The role of insulin resistance as the probable initiating factor in PCOS has important clinical implications. Because of the pioneering work done by Drs. John Nestler and Andrea Dunaif, the treatment of patients with PCOS has now shifted toward addressing the underlying issue of insulin resistance. Patients with PCOS are often treated with an insulin-sensitizing medication such as metformin (Glucophage). More than 20% of patients with PCOS and irregular cycles will experience a restoration of their normal cycles with metformin treatment. Because most patients who take metformin experience a diminished appetite, they may also benefit from weight loss with this therapy. Patients with PCOS also have increased rates of first-trimester miscarriage, and preliminary data suggest that there is a reduced rate of miscarriage in patients with PCOS who are treated with metformin.

In order to minimize the gastrointestinal side effects, the dose of metformin is increased gradually. Many physicians initially prescribe 500 mg a day of the extended release preparation of metformin, to be taken at dinner. After 1 week, the dose is increased to 1,000 mg; after another week, the dose is increased to the maximum of 1,500 mg. Most patients can tolerate the medication, although severe gastrointestinal side effects (mainly diarrhea) arise in 10% to 15% of patients. Patients who fail to resume predictable cycles with metformin therapy alone will need to consider ovulation induction with fertility medications.

The use of metformin as a first-line medication in the treatment of ovulation problems in patients with PCOS is controversial. Some physicians believe that clomiphene should be the first medication prescribed to women with PCOS who desire pregnancy and have irregular cycles. Our preference has been to start with metformin and then add clomiphene if a women fails to resume regular menstrual cycles.

Kristin comments:

My OB suggested I try metformin to regulate my cycles. I started on 500 mg and eventually went up to 1,000 mg—and it worked. I started to get regular periods. By charting my basal body temperature, I could tell that I was ovulating. I experienced major gastrointestinal issues with the drug, but they subsided after a month or so with some flare-ups on occasion. The side effects were worth it as far as I was concerned, especially if the metformin was going to help me get pregnant. When I started seeing an RE, my metformin dose was upped to 1,500 mg. Once I did get pregnant through IVF, I remained on metformin for the first trimester of my pregnancy.