Metabolic Reversal of Functional Hypogonadism? GLP-1 Receptor Agonists and Male Reproductive Endocrinology-A...

Testosterone deficiency is highly prevalent in men with obesity and type 2 diabetes mellitus and often reflects functional suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in these conditions, but their effects on male reproductive endocrinology remain incompletely defined.

To systematically review the effects of GLP-1 receptor agonists on testosterone, HPG axis hormones, and male reproductive outcomes.

A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Cochrane, and Google Scholar were searched (January 2021-January 2026) for studies evaluating GLP-1 RA therapy in adult men with reported endocrine or reproductive outcomes.

Eight studies met inclusion criteria, including one randomised placebo-controlled crossover trial and six observational or interventional studies. In men with obesity, type 2 diabetes, or functional hypogonadism, GLP-1 RAs were associated with modest increases in testosterone and improvements in erectile function or selected semen parameters. In contrast, a placebo-controlled trial in healthy eugonadal men showed no significant endocrine or reproductive effects. Responses appeared dependent on baseline metabolic status.

GLP-1 RAs are associated with improvements in male reproductive endocrinology in metabolically compromised populations with metabolic hypogonadism while remaining neutral in healthy individuals. Larger prospective studies are needed.