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

Manish Kuchakulla1, Phillip J Poppas2, Gal Wald1

  • 1Department of Urology, New York-Presbyterian Hospital, New York, NY; Department of Urology, Weill Cornell Medical Center, New York, NY.

Urology
|September 28, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise for improving male fertility, especially in metabolic dysfunction. Further clinical studies are needed to confirm their safety and effectiveness.

Area of Science:

  • Reproductive Endocrinology
  • Metabolic Health
  • Pharmacology

Background:

  • Glucagon-like peptide-1 receptors (GLP-1Rs) are present in male reproductive tissues.
  • Metabolic dysfunction, including obesity and diabetes, negatively impacts male reproductive health.
  • GLP-1 receptor agonists (GLP-1RAs) are established treatments for type 2 diabetes and obesity.

Purpose of the Study:

  • To synthesize evidence on the impact of GLP-1RAs on male fertility.
  • To evaluate effects on testicular function, reproductive hormones, semen parameters, and sexual function.
  • To assess GLP-1RA efficacy in preclinical and clinical settings.

Main Methods:

  • Comprehensive literature search of PubMed, MEDLINE, and Embase up to May 31, 2025.
  • Inclusion of preclinical and clinical studies examining GLP-1RAs and male reproductive health.
  • Summary tables for review of 16 identified clinical studies.

Main Results:

  • Preclinical studies in rodents show GLP-1RAs enhance spermatogenesis and sperm function via specific molecular pathways (cAMP/PKA, PI3K/Akt).
  • In vitro studies indicate improved sperm motility and Sertoli cell metabolism with GLP-1RAs.
  • Limited clinical data suggest potential improvements in semen parameters and testosterone in obese hypogonadal men, with heterogeneous outcomes.

Conclusions:

  • GLP-1RAs likely benefit male fertility, particularly in metabolic dysfunction.
  • Current clinical evidence is limited, necessitating further investigation.
  • Larger prospective studies are required to confirm GLP-1RA safety and efficacy in male reproductive health.

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