well as tamoxifen, showed no benefit. Two small studies reported non-significant increases in pregnancy with FSH. No eligible studies evaluated aromatase inhibitors or clomiphene. CONCLUSIONS: We cautiously report potential for selective use of FSH in normogonadotropic men. However, the expected benefits are modest and short-term, with uncertain translation to pregnancy or live birth.