Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for metabolic disorders; however, their effects on male reproductive hormones and semen quality remain insufficiently characterized. We hypothesized that glucagon-like peptide-1 receptor agonists (GLP-1RAs) positively influence male reproductive hormonal profiles and semen parameters, in addition to their established metabolic benefits. The aim of this study was to systematically evaluate the effects of liraglutide, semaglutide, and dulaglutide on testosterone levels, gonadotropins, SHBG, and semen quality in adult men.

We conducted a systematic review following PRISMA guidelines. We systematically searched PubMed, Embase, Scopus, and Web of Science up to April 2024. We evaluated the effects of glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and dulaglutide) compared to placebo, testosterone therapy, metformin, or other active treatments on male reproductive hormones (total testosterone, free testosterone, luteinizing hormone [LH], follicle-stimulating hormone [FSH], sex hormone-binding globulin [SHBG]) and semen parameters (volume, concentration, motility, morphology).

A total of seven studies involving 371 participants were included. GLP-1RA therapy was associated with significant increases in total testosterone concentrations, particularly among obese men and individuals with metabolic dysfunction. Improvements in LH, FSH, and SHBG levels were observed with liraglutide, whereas semaglutide demonstrated stability of gonadotropin levels. Semen quality was improved by increasing sperm concentration, total sperm count, motility, and the proportion of morphologically normal sperm, particularly in obese men. In contrast, testosterone therapy significantly impaired spermatogenesis by reducing sperm concentration and total sperm count. GLP-1RAs also improved fasting glucose and HbA1c concentrations.

The results suggest that GLP-1 receptor agonists improve male reproductive endocrine function, particularly in obese and metabolically compromised men. Treatment with GLP-1RAs led to increases in total testosterone concentrations and favorable changes in gonadotropin secretion, notably with liraglutide. Improvements in semen parameters, including sperm concentration, total sperm count, motility, and morphology, further support a positive impact on spermatogenesis. Improvements in glycemic control may have contributed to these reproductive benefits. In contrast, testosterone replacement therapy adversely affected spermatogenesis by suppressing endogenous sperm production.

GLP-1 receptor agonists represent a promising therapeutic strategy for improving both reproductive and metabolic health in obese and metabolically compromised men. Treatment with GLP-1RAs was associated with favorable changes in reproductive hormonal profiles, enhancements in semen quality, and significant improvements in metabolic parameters. These findings support the potential role of GLP-1 receptor agonists in the management of male reproductive dysfunction associated with metabolic disorders.