Polycystic Ovary Syndrome (PCOS)

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Polycystic ovary syndrome (PCOS), also called Stein-Leventhal Syndrome, is the most common endocrinologic disorder in women of reproductive age. Approximately 5-10% of reproductive age women have PCOS. This syndrome can have many symptoms. However, the two key components defining this disorder must include chronic anovulation (inability to ovulate an egg) and clinical hyperandrogenism (elevated male type hormones).

The various symptoms of PCOS can be irregular or absent menstrual cycles, infrequent or absent ovulation, excess facial and body hair, male pattern balding, acne of face/back/chest, and infertility. Other findings can include an elevated FSH to LH hormone ratio, elevated levels of male hormones, multiple small cysts of the ovaries and elevated cholesterol.

Some women with PCOS also suffer from other subtle endocrine abnormalities. One is insulin resistance, which affects sugar and fat metabolism, and may increase the long-term risks of heart disease, diabetes and high cholesterol. Insulin resistance (IR), the precursor state to diabetes, is present in 35-40% of women with PCOS, even if they are not overweight. Insulin resistance is diagnosed by blood testing, either as fasting glucose to insulin ratio, or as a complete glucose tolerance test (GTT). Long term follow up of women with PCOS reveals that up to 40% develop impaired glucose processing or diabetes by age 40. The prevalence of diabetes in women with PCOS is seven times higher than for the non-PCOS population. Excessive insulin production is thought to promote excess male hormone production, though the actual mechanism explaining this observation is still unclear.

The causes of PCOS are unknown. We do know that the imbalance of the ovarian hormones exists, which prevents the eggs from growing and ovulating every month. Additionally, this imbalance contributes to an excess of male hormone production by the ovaries, which can be worsened by insulin resistance. There is no cure for PCOS, though the various symptoms can be addressed and managed, and therefore help reduce the risk of long-term health consequences.

Numerous strategies are available for women with PCOS wishing to achieve pregnancy.

For overweight women, simply loosing 10-15% of total weight may be enough to allow spontaneous ovulation to occur. If so, then fertility medications would not be needed.

If fertility medications are required, the first and simplest step is to use the fertility pill Clomid (Clomiphene Citrate). We typically start treatment with the lowest dose (50 mg/day), and once a dose which achieves ovulation is determined, we remain on this dose for future cycles.

If ovulation is not achieved using a dose of 200 mg/day, then other strategies have to be investigated. These strategies include using injectable medications (gonadotropins), which are administered using a "low-slow" protocol. When using injectable medications we must be careful to use enough mediation to have one or two eggs grow, but not so much medication that too many eggs grow. This strategy of using low doses of medications, with slow increments in dosage increase, describe the "low-slow" protocol.

If this strategy proves ineffective, then pursuing in vitro fertilization (IVF) is the next treatment option.

In 1935, Stein and Leventhal originally described the syndrome we now call PCOS. Their strategy for treatment was to surgically reduce the size of the ovaries by performing a "wedge resection" (removing a wedge of ovarian tissue). This procedure would result in a decrease in male hormone production by the ovaries, and would allow approximately 80% of the patients to ovulate. Today, we can surgically perform a similar operation called "ovarian cautery or drilling", which is performed by laparoscopy. This procedure is a treatment option for women who fail medications (Clomid or gonadotropins), and who may not want to pursue other available options. Ovarian cautery provides approximately an 80% chance of spontaneous ovulation. Patients who are not spontaneously ovulatory may be more Clomid "sensitive". Therefore, resuming Clomid therapy may now provide ovulatory cycles.

For patients diagnosed with insulin resistance, there is another treatment strategy. Insulin-sensitizing medications can be used to decrease insulin levels, which may help restore the normal ovarian hormone profile (i.e. reduce male hormone), thus allowing for spontaneous ovulation to occur in about 75% of patients. The most commonly used medication is Metformin (Glucophage). There are newer insulin-sensitizing medications available, though these have not been studied extensively in PCOS patients (rosiglitazone maleate (Avantia), pioglitazone hydrochloride (Actos)). Studies with Metformin indicate that most women with PCOS and IR will spontaneous ovulate after 3 months of treatment, or if not ovulatory, will become Clomid "sensitive". One must be carefully screened prior to a course of Metformin, and must be monitored during treatment. Side effects are mostly gastrointestinal (nausea, vomiting, diarrhea).

As with any endocrinologic disorder, patients need a full and complete workup with a physician experienced in that particular disorder. Your reproductive endocrinologist will review old medical records and may ask you to have additional testing. Once all of this information is available, and once a full infertility evaluation is completed (eg. semen analysis, hysterosalpingogram as needed), then treatment options can be reviewed. When you and your partner have decided on the best initial plan, a fertility specialist can proceed with treatment.
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About the Author

Dr. Herbert is a fertility expert and an innovator in the field.

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