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

Zafrani Z, Khan SS, Zitzmann M

Cells, 2026

Abstract

Background: 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.

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

Methods: 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.

Results: 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.

Conclusions: GLP-1 RAs are associated with improvements in male reproductive endocrinology in metabolically compromised populations with metabolic hypogonadism while remaining…

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