Metformin and PCOS

Metformin and PCOS by: Ramaa P. Rao, MD

As a part of our continuing effort at FCI to keep our referring physicians informed of recent trends in reproductive medicine this monthly information letter will address the use of Metformin in patients with polycystic ovarian syndrome (PCOS).

PCOS is both an endocrine and metabolic disorder. The prevalence of PCOS is approximately 5-7% of women in the reproductive age group. Polycystic ovarian syndrome is characterized by Anovulation, hyperandrogenism, and polycystic-appearing ovaries on baseline Ultrasound. Many women with PCOS have insulin resistance defined as ratio of fasting glucose to insulin of less than 4.5. Both lean and obese women with PCOS can have insulin resistance. However, it is more common in obese hyperandrogenic women. There is strong evidence to support that lifestyle changes with low-carbohydrate diet, exercise, and weight loss reduce insulin resistance.

Clomiphene citrate has been a standard treatment for Ovulation Induction in polycystic-ovary patients for a long time. The live birth rate with Clomid is about 20%. The multiple pregnancy rate and risk of ovarian hyperstimulation increase significantly when gonadotropins are used after Clomid failure.

Recent clinical studies have shown that insulin sensitizers like Metformin increase the frequency of regular menstrual cycles and spontaneous Ovulation in PCOS patients. They have also been shown to improve the response to Clomid and Gonadotropin therapy in some patients. It is still controversial whether Clomid, Clomid plus FSH, or insulin sensitizers either used alone or in combination are a better option for PCOS patients.

Metformin is a Class-B drug. The recommended dose is 500 mg three times per day or 850 mg two times per day with meals. The most common gastrointestinal side-effects such as diarrhea, abdominal diarrhea and discomfort, nausea, and vomiting are dose-related. To reduce the side effects, treatment can be started with one dose of 500 mg with the largest meal and increased gradually at 7-10 day interval if the patient tolerates the medication. Metformin is contraindicated in patients with renal, hepatic, cardiovascular problems, and sepsis.

A rare but serious problem caused by Metformin is Lactic Acidosis. (1)The risk is increased in patients with creatinine over 1.4 mg/dl. 2)Approximately 10% of lactic acidosis occurs after IV administration of iodinated contrast material. Metformin should be stopped 48 hours before radiological procedures using iodinated contrast material. 3)Metformin should be stopped before surgical procedures that restrict fluid intake.

Based on this clinical evidence available to date, insulin sensitizers seem to offer a new additional treatment option for patients with PCOS.

We hope this information is helpful to your practice. I welcome any questions by you or your staff regarding this subject. Please call me directly at 630-889-7900. Thank you for your confidence in our practice and kind referrals to FCI.