Treatment of Polycystic Ovarian Syndrome (PCOS)

by

Dr. Timea Belej-Rak

Summer 2008

PCOS or PolyCystic Ovarian Syndrome is the most common cause of menstrual irregularity and affects 5-10% of reproductive age women. The diagnostic criteria were revised in 2003 in Rotterdam, and include two out of the three following symptoms:

 

1. Chronic anovulation (lack of ovulation, as evidenced by irregular periods);

2. Clinical (acne, excess hair, oily skin, thickened skin, male pattern balding) or biochemical   signs of hyperandrogenism (elevated levels of male hormones, or androgens);

3. Polycystic ovaries on ultrasound.

 

Other causes of these symptoms must also be ruled out before the PCOS is diagnosed. It is important to realize that about 20% of reproductive age women have polycystic ovaries on ultrasound. This may be reflective of an excellent ovarian reserve, meaning there are a lot of potential eggs or follicles in the ovaries. It does not necessarily mean that they have PCOS, the syndrome.

 

The underlying mechanism in PCOS involves the cells within the ovary being able to produce more of the male hormones, which then lead to the clinical symptoms described above. Insulin has recently been found to be involved in this mechanism, but according to the Rotterdam consensus, no insulin testing is needed to establish the diagnosis of PCOS. The long-term health risks associated with PCOS include obesity (30% of patients), development of Type II diabetes, heart disease and endometrial cancer (if there are prolonged times without a period). A sugar drink test (oral glucose tolerance test) and a check of the cholesterol levels are recommended in patients with obesity.

 

Lifestyle modifications. Diet and exercise have been shown to be extremely effective in preventing the development of diabetes, even better than anti-diabetic medication. Several studies have shown that in obese PCOS patients, weight loss of as little as 5% body weight helped restore periods and up to 40% of patients achieved pregnancy. Obesity is also associated with a lower response to treatment, an increased risk of pregnancy loss and pregnancy complications, such as pre-eclampsia/toxemia and gestational diabetes, among others.

 

Clomiphene citrate (CC). CC has been and remains the first drug of choice for ovulation induction in anovulatory women with PCOS. Ovulation is achieved in 75-80% of patients, with pregnancy rates of up to 20% per ovulatory cycle. The usual length of treatment is 6 cycles, though in some cases therapy may be extended for up to one year. Side effects of CC include hot flashes, abdominal bloating, emotional effects, multiple pregnancy, ovarian cyst formation and thinning of the uterine lining (endometrium), among others.

 

Insulin sensitizing or anti-diabetic medications. Some women with PCOS have also been found to have insulin resistance. This is also found in Type II diabetes, and results from the body not being able to use insulin properly. In many cases of Type II diabetes, the pancreas produces enough insulin, but because of insulin resistance, sugar remains in the blood instead of being used as fuel. With the discovery of insulin resistance in PCOS, a new potential treatment option with anti-diabetic drugs (i.e. metformin) was explored. Initial studies were reassuring, but have also been clouded with controversy. Metformin is as effective in achieving ovulation as weight loss through lifestyle modifications. The only study to use live birth as an endpoint was published in February 2007 in the New England Journal of Medicine. It compared first-line metformin to CC to the combination of the two. The best outcome was in the CC group. There was no difference in miscarriage rates among the three groups. Side effects may include, but are not limited to abdominal bloating, nausea and diarrhea.

 

Metformin can be considered in certain situations, such as an abnormal result following the sugar drink test, with extreme obesity or if no ovulation was achieved with CC.

 

Gonadotropins. If ovulation cannot be achieved with the above-mentioned treatments, the alternative next step involves using injectable drugs called gonadotropins. They usually consist of FSH (follicle stimulating hormone, the same hormone your brain usually sends to the ovaries to tell them to make eggs) and are self-administered in daily injections. Pregnancy rates are up to 20% per cycle. Side effects include, but are not limited to minor discomfort from the injections, multiple pregnancy and emotional changes. Treatment beyond six cycles is usually not recommended.

 

Laparoscopic ovarian surgery (LOS)/ovarian drilling. Ovarian drilling is an outpatient day procedure performed by laparoscopy, where a 1 cm incision is made in or under the belly button, allowing a camera to be inserted, with two 5 mm incisions in the left and right lower quadrants. Four to ten punctures are then made in the ovaries. About 50% women will ovulate spontaneously following this procedure, while the rest may still require further treatment as described above. The risks include those of the procedure itself, in addition to adhesion (scar tissue) formation and potential loss of ovarian tissue. This technique may be considered in those who do not respond to CC, or instead of gonadotropins.

 

IVF (in vitro fertilization). IVF is usually indicated if there has been failure to achieve pregnancy with either CC, LOS or gonadotropins. There are suggestions in the literature that metformin in IVF may improve pregnancy rates and reduce the risk of ovarian hyperstimulation syndrome (when too many follicles or eggs are produced).

 

Some reports suggest that once patients with PCOS conceive, they may have higher rates of pregnancy complications, such as miscarriage, gestational diabetes, high blood pressure during pregnancy and smaller babies.

 

Women with PCOS may sometimes feel less feminine as a result of some of the associated symptoms, such as excess hair growth, irregular periods, obesity and infertility. Further negative feelings can be a result of poorer sexual self-worth and sexual satisfaction. Studies show that women with PCOS feel more depressed and anxious than those without the diagnosis. It is therefore important to address not only the medical, but also the emotional impact of PCOS during treatment.

The initial management of PCOS-related infertility involves first employing lifestyle changes, if obesity is a factor, and then moving to ovulation induction with CC. If ovulation is not achieved, then the next step is to move to injectable FSH or LOS. Finally, IVF can be considered if the aforementioned options have failed to result in pregnancy. The use of metformin in PCOS should be limited to women with an abnormal glucose tolerance test. Future studies include finding other classes of drugs for ovulation induction that would be superior to current ones. Further research is needed to understand the role of obesity in the response to different treatment strategies. Genetic studies of PCOS are also under way.

 

Dr. Belej-Rak completed her medical school, Obstetrics/Gynecology residency and her fellowship in Gynecologic Reproductive Endocrinology & Infertility at the University of Toronto. Dr. Belej-Rak is a fellow of the Royal College of Surgeons of Canada (Ob/Gyn) and is a staff physician at LifeQuest Centre for Reproductive Medicine, in Toronto. She is a member of the Society of Obstetricians and Gynecologists of Canada, the Canadian Fertility and Andrology Society, the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology.

 

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