Polycystic Ovarian Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Now researchers are learning that it also has far-reaching effects on a woman's overall health. This hormonal disorder affects about 6 percent of premenopausal women, and its repercussions probably echo throughout life. During the reproductive years, the most common symptom of PCOS is irregular or infrequent menstrual periods. Other signs include prominent facial or body hair, severe acne, thinning hair on the head, and obesity. The disease gets its name from the many small cysts that build up inside the ovaries.

Many therapies target specific symptoms of PCOS, but may not address the underlying cause.

Treatments
Oral contraceptives. Traditionally, physicians have prescribed oral contraceptives (birth control pills) to regulate menstrual periods in women with PCOS. Oral contraceptives contain a combination of hormones (estrogen and progesterone). Used properly, oral contraceptives can assure that women menstruate every four weeks. Because they cause women to menstruate regularly (and, thus, shed the endometrial lining), oral contraceptives as treatment for PCOS help to reduce a woman's risk of endometrial cancer.

Anti-androgens. Anti-androgenic agents, such as spironolactone, block the effect of androgens (male hormones, including testosterone). In high doses, anti-androgens can reduce unwanted hair growth and acne.

Treating infertility. Many assisted-reproduction techniques are available for women who have difficulty conceiving because of PCOS: from oral and injectable medications that stimulate ovulation, to advanced methods of in vitro fertilization including use of donor eggs.

New Treatments
Rather than focusing on relieving specific symptoms, the newer treatments aim at what may be the root cause of PCOS, i.e. insulin resistance. Many of these new therapies are designed to lower insulin levels and, thus, reduce production of testosterone.

• Drug Therapy
  New evidence suggests that using medications that lower insulin levels in the blood may be effective in restoring menstruation and reducing some of the health risks associated with PCOS. Lowering insulin levels also helps to reduce the production of testosterone, thus diminishing many of the symptoms associated with excess testosterone: hair growth on body, alopecia (hair loss on head), acne, obesity and cardiovascular risk.

• Metformin
  Metformin improves both glucose tolerance and insulin sensitivity. It is approved by the FDA as a treatment for diabetes. Metformin is prescribed under the brand name Glucophage made by Bristol-Myers Squibb in 500mg, 850mg and 1000mg tablets. Glucophage is given 2-3 times daily with a meal. If a dose is missed or a meal is skipped take the next dose at the following meal. Do not double the dose at the next meal. Approximately 30 % of patients started on Glucophage will experience gastrointestinal symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence, and loss of appetite). These symptoms are usually temporary (1-4 weeks) and will disappear during continued therapy. It is advisable for new patients to initiate therapy slowly to minimize the gastrointestinal side effects.

• Pioglitazone
  Pioglitazone works primarily by improving insulin sensitivity and glucose tolerance. The FDA approved the drug in July 1999 for use in type 2 diabetes. Pioglitazone is available under the brand name ACTOS, made by Takeda Pharmaceuticals and co-marketed by Eli Lilly. ACTOS is available in 15mg, 30mg, and 45mg tablets. It is taken once daily with or without food. There were few notable side effects in clinical trials. Another added benefit seen with Pioglitazone is the reduction of triglyceride levels. Periodic liver function tests are recommended for the first year of therapy.

• Rosiglitazone
  made by SmithKline Beecham works in a similar fashion to Rezulin® and ACTOS® by improving insulin sensitivity. Avandia is available in 2mg, 4mg and 8mg tablets. Avandia is usually taken twice daily. A low incidence of side effects was noted in clinical trials. Periodic liver function tests are recommended for the first year of therapy.

How safe are these drugs?
All four drugs appear to be relatively safe for use. Fortunately, when given to non-diabetic patients, Glucophage® (metformin), Rezulin® (troglitazone), ACTOS®(pioglitazone) nor Avandia®(rosiglitazone) lowers blood sugar. This eliminates the possibility of hypoglycemia (low blood sugar).

However, Rezulin® can produce a rare side effect leading to elevation of liver enzymes and possible liver damage. Your doctor should check your liver function by blood analysis for the first 8 months of drug therapy to detect any problems early on. Rezulin® should not be prescribed to anyone with pre-existing liver damage.

Glucophage® has been also associated with a rare condition called lactic acidosis. Reported cases have occurred primarily in diabetic patients with severe renal (kidney) insufficiency. Though neither ACTOS® nor Avandia® have been associated with any liver problems, the FDA is requiring monitoring of patients for any signs of liver function abnormalities during the first year of therapy. This is due to the fact that ACTOS®, Avandia® and Rezulin® all belong to the same drug class - thiazolidinedione (TZD's).