(368) Effects of GLP-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 they may improve male reproductive parameters, particularly in men with metabolic dysfunction. Objective 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 PRISMA guidelines. Databases searched included PubMed, Embase, Scopus, and Web of Science up to April 2024. Eligible studies reported GLP-1RA effects on testosterone (total/free), gonadotropins (LH, FSH), SHBG, semen quality, and metabolic markers in adult men. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for observational studies. Results Ten studies were included: Four randomized controlled trials, one crossover trial, and five cohort studies. 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 SHBG. Gonadotropin levels increased in some studies and remained stable in others, depending on comparator treatments. Improvements in semen motility, morphology, and concentration were reported in obese hypogonadal men but not in healthy individuals. All studies showed significant improvements in metabolic outcomes, including HbA1c and weight loss. Conclusions GLP-1RAs may improve testosterone levels, preserve gonadotropin function, and potentially enhance semen quality in metabolically impaired men. These agents represent a promising adjunct or alternative to testosterone therapy in selected patients. Further long-term, comparator-controlled trials with standardized reproductive endpoints are needed to establish their role in male reproductive health. Disclosure No