(O-10) Impact of GLP-1 Receptor Agonists on Testosterone and Gonadotropin Profiles in Men: A Systematic Review

Abstract

Abstract Introduction Functional hypogonadism in men with obesity or type 2 diabetes mellitus (T2DM) is a common condition associated with low testosterone and impaired hormonal balance. GLP-1 receptor agonists (GLP-1RAs) are known to improve metabolic control, but their effects on reproductive hormones require further evaluation. To systematically review the effects of GLP-1RAs—liraglutide, semaglutide, and dulaglutide—on testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) in adult men. Methods Following PRISMA guidelines, we searched PubMed, Embase, Scopus, and Web of Science (inception–April 2024) for studies assessing GLP-1RA therapy effects on reproductive hormones. Eligible studies included RCTs, crossover trials, and cohort studies. Data on total/free testosterone, LH, FSH, and SHBG were extracted and analyzed. Results Six studies involving 315 men were included. Liraglutide increased total testosterone by 192.9% and SHBG by 157.1% in obese men with hypogonadism, alongside improvements in LH and FSH levels. Semaglutide stabilized gonadotropin levels without suppression and produced modest elevations in testosterone levels, though lower than those observed with testosterone therapy. Dulaglutide and short-term GLP-1 infusion in healthy, normal-weight men did not produce significant changes in testosterone or gonadotropins. When combined with metformin, GLP-1RAs increased total testosterone by 41.41 ng/dL and free testosterone by 0.44 ng/dL compared to metformin alone. Unlike exogenous testosterone therapy, GLP-1RAs preserved endogenous gonadotropin secretion. Conclusions GLP-1 receptor agonists appear to improve testosterone levels and restore gonadotropin function in men with obesity-related or functional hypogonadism. These agents offer a metabolic and endocrine advantage over conventional testosterone. Their dual role in metabolic and hormonal regulation supports their use in managing hypogonadism associated with metabolic disorders.