POLYCYSTIC OVARIAN SYNDROME
What is PCOS?
Polycystic ovarian syndrome (also referred to as Stein-Leventhal syndrome, polycystic ovarian disease
or hyper androgenic chronic anovulation) is an endocrine disorder found in 5%-10% women. It can
cause a myriad of symptoms that appear, on the surface, to be unrelated, including irregular or absent
Lack of ovulation
Weight gain (particularly around the waist - the "apple" shape as opposed to the "pear" or "hourglass"
shape which is more typical for women)
Hirsutism (excess body hair) which tends to worsen over time
Insulin resistance (now thought to be a cause rather than a symptom, more on this later). When insulin
resistance is found along with high blood pressure, high triclyceride levels, decreased HDL (good
cholesterol) and obesity, it is sometimes termed "Syndrome X".
Multiple small cysts on the ovaries
Acanthosis nigrans (darkening of the skin under the arms and breasts and at the nape of the neck)
What's going on in my body?
In PCOS, a cycle starts wherein the body becomes resistant to insulin, leading to the release of more and more
insulin to compensate. This condition is called hyperinsulinemia. The ovaries of PCOS women seem to be
particularly sensitive to high blood levels of insulin and respond by overproducing androgens (such as
testosterone). This disrupts the "feedback loop" between the ovaries and the pituitary gland, and the pituitary
gland produces too much LH (luteinizing hormone), leading to more overproduction of androgens. The
immature follicles in the ovaries then fail to convert the excess androgens to estrogen, which inhibits the
development of the follicle. Ovulation doesn't take place because the egg couldn't develop properly, and the
immature egg, instead of being released from the ovary, becomes a tiny cyst that starts producing its own supply
of androgens, which interferes with next month's developing follicle. What causes it?
In the past it was thought that PCOS was caused entirely by excess androgen production, but recent research has
shown that the factor that causes the problem is insulin resistance and hyperinsulinemia, which in turn cause
overproduction of androgens. Treatment previously revolved around treating the androgen imbalance, and
wasn't necessarily very effective. Newer treatments focus on the insulin problems and are showing great
promise. There's an excellent diagram of the process at Polycystic Ovary Syndrome: A New Direction in
Treatment. The diagram is about halfway down the page, under the heading "Insulin Resistance in the
Polycystic Ovary Syndrome." The whole article is good and gives a great explanation of the process.
How is it diagnosed?
Doctors often overlook PCOS, though awareness of it is increasing. It is generally diagnosed through various
blood tests and ultrasound. It shouldn't be diagnosed by ultrasound alone, though, because about 20% of women
have polycystic-appearing ovaries - it's a symptom of chronic anovulation, which can be caused by other things.
Blood tests can be done to test a number of different hormone levels - high androgen levels (particularly free
testosterone), high levels of LH or elevated LH to FSH (follicle stimulating hormone) ratio are often the basis
Problems and risks associated with PCOS
Women with PCOS have an increased risk of developing a number of other health conditions. This does not
mean that by having PCOS you are destined to develop any of these problems, just that you have a higher risk
than the general population.
Type II (adult-onset) diabetes. By controlling the production of insulin and with changes in diet, this
risk can be reduced. If it isn't treated, there is up to a 40% risk of developing diabetes by age 40.
High cholesterol and triglyceride levels
Cardiovascular disease. Again, by controlling the production of insulin, this risk can also be greatly
lowered. During treatment cholesterol levels have often been seen to drop down to normal levels as
Endometrial cancer (cancer of the uterine lining). This risk comes from lack of menstruation - if you haven't
reached menopause and aren't having periods on your own on a semi-regular basis, you need to be treated or you
may risk developing endometrial cancer.
Treatment for PCOS
Metformin/Glucophage works primarily by suppressing hepatic glucose production, increasing glucose
utilization in peripheral tissues. It may also reduce intestinal glucose absorption. Since it does not stimulate
production of insulin, it does not cause hypoglycemia if used alone (though hypoglycemia may result if used
with insulin, a sulfonylurea, or with consumption of an excessive amount of alcohol). The kidneys metabolize
The thiazolidinediones (glitazones or TZDs) — troglitazone (Rezulin, which was taken off the market on March
21, 2000), rosiglitazone maleate (Avandia) and pioglitazone hydrochloride (Actos) — work primarily by
improving sensitivity to insulin in muscle and adipose (fat) tissue and also by inhibiting hepatic glucose
production. They are metabolized by the liver and excreted into the bile.
If hypoglycemia is experienced on either type of medication, it is most likely due to insufficient caloric intake,
rather than a direct result of the medication. These medications may also help improve cholesterol and
triglycerides levels, and may restore ovulation in premenopausal women with PCOS or diabetes.
What are the side effects of insulin-sensitizing medications?
Metformin hydrochloride (Glucophage) — Gastrointestinal problems such as diarrhea, nausea, vomiting,
abdominal bloating, flatulence, and anorexia are the most common reactions. Usually the side effects are dose
dependant and diminish over time. Starting with a low dose and building up to the desired maintenance level
may help. The biggest risk, though very rare (1 in 33,000), of metformin is the possibility of lactic acidosis (a
buildup of lactic acid in the blood). Symptoms of lactic acidosis include feeling weak, muscle aches, trouble
breathing, lightheaded or dizziness, or suddenly developing slow or irregular heartbeat.
