MON-157 - Effect of Glucagon Like Peptide-1 Agonist on Hypothalamo-Pituitary-Gonadal Axis in Males

Background: Obesity is increasingly prevalent and is strongly associated with dysregulation of the male hypothalamic pituitary gonadal (HPG) axis, functional hypogonadism and impaired semen quality. Glucagon like peptide 1 receptor agonists (GLP-1 RAs) are widely used for obesity and type 2 diabetes mellitus (T2DM), yet their effects on male reproductive hormones and fertility remain uncertain. This systematic review evaluated the impact of GLP-1 RAs on reproductive hormones, semen parameters and metabolic outcomes in men.

Methods: A systematic search of PubMed and the Cochrane Library identified randomised controlled trials (RCTs) involving men aged 18-65 years receiving a GLP-1 RA with appropriate comparators. Primary outcomes were total testosterone (TT), luteinising hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG); secondary outcomes included semen analysis, BMI, weight, lipids and HbA1c. Screening, data extraction and risk of bias assessment were performed independently by two reviewers. Where possible, mean changes and 95% confidence intervals were calculated, otherwise narrative synthesis was undertaken.

Results: Five RCTs met inclusion criteria. Two acute infusion studies of native GLP-1 in healthy men showed no meaningful changes in mean LH, FSH or TT, although one reported reduced testosterone pulse frequency without altered LH. A four-week dulaglutide crossover trial in healthy men found no significant changes in reproductive hormones, sexual function scores or semen quality, but demonstrated reduced HbA1c. In obese men with functional hypogonadism, a 16-week liraglutide trial showed significant increases in TT, LH and FSH and was superior to testosterone replacement therapy for overall health outcomes. A 24-week semaglutide trial showed improved sperm morphology and LDL cholesterol while preserving gonadotropins and TT. A Liraglutide weight-loss maintenance study reported improved sperm concentration and total count.

Conclusions: GLP-1 RAs do not appear to acutely suppress the male HPG axis and may improve reproductive hormones and semen parameters in obese hypogonadal men, largely within the context of weight loss. However, evidence remains limited and heterogeneous, underscoring the need for larger RCTs explicitly powered to assess male reproductive outcomes.

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