Polycystic Ovary Syndrome (PCOS)

Introduction

Polycystic ovary syndrome (PCOS) is a medical condition in which women can experience irregular or absent menstrual bleeding, increased hair growth, infertility, severe acne, thinning hair on the head, and excessive weight gain. PCOS is also known as the Stein-Leventhal 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 pre-menopausal women, and its repercussions probably echo throughout life. The disease gets its name from the many small cysts that build up inside the ovaries. The many cysts in a polycystic ovary are eggs that matured but, due to abnormal hormone levels, were never released. In a normal ovary, a single egg develops and is released each month.

During a woman's reproductive years, infrequent periods are not a harmless condition. If you are having infrequent periods, or had them when you were younger, talk to your physician about this — PCOS is the culprit 80 to 90 percent of the time.

What PCOS Is and Isn't

Some of the symptoms include:

• PCOS appears to be an inherited condition. If you have or had it, encourage your sisters to be tested, or have yourself tested if you have a sister with the syndrome. The central, probably heritable, biochemical abnormality of polycystic ovary syndrome (PCOS) is hyperinsulinemia. This leads to ovarian overproduction of testosterone and to adrenal overproduction of DHEAS and androstenodione (two androgenic [male] sex hormones).  
• These changes, particularly the increased testosterone, in turn affects the pituitary-ovarian axis, leading to abnormal production of LH and FSH, which stimulate the ovaries. The result of LH and FSH abnormalities is ovarian underproduction of estrogen, along with abnormal production of progesterone, overproduction of testosterone, and amenorrhea and infertility.  

Standard Therapies

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

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.

Newer 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

These medications have been shown to reverse endocrine abnormalities seen with PCOS within two to three months. They can result in decreased hair loss, diminish facial and body hair growth, regulate menstruation, weight loss and normal fertility. Some women will actually begin to ovulate on their own, while others may benefit from the combination of one of the newer drugs with Clomid®. Previously women with PCOS tended not to respond well to ovulation induction with Clomid® alone.

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 (Glucophage®). 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 (ACTOS®). 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 (Avandia®) 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.

Safety

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

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. Therefore it should not be use in the presence of renal failure.

None of the insulin sensitizing drugs has been shown to cause birth defects in animal studies, or in women that have become pregnant while taking the medications. Yet none of them have been studied thoroughly during pregnancy. The most prudent policy would be to discontinue the medication once pregnancy is detected. When more data is available from pregnant women this may change, but until then better to error on the side of caution. You or your doctor should report your pregnancy to the drug manufacturer.

Nonmedical Approaches

Many non-medical approaches can relieve or reduce specific symptoms. These include:

Weight loss. Weight loss helps lower the level of insulin that, in turn, reduces the ovaries' production of testosterone, two of the known hormonal problems in PCOS. Weight loss can help women with PCOS in several ways: it reduces a person's risk of cardiovascular disease and non-insulin dependent (type 2) diabetes, and improves the lipid/cholesterol profile.

However, losing weight can be quite challenging for women with PCOS. These women truly have a metabolic cause for their extra weight. Strict behavior modification program that include careful monitoring of carbohydrate intake are the most successful.

Electrolysis. Electrolysis can eliminate or decrease unwanted hair. During electrolysis, individual hair follicles are destroyed by using an electric current.

Alternative therapies. Some women with PCOS find relief from symptoms through alternative therapies such as herbs, acupuncture, homeopathic remedies and other alternative approaches. Please note that the government does not regulate many herbal therapies, so you must be careful about the source of the herb.

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