Rosiglitazone maleate (Avandia) — The most commonly reported side effects include upper respiratory tract
infection, injury, and headache. Use of this medication may contribute to weight gain. Because Avandia is in the
same class of medications as Rezulin, it may reduce effectiveness of oral contraceptives. (Clinical trials
indicated that administration of Rezulin and birth control pills containing ethinyl estradiol and norethindrone
may lower the plasma concentrations of both hormones by approximately 30 percent, which could result in loss
of contraception. Therefore, a higher dose of oral contraceptive or an alternative method should be considered if
pregnancy is not desired.) Avandia is generally considered safer than Rezulin and less likely to cause liver
damage, but it also has not been on the market as long. Liver testing is recommended ever two months the first
year of use, and quarterly thereafter.
Pioglitazone hydrochloride (Actos) — The most commonly reported side effects include upper respiratory tract
infection, headache, sinus infection, muscle soreness, tooth disorder, and sore throat. It may cause mild to
moderate swelling (edema) and decrease in blood count (anemia) in some patients. The prescribing information
indicates that the effect of Actos on oral contraceptives has not been studied, but because of its relation to
Rezulin it is recommended that patients not wishing to become pregnant exercise additional caution regarding
contraception. Like Avandia, Actos is generally considered safer than Rezulin as far as liver toxicity is
concerned, but it is also newer on the market and not used by as many people. Liver testing is recommended
ever two months the first year of use, and quarterly thereafter.
What testing should be done before prescribing insulin-sensitizing medications?
A comprehensive biochemical panel that includes liver enzymes and alanine transaminase (ALT) should be
performed before metformin or one of the thiazolidinediones (Avandia, Actos) are taken. If there are liver or
kidney abnormalities, caution should be used and the benefits weighed before choosing to use these
What is the maximum dosage of metformin?
The maximum recommended dose of metformin is 2550 mg per day (3 x 850 mg pills). The usual dose in
diabetics is 1000 mg twice daily. Studies with metformin for patients with PCOS usually use 500 mg three times
a day or 850 mg twice daily.
What kind of monitoring should be done while on insulin-sensitizing medications, and how often?
Fasting blood sugar, insulin and HbA1c measurements should be performed periodically to monitor glycemic
control and the therapeutic response to medication.
With metformin, it is recommended that kidney function tests be repeated periodically.
For those using Avandia or Actos, ALT levels should be checked every two months for the first year of therapy,
and quarterly thereafter.
Liver function tests should also be obtained if one has symptoms suggestive of hepatic dysfunction, such as
jaundice (yellowing of skin and whites of eyes), nausea, vomiting, abdominal pain, fatigue, anorexia, or dark
Can metformin be used along with one of the glitazones?
Because metformin and glitazones work in different ways to improve insulin utilization, they may have a
synergistic effect when used together. Treatment with more than one medication often increases side effects,
costs, and necessary monitoring, so should only be considered after use of a single medication fails to get the
desired result (lowering of insulin and androgen levels, and restoration of cycles).
How long do the nausea and diarrhea last after starting metformin?
Usually symptoms lessen over time and go away with long-term use (usually after 3-4 weeks at the same dose).
If diarrhea and nausea continue, one should make sure to take the medication in the middle of a meal. Also
consider diet — the uncomfortable side effects may be prolonged by a diet that is high in carbohydrates and/or
high in fat. Reducing both may lessen symptoms.
Is diet modification needed in addition to taking insulin-sensitizing medications?
The medications themselves may help, but lifestyle changes are beneficial. It is generally recommended that
patients taking metformin or one of the glitazones reduce carbohydrate intake and increase exercise to aid in
glucose metabolism and possible weight loss in those who are overweight. Seeking a consult with a registered
dietician and beginning a structured exercise program are central to an effective therapeutic plan.
Is there any benefit to using insulin-sensitizing medications to treat lean PCOS patients or those who do
not test as being insulin resistant?
Some doctors do give insulin-sensitizing medications to patients with PCOS, including lean women, whether or
not they test as clearly being insulin resistant. Though studies are needed to firmly establish the benefit, many
patients appear to experience improvements in symptoms and cycling. The cause of this improvement is unclear.
Is it safe to consume alcoholic beverages while on metformin?
Drinking alcohol while on metformin is not recommended, though not completely banned either. One may feel
the effects of the liquor sooner and become intoxicated more easily. It also increases the risks of hypoglycemia.
Alcohol may work with metformin to increase blood lactate levels, increasing the risk of lactic acidosis.
What is Syndrome X or Metabolic Syndrome?
Syndrome X, also called Metabolic Syndrome or Insulin Resistance Syndrome, is a combination of insulin
resistance or diabetes, dyslipidemia, hypertension, and central obesity.
What is the difference between Syndrome X and PCOS?
One of the biggest differences is that both men and women can have Syndrome X, while men cannot have
PCOS. Syndrome X involves a cluster of symptoms found within the larger scope of PCOS symptoms — it is
this metabolic disorder that contributes most to heart disease.
Is everyone with PCOS also considered to have Syndrome X?
No. To be diagnosed with Syndrome X, one must have insulin resistance, hypertension, obesity and
dyslipidemia. It is possible to have PCOS without having all of these symptoms, and some women with PCOS
may not appear to have any of them.
Web site for more information: www.soulcysters.com