GLP-1 Receptor Agonists and Male Fertility: Current Evidence and Recommendations
GLP-1 receptor agonists have no demonstrated detrimental effects on male fertility, but should be discontinued at least 4 weeks before attempting conception as a precautionary measure based on limited human data. 1
Effects of GLP-1 Receptor Agonists on Male Reproductive Function
Current Evidence
- GLP-1 receptors are expressed in human testicular tissues, including Leydig cells, Sertoli cells, and germ cells 2
- Human sperm cells express GLP-1 receptors that affect sperm function and metabolism 3
- Recent research in mouse models showed that GLP-1 receptor agonists (liraglutide and semaglutide) had no detrimental effects on sperm concentration and motility 4
- Some evidence suggests GLP-1 receptor agonists may actually have positive effects on testicular function:
- Increase serum testosterone levels in men with functional hypogonadism related to diabetes/obesity
- Improve sperm metabolism and motility in vitro 2
Knowledge Gaps
The 2024 AUA/ASRM male infertility guidelines specifically note that "the effect of GLP-1 receptor agonists on reproductive health remains to be determined" 5. This highlights that while these medications are highly effective for treating obesity and type 2 diabetes, their specific impact on male fertility requires further investigation.
Recommendations for Men Planning Pregnancy
Pre-Conception Period
Discontinuation timing: Stop GLP-1 receptor agonists at least 4 weeks before attempting conception 1
- This recommendation is based on limited human data and serves as a precautionary approach
- The 4-week washout period allows for complete elimination of the medication from the body
Alternative management options:
- For men with type 2 diabetes: Consider transitioning to insulin or other diabetes medications with established safety profiles during the conception period
- For men using GLP-1 agonists for weight management: Focus on lifestyle modifications (diet and exercise) during the conception period
Fertility Preservation Considerations
For men with conditions requiring treatments that may affect fertility:
- Sperm banking should be planned before starting any potentially gonadotoxic treatments 5
- Semen cryopreservation with 1-3 samples is recommended 5
- There is no established role for hormonal or pharmacological gonadal protection in males 5
Special Considerations
Obesity and Male Fertility
Obesity itself negatively impacts male fertility through:
- Altered reproductive hormonal profiles
- Decreased sperm motility and morphology
- Reduced sexual function 6
Weight loss through GLP-1 receptor agonists may indirectly improve fertility parameters by addressing these obesity-related issues 6
Contraception During Treatment
- All pre-menopausal patients (and their male partners) undergoing systemic anti-cancer therapies should use active contraception
- This contraception should continue for 3-6 months following the last dose of therapy 5
Clinical Approach to GLP-1 Receptor Agonists in Men Planning Pregnancy
Assess fertility goals and timeline:
- For immediate conception plans: Discontinue GLP-1 receptor agonists at least 4 weeks before attempting conception
- For long-term planning: Continue GLP-1 therapy until ready to attempt conception
Weigh benefits vs. risks:
- Benefits of continuing therapy: Improved metabolic parameters, weight management
- Potential risks: Limited data on effects during conception period
- Consider that obesity itself negatively impacts fertility parameters
Monitor reproductive parameters:
- For men with concerns about fertility, consider semen analysis before and during GLP-1 therapy
- Track hormonal parameters if indicated (testosterone, FSH, LH)
Conclusion
While GLP-1 receptor agonists show promise for not negatively affecting male fertility (and potentially even improving some parameters), the cautious approach is to discontinue these medications at least 4 weeks before attempting conception until more definitive human data becomes available.