From the Guidelines
Metformin can help restore ovulation in women with polycystic ovary syndrome (PCOS) who experience anovulation, although its effects on early pregnancy are not well understood 1.
Key Points to Consider
- The American College of Obstetricians and Gynecologists (ACOG) recommends clomiphene citrate as the first-line treatment for ovulation induction in women with PCOS due to its effectiveness, with about 80% of women ovulating and half of them conceiving 1.
- Metformin improves the frequency of ovulation but its impact on pregnancy outcomes is not clearly defined, making it a secondary option for ovulation induction 1.
- The typical starting dose of metformin is 500 mg once daily with a meal, gradually increasing to 1500-2000 mg daily in divided doses to minimize gastrointestinal side effects.
- Treatment with metformin usually continues for at least 3-6 months to evaluate its effectiveness for ovulation induction.
Mechanism of Action and Side Effects
- Metformin works by reducing insulin resistance, which is common in PCOS and contributes to elevated androgen levels that disrupt normal ovarian function 1.
- By improving insulin sensitivity, metformin helps lower androgen production, normalize hormone levels, and restore regular menstrual cycles and ovulation.
- Common side effects of metformin include nausea, diarrhea, and abdominal discomfort, which typically improve over time.
Considerations for Conception and Pregnancy
- For women actively trying to conceive, metformin is generally considered safe during pregnancy, though patients should discuss continuation with their healthcare provider once pregnancy is confirmed.
- It is essential to note that while metformin may help restore ovulation, its primary use is for managing type 2 diabetes, and its effects on pregnancy, especially in the context of PCOS, require careful monitoring 1.
From the FDA Drug Label
Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin hydrochloride tablets may result in ovulation in some anovulatory women. Metformin may result in ovulation in some anovulatory women.
- The drug label advises discussing the potential for unintended pregnancy with premenopausal women taking metformin hydrochloride tablets 2.
From the Research
Metformin and Ovulation
- Metformin may improve live birth rates compared with placebo in women with polycystic ovary syndrome (PCOS) 3
- The use of metformin is associated with higher rates of gastrointestinal side effects, such as nausea and diarrhea 3, 4
- Metformin may be beneficial in combination with clomiphene citrate (CC) for ovulation induction, but the evidence is uncertain 3, 5
- Letrozole may be more effective than metformin and CC combined for inducing ovulation in women with CC-resistant PCOS 6
Effects of Metformin on Ovulation and Pregnancy
- Metformin may improve ovulation rates and clinical pregnancy rates compared with placebo 3, 4
- The combination of metformin and CC may be more effective than either treatment alone for ovulation induction and clinical pregnancy rates 3, 5
- Metformin may reduce the risk of miscarriage when continued until the end of the first trimester 4
Comparison of Metformin with Other Treatments
- Clomiphene citrate may be more effective than metformin as a first-line treatment for ovulation induction in women with PCOS 5
- Letrozole may be more effective than metformin and CC combined for inducing ovulation in women with CC-resistant PCOS 6
- The optimal dosage and duration of metformin therapy for ovulation induction and pregnancy achievement are uncertain and require further research 4, 7