| Diabetes ForecastJune, 2000 Polycystic Ovary Syndrome [Sister To Type 2] Author/s: John Nestler Lately you've been missing periods, but you're not pregnant. What's going on? Is your diabetes involved? Jane is a 31-year-old woman who recently developed type 2 diabetes. When she went to an endocrinologist to learn more about her condition, she was surprised by some of the doctor's questions. He asked her about her menstrual cycle and whether she had any excess hair growth. As it turns out, Jane had been having only four or five menstrual periods a year since she started menstruating at age 14, and never had been able to become pregnant. And she always did have a problem with a little "moustache." Although the questions and answers seemed to Jane to be irrelevant to her case, her doctor was able to clear things up for her by explaining that he suspected a condition called "polycystic ovary syndrome" (PCOS), and that it might be intimately linked to her diabetes. Jane's doctor prescribed metformin, which was effective in treating her diabetes and bringing her blood glucose back to normal. Jane began to menstruate on a regular monthly basis and noticed a decrease in the amount of facial hair growth. Several months later, while she was in good blood glucose control, she became pregnant. What Is PCOS? PCOS is a condition in which a woman's ova, or eggs, mature in the ovary, but are not released. This failure to ovulate results in a decreased frequency of menstrual periods (usually eight or less per year) and causes cysts to develop in the ovaries. Another feature of PCOS is elevated blood levels of male sex hormones such as testosterone, which can promote excess hair growth and acne. Most women with PCOS are overweight. PCOS is the most common cause of infertility among women in the United States. It affects approximately 6 to 10 percent of women of childbearing age, which translates to between 3.5 and 5 million women. PCOS And Type 2 Type 2 diabetes and PCOS may share a common root: insulin resistance. Insulin resistance is a condition in which the body is unable to use insulin efficiently. It is thought to be the most common cause of type 2 diabetes. Most women with PCOS have insulin resistance, regardless of whether they are underweight, normal weight, or overweight. Women who have PCOS are at risk for type 2 diabetes. Research indicates that 30 to 50 percent of overweight women with PCOS develop either impaired glucose tolerance or type 2 diabetes by the age of 30. Impaired glucose tolerance is a condition in which blood glucose is high, but not high enough to prompt a diagnosis of diabetes. Women with PCOS are also at risk for other disorders, many of which are likely to be related to insulin resistance. Such disorders include high blood pressure, abnormal lipids (high triglycerides and low HDL cholesterol), and heart disease. These are the same disorders that women with type 2 diabetes are at risk for developing. Not all women who have insulin resistance will go on to develop type 2 diabetes, but there is still a price to pay. In a young, nondiabetic woman, the pancreas may compensate for insulin resistance by secreting more insulin. Blood glucose levels remain normal, but the level of insulin in the blood becomes elevated. This condition is called hyperinsulinemia. Hyperinsulinemia appears to play a key role in the development of PCOS. Studies have shown that hyperinsulinemia stimulates the production of male sex hormones by the ovaries. It also decreases production of a protein that binds to sex hormones, so the male sex hormones are more available to tissues such as hair follicles. Studies also suggest that hyperinsulinemia may impede ovulation and contribute to infertility. All things added together, PCOS is not just an infertility disorder or a problem with excess hair growth. Rather, it is a metabolic disorder that can affect several of the body's systems. One could argue that the association of PCOS with type 2 diabetes, high blood pressure, abnormal lipids, and heart disease makes PCOS a major general health issue affecting young women. Treatments for type 2 diabetes and obesity can work for PCOS as well. The first line of attack for all three is diet and exercise. If you are obese and have PCOS, losing weight will improve your insulin sensitivity, and the level of insulin in your blood will go down. Your menstrual periods may become more regular, your fertility may improve, and there will be a decrease in any excess hair growth that you may have. If you cannot lose weight, or if you are not overweight to begin with, drugs that improve insulin sensitivity may help. These drugs include metformin, pioglitazone, and rosiglitazone. Several studies indicate that metformin decreases blood levels of testosterone and increases the frequency of ovulation in both overweight and lean women with PCOS. In clinical practice, I have noted that some women with PCOS who were unable to become pregnant were able to conceive when treated with metformin, after traditional treatments for infertility, like the drag clomiphene, failed. In three studies of women with PCOS, troglitazone, an insulin-sensitizer, has produced similar effects. However, troglitazone was pulled from the market in March after the Food and Drug Administration determined it was linked to 61 deaths. Other new and novel insulin-sensitizing agents are being developed, and several of these are also being tested in women with PCOS. If the results are consistent with what has been reported for metformin and troglitazone, it seems likely that the use of insulin-sensitizing drugs will become standard therapy for many women with PCOS. At this time, however, it should be noted that none of the available insulin-sensitizing drugs are approved for treating PCOS, and their use in doing so is considered "off label." Also, pioglitazone and rosiglitazone may pose some risks to a developing fetus once you are pregnant. The labels on both drugs warn that they should be used only if their benefits outweigh any potential risks to the fetus. Studies of insulin-sensitizing drugs in PCOS suggest that women who have both PCOS and type 2 diabetes might benefit the most from treatment with insulin-sensitizing drugs rather than with insulin or a drug that enhances insulin release. There are no firm data on the number of women with PCOS and type 2 diabetes who experienced more frequent ovulation and renewed fertility when they switched from insulin or a sulfonylurea to metformin. However, this has happened with several of my own patients. It is unknown if women who have PCOS and who take metformin or one of the insulin-sensitizers are more likely to have multiple conceptions. PCOS And You: At present, researchers are not sure how many women with diabetes have PCOS, but it seems likely that PCOS occurs in women with diabetes at least as frequently as it does in the general population, if not more. Some studies suggest that certain ethnic groups such as African Americans or Latinos may be at greater risk for the development of PCOS than the general population. Many women with diabetes have decreased ovulation and menstrual periods and these conditions may be related to a number of factors that have nothing to do with PCOS. Nonetheless, if you have irregular menstrual periods or if you have excess hair growth, you should tell your doctor. Because type 2 diabetes, infertility, excess hair growth, high blood pressure, and abnormal lipids can all be interrelated under the umbrella of insulin resistance, ask your doctor to check your blood pressure and cholesterol as well. In all, PCOS and the infertility it causes are just two symptoms of insulin resistance. Therefore, treating and overcoming insulin resistance may improve your diabetes control; if you've had trouble conceiving, it may help you with that problem as well. John Nestler, MD, is professor and chairman of the Division of Endocrinology and Metabolism at Virginