Polycystic Ovary Syndrome
Debra A. Minjarez M.D.

Introduction:

Polycystic ovary syndrome (PCOS) is a disorder affecting approximately 5-10% of reproductive age women and is the most common cause of infertility in women in the United States. Signs and symptoms include lack of ovulatory cycles, thus irregular periods and infertility, increased hair growth (hirsutism), acne and weight issues.
Laboratory evaluation may reveal elevated serum leutinizing hormone (LH), androgens such as testosterone and DHEAS, and hyperinsulinemia. Vaginal ultrasound may show enlarged ovaries with an increased number of small (6-10mm) follicles around the periphery. This classic appearance of polycystic ovaries, however, is not essential for the diagnosis of the syndrome. In fact 30% of PCOS patients may have normal appearing ovaries on ultrasound, while 25% of women with regular ovulatory cycles have PCO-like ovaries. Furthermore, 20-50% of women with PCOS are normal or below normal body mass index (BMI).

There is increasing data that insulin resistance is associated with elevated levels of androgens. High levels of androgen hormones then interfere with the normal hormone balance between the brain (pituitary) and ovary, leading to increased LH levels, anovulation, amenorrhea, and infertility.

In addition to the role insulin plays in ovulatory function, hyperinsulinemia has several long-term health consequences. Hyperinsulinemia has been associated with the development of high blood pressure, abnormal lipid levels, type II diabetes, and coronary artery disease. Several studies have identified hyperinsulinemia as a risk factor for breast, colon and rectal cancer. Consequently, every woman with PCOS should have a thorough evaluation and counseling before implementation of treatment.

Treatment:

With the development of a new group of medication known as insulin sensitizers there are now more treatment options available for PCOS patients. Multiple studies have validated that improving insulin sensitivity with Metformin or Troglitazone (Rezulin, has been withdrawn from the market because of hepatic failure), improves hyperandrogenism, induces ovulation and increases spontaneous pregnancy.

Clinical studies using Metformin have reported ovulatory response rates from 34-58%. Clomiphene citrate can then be used in Metformin treated patients who remain anovulatory, with an ovulatory response as high as 90%. Gastrointestinal symptoms, such as diarrhea, nausea, abdominal bloating and flatulence, are the most common reactions to Metformin. There have been no reported abnormalities associated with the use of Metformin during pregnancy in women with diabetes or PCOS women who have conceived during treatment. Despite the need to screen for insulin resistance, all PCOS patients attempting conception are candidates for Metformin. Studies have shown a beneficial effect in lean and obese PCOS patients independent of weight.

Several studies had proven Troglitzaone as an effective treatment modality in ovulation induction in PCOS patients. Since Troglitazones removal from the market, newer drugs, such as rosiglitazone and pioglitazone appear safer in terms of hepatoxicity, but are associated with embryotoxicity in animal studies. There are increasing studies using these newer classes of insulin sensitizers in the treatment of anovulation and dual therapy with Metformin for PCOS. Overall, great caution must be exercised with the use of these medications, as patients require frequent liver function monitoring.

PCOS patients who fail to ovulate to insulin sensitizers and clomiphene therapy can be treated with low dose human gonadotropins or in vitro fertilization (IVF). With low dose gonadotropin about 95% of patients will ovulate with a 55% cumulative pregnancy rate after six cycles. Once ovulation is achieved, approximately half will eventually conceive. Unfortunately, PCOS patients are at higher risk for ovarian hyperstimulation and multiple pregnancy rates of 20-30%.

For PCOS patients requiring IVF, stimulation protocols should be tailored to each individual patient to achieve a high probability of success and minimize the risk of ovarian hyperstimulation. Pretreatment with oral contraceptives and GnRH agonist allows improved stimulation leading to better oocyte quality, embryo development and excellent pregnancy rates in those patients who proceed directly into in vitro fertilization programs. 

For more information or a consult with Dr. Minjarez, please contact 303-355-2555.