"General Information About PCOS"
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 periods racerx 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". Acne Male-pattern balding 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 for diagnosis. Problems and risks associated with PCOS 1 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 well. 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 Metformin. 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. 2 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 medications. 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 urine. 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 3 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 4