The Impact of GLP-1 Receptor Agonists on Semen Parameters and the Hypothalamic–Pituitary–Gonadal Axis in Men with Obesity — A Literature Review

Abstract

Background. Rising global obesity prevalence has coincided with a debated decline in semen quality. GLP-1 receptor agonists (GLP-1 RAs) are now widely used for weight reduction in men of reproductive age, raising questions about their effect on fertility, particularly relative to testosterone replacement therapy (TRT), which suppresses spermatogenesis. Aim. To review evidence on GLP-1 RAs and the male reproductive system, focusing on semen parameters and the hypothalamic-pituitary-gonadal axis, and whether effects are drug-specific or mediated by weight loss. Material and methods. Narrative review of PubMed, Scopus and Web of Science on GLP-1 RAs, semen quality, male fertility, testosterone, functional hypogonadism, obesity and weight loss, with reference-list screening and ClinicalTrials.gov. English-language studies only; no time restriction. Results. GLP-1 receptors are expressed in human testis and spermatozoa. Obesity impairs semen quality via endocrine, inflammatory and thermal mechanisms. GLP-1 RAs raise testosterone while preserving gonadotropic function, unlike TRT; a randomized trial showed semaglutide improved sperm morphology while testosterone worsened sperm count. Weight loss, not the drug itself, appears the principal mediator, as exercise gave comparable benefit to liraglutide. Bariatric surgery did not reliably improve semen quality. Sexual-function data remain conflicting. Evidence is limited by small samples and short follow-up. Conclusions. GLP-1 RAs appear reproductively safe and may improve semen parameters in men with obesity-related functional hypogonadism, offering a fertility-sparing alternative to TRT. Benefit is largely attributable to weight loss; lifestyle intervention remains reasonable first-line. Larger, longer trials, including tirzepatide, are needed.