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

Abstract

Growing numbers of international guidelines recommend hormonal treatment for normogonadotropic men with abnormal semen parameters, despite uncertain effects on fertility outcomes. Evaluate the efficacy of hormonal treatment, compared with placebo or no treatment, in normogonadotropic men with abnormal semen parameters. We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and CENTRAL to February 2025. 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. 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. 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. 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.