What is the role of metformin in the treatment of polycystic ovarian syndrome (PCOS)?

Updated: Sep 19, 2019
  • Author: Richard Scott Lucidi, MD, FACOG; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Answer

Metformin, an antidiabetic drug, improves insulin resistance and decreases hyperinsulinemia in patients with PCOS. [72] This drug also has a small but beneficial effect on metabolic syndrome, as well as potentially causing a modest reduction in androgen levels (11%). [5] Note that women with a body mass index (BMI) greater than 37 kg/m2 may not have a good response to metformin. [5] An Italian study of 33 patients with PCOS demonstrated that metformin affected thyroid hormone by lowering thyroid-stimulating hormone (TSH) in hypothyroid patients with PCOS, regardless of whether these individuals received levothyroxine or were untreated. [73]

Ascertain that kidney and liver function are normal and that the patient does not have advanced congestive heart failure before starting metformin therapy. The usual starting dose is 500 mg given orally twice a day. Because common adverse effects are nausea, vomiting, and diarrhea, metformin should be taken with meals. Patients who develop these adverse effects can be instructed to decrease the dosage to once a day for a week and then gradually increase the dosage. Also, inform patients that there is a high likelihood that they will have ovulatory cycles while taking metformin. The US Food and Drug Administration (FDA) has not approved metformin for this indication.

A secondary analysis of two randomized, double blind, placebo-controlled trials that included 182 children of mothers with PCOS reported that children exposed to metformin had higher BMI and increased prevalence of overweight/obesity at 4 years of age. The study found that at 4 years of age, the metformin group had higher weight z-score than the placebo group; difference in means 0.38 (0.07 to 0.69), p=0.017, and higher BMI z-score; difference in means 0.45 (0.11 to 0.78), p=0.010. There were also more overweight/obese children in the metformin group; 26 (32%) than in the placebo group; 14 (18%) at 4 years of age; odds ratio (95% CI): 2.17 (1.04 to 4.61), p=0.038. More studies are needed to examine this association. [74]


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