GLP-1 Therapy and Reproductive Health: What Prescribers Need to Know

A significant proportion of patients seeking GLP-1 weight management therapy are women of reproductive age. For prescribers, understanding the implications of GLP-1 therapy for reproductive health — including fertility, pregnancy, and conditions like PCOS — is essential for safe and effective prescribing.

Obesity is associated with reduced fertility in both women and men. In women, obesity is associated with:

• Anovulation and irregular menstrual cycles
• Polycystic ovary syndrome (PCOS)
• Reduced IVF success rates
• Increased miscarriage risk

Weight loss — regardless of how it is achieved — generally improves fertility outcomes in obese women. GLP-1 therapy, by producing significant weight loss, may improve fertility as a secondary effect.

Beyond weight loss, GLP-1 receptors are expressed in reproductive tissues, including the ovaries and uterus. Research has examined whether GLP-1 agonism has direct effects on reproductive function:

Ovarian function: Some research suggests GLP-1 agonists may improve ovarian function in women with PCOS, independent of weight loss effects.

Endometrial function: GLP-1 receptors are expressed in the endometrium. The clinical significance of this is not fully established.

Male fertility: GLP-1 receptors are expressed in testicular tissue. Some research suggests GLP-1 agonists may improve sperm parameters in obese men, though the data is limited.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10% of women. PCOS is characterized by:

• Hyperandrogenism
• Ovulatory dysfunction
• Polycystic ovarian morphology

Insulin resistance is a key feature of PCOS in many patients. GLP-1 agonists, which improve insulin sensitivity and promote weight loss, have been studied as a treatment for PCOS.

Evidence: Multiple studies have shown that GLP-1 agonists improve menstrual regularity, reduce androgen levels, and improve metabolic parameters in women with PCOS. A 2024 meta-analysis found that GLP-1 agonists significantly improved menstrual regularity and reduced testosterone levels in women with PCOS.

Clinical implication: GLP-1 therapy may be particularly beneficial for overweight or obese women with PCOS who want to improve both metabolic health and reproductive function.

All GLP-1 receptor agonists are labeled as Pregnancy Category C (risk cannot be ruled out) or equivalent. The FDA recommends discontinuing GLP-1 therapy at least 2 months before a planned pregnancy.

Animal studies have shown adverse effects on fetal development with GLP-1 agonists at doses above the human therapeutic range. These effects include:

• Reduced fetal weight
• Skeletal abnormalities
• Increased fetal mortality

Human data on GLP-1 therapy in pregnancy is limited. There are case reports and small observational studies, but no randomized controlled trials. The available data does not show a clear signal of teratogenicity, but the data is insufficient to establish safety.

GLP-1 agonists slow gastric emptying, which can affect the absorption of oral contraceptives. This interaction is clinically relevant:

• Oral contraceptives should be taken at least 1 hour before or 4 hours after GLP-1 injection
• Alternatively, consider non-oral contraceptive methods for patients on GLP-1 therapy

This is a critical counseling point: Patients who are not aware of this interaction may have reduced contraceptive efficacy.

For every patient of reproductive age starting GLP-1 therapy:

1. Discuss pregnancy plans: Ask about current and planned pregnancy
2. Counsel on discontinuation: Recommend discontinuing GLP-1 therapy at least 2 months before attempting conception
3. Counsel on contraception: Discuss the oral contraceptive interaction and ensure patients have reliable contraception
4. Counsel on fertility effects: Inform patients that weight loss may improve fertility — some patients may become pregnant unexpectedly
5. Document the counseling: Document this discussion in the medical record

If a patient becomes pregnant while on GLP-1 therapy:

1. Discontinue GLP-1 therapy immediately
2. Refer to obstetrics for pregnancy management
3. Report the pregnancy to the manufacturer's pregnancy registry (if available)
4. Document the exposure and the actions taken

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This content is for informational and educational purposes only. It does not constitute medical advice. Prescribers should review current prescribing information and use clinical judgment.