Author: John David Gordon MD
Last week Laurie Wood joined me on Talk Fertility, our Facebook Friday feature here at Southeastern Fertility. Laurie provided me some very helpful insight into the use of the idiom “Bless your little heart…” Now I am going to constantly wonder if I am being dissed by my staff when they utter these words…But I guess that is really up to me to figure out.
So after Laurie schooled me in various terms including “f-u-r” as in “my home is fur away from here,” I shared with her the correct Boston-based pronunciation of pharmacy (fahm-missy) and sent her on her way. This served as my transition into a discussion about Polycystic Ovarian Syndrome (PCOS). During my exposition I touched on the use of metformin or Glucophage and some patients were left wondering why they should take a medication for diabetes when they have a fertility issue. The answer lies in the data which suggests that PCOS is actually intimately related to insulin resistance.
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 1000 mg; after another week, the dose is increased to the maximum of 1500 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 or letrozole 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 letrozole or clomiphene if a women fails to resume regular menstrual cycles.