From the Guidelines
Metformin is recommended for patients with Polycystic Ovary Syndrome (PCOS) who have cardiometabolic features such as abdominal obesity and insulin resistance. The most recent and highest quality study, published in 2020 1, suggests that metformin is beneficial for PCOS patients with insulin resistance, as it improves insulin sensitivity, reduces glucose production in the liver, and enhances peripheral glucose uptake. This leads to several benefits, including decreased androgen levels, improved menstrual regularity and ovulation rates, modest weight loss support, and potentially reduced risk of developing type 2 diabetes.
Key Points
- Metformin is typically prescribed at 500-2000mg daily, starting at 500mg with meals and gradually increasing to minimize gastrointestinal side effects.
- The medication works by improving insulin sensitivity, reducing glucose production in the liver, and enhancing peripheral glucose uptake.
- For PCOS patients, metformin's effects translate to several benefits, including:
- Decreased androgen levels leading to reduced hirsutism and acne
- Improved menstrual regularity and ovulation rates
- Modest weight loss support
- Potentially reduced risk of developing type 2 diabetes
- Metformin may also enhance fertility outcomes when used alone or combined with clomiphene citrate for women trying to conceive.
- Common side effects include nausea, diarrhea, and abdominal discomfort, which often improve with continued use or extended-release formulations.
Considerations
- While metformin is not FDA-approved specifically for PCOS, its effectiveness is well-established, particularly for PCOS patients with insulin resistance, prediabetes, or those struggling with weight management 1.
- The 2020 study also highlights the importance of screening PCOS patients for cardiovascular disease risk, including close monitoring of weight changes, blood pressure, fasting lipid panel, and assessments for glycemic control 1.
From the Research
Role of Metformin in PCOS
- Metformin is widely used to manage type 2 diabetes and is commonly prescribed in polycystic ovary syndrome (PCOS) to address insulin resistance and associated metabolic and reproductive disturbances 2.
- The medication improves insulin resistance, menstrual regularity, and androgen levels, particularly in those with obesity or insulin resistance, and may enhance fertility when combined with other treatments 2, 3, 4.
Effects on Metabolic and Reproductive Outcomes
- Metformin induces higher glucose uptake, thus inducing a lower synthesis/secretion of insulin, which permits the possible restoration of the normal biological functions that are severely affected by the compensatory hyperinsulinemia reactive to the increased peripheral insulin resistance 3.
- It improves the impairments typically observed in hyperinsulinemic PCOS patients, reducing the possible evolution towards metabolic syndrome and Type 2 diabetes 3, 5.
- Metformin is an effective ovulation induction agent for non-obese women with PCOS and offers some advantages over other first line treatments for anovulatory infertility such as clomiphene 4.
Pregnancy-Related Outcomes
- Metformin may reduce early pregnancy loss, miscarriage, and preterm birth, though findings for gestational diabetes and preeclampsia are inconsistent 2, 6.
- It consistently reduces the risk of gestational diabetes, eclampsia, and hypertension when pregnancy occurs 3.
Limitations and Future Research
- Evidence is limited by study heterogeneity, varying diagnostic criteria, and the use of aggregate data in meta-analyses, all of which make interpretation challenging 2.
- Future research should prioritise well-powered clinical trials, individual patient data meta-analyses, and longer-term follow-up studies, particularly in pregnancy, to better define the populations most likely to benefit from metformin use across the PCOS spectrum 2.