Effects of glucagon-like peptide-1 receptor agonists on male reproductive hormones, semen parameters, and metabolic outcomes: a systematic review.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are antidiabetic agents that also induce weight loss. Their widespread use has prompted investigation of potential benefits beyond glycemic control, including effects on male sexual and reproductive function. Emerging evidence suggests that they may improve male reproductive parameters, particularly in men with metabolic dysfunction. OBJECTIVES: To systematically evaluate the effects of GLP-1RAs (liraglutide, semaglutide, dulaglutide, and exenatide) on male reproductive hormones, semen parameters, and metabolic outcomes. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched in PubMed, Embase, Scopus, and Web of Science up to April 2025. Eligible studies included randomized controlled trials (RCTs) and cohort studies evaluating the effects of GLP-1RAs in adult men. Assessed the risk of bias with the risk of bias 2 tool for RCT and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool for observational studies. RESULTS: Ten studies involving a total of 639 men were included. GLP-1RAs were consistently associated with increased total testosterone, particularly in men with obesity, type 2 diabetes, or functional hypogonadism. Free testosterone changes were inconsistent, often offset by concurrent rises in sex hormone-binding globulin. Luteinizing hormone and follicle-stimulating hormone levels were preserved or increased with GLP-1RA use, in contrast to the suppression observed in testosterone therapy comparator groups. Improvements in semen parameters were reported in obese or hypogonadal men; however, no significant changes were found in healthy individuals. CONCLUSION: GLP-1RAs may improve testosterone levels and potentially enhance semen quality in men with metabolic issues, while maintaining gonadotropin function. They could serve as fertility-sparing alternatives to testosterone therapy in some obesity-related hypogonadism cases. More long-term, controlled studies with standardized fertility measures are needed to confirm their role in male reproductive health.