Impact of GLP-1 Receptor Agonists on Male Fertility: Emerging Evidence and Future Directions.

OBJECTIVE

To synthesize emerging mechanistic, preclinical, and clinical evidence evaluating the impact of GLP-1RAs on male fertility, including effects on testicular function, reproductive hormones, semen parameters, and sexual function.

METHODS

A comprehensive literature search was conducted across PubMed, MEDLINE, and Embase through May 31, 2025, identifying relevant preclinical and clinical studies examining GLP-1RAs and male reproductive health.

RESULTS

The search strategy identified 16 clinical studies meeting our inclusion criteria, and these studies were included in the summary tables for review. GLP-1 receptors are present in male reproductive tissues. Preclinical studies indicate GLP-1RAs enhance spermatogenesis, hormone profiles, and sperm function in obese/diabetic rodent models via cAMP/PKA and PI3K/Akt pathways. In vitro data show improved sperm motility and Sertoli cell metabolism with GLP-1RAs. Limited clinical studies suggest potential improvements in semen parameters and testosterone levels in obese hypogonadal men, though heterogeneous results highlight the need for further research.

CONCLUSION

GLP-1RAs likely have a beneficial effect on male fertility, particularly in the setting of metabolic dysfunction, but clinical evidence is limited. Larger prospective studies are needed to confirm safety and efficacy.