When to use metformin or estrogen in Polycystic Ovary Syndrome (PCOS)?

From the Guidelines

Metformin is recommended for use in Polycystic Ovary Syndrome (PCOS) to improve menstrual cyclicity and hyperandrogenism, particularly in female individuals with type 2 diabetes, in addition to lifestyle modification.

Key Considerations

• The use of metformin in PCOS is supported by recent guidelines, including those from 2023 1 and 2024 1, which suggest its effectiveness in improving menstrual cyclicity and hyperandrogenism in female individuals with type 2 diabetes.
• Lifestyle modification is also emphasized as a crucial component of PCOS management, alongside metformin therapy.
• There is no direct mention of estrogen therapy in the provided evidence as a recommended treatment for PCOS, but oral contraceptive pills, which contain estrogen, are noted not to be contraindicated for female individuals with type 2 diabetes 1.
• Evaluation for PCOS in female adolescents with type 2 diabetes, including laboratory studies when indicated, is recommended 1.

Treatment Approach

• Metformin is likely to be beneficial for female individuals with PCOS and type 2 diabetes, aiming to improve menstrual cyclicity and hyperandrogenism.
• The decision to use metformin should be made on a case-by-case basis, considering the individual's overall health status, presence of type 2 diabetes, and specific symptoms of PCOS.
• Oral contraceptive pills may be considered for treating PCOS symptoms, especially for those without type 2 diabetes or other contraindications, but the provided evidence does not specify their use as a first-line treatment in the context of PCOS with type 2 diabetes.

The FDA Drug Labels for metformin (PO), estrogen (PO) do not address this question.

From the Research

Metformin in PCOS

• Metformin is used to manage polycystic ovary syndrome (PCOS) by ameliorating insulin resistance, which helps to resolve hormonal and metabolic disturbances and increases ovulation, pregnancy, and live birth rates relative to placebo 2.
• The use of metformin may prove beneficial in a subset of the population of women with PCOS, particularly those with hyperinsulinemia, as demonstrated by elevated insulin levels on a 2-hour 75-g load glucose tolerance test 3.
• Metformin can be beneficial in normalizing menstrual irregularities and stimulating ovulation in previously anovulatory women 4.
• Metformin is associated with a high incidence of gastrointestinal symptoms, but serious adverse effects are rare and there is no evidence of teratogenicity 5.

Estrogen in PCOS

• There is no mention of estrogen in the provided studies as a treatment for PCOS.

Combination Therapy

• A combination of metformin with clomifene citrate is more effective than either alone and is a useful option in women with clomifene-resistant PCOS 2.
• Combining metformin with letrozole is not more effective than letrozole alone 2.

Timing and Dosage

• Continuing metformin to the end of the 1st trimester at an effective dose (e.g. 1000-2000 mg/day) may help to reduce the rate of miscarriages 2.
• Further research is needed to define with greater precision the optimal dosage and times to initiate and discontinue metformin in women with PCOS who achieve pregnancy 2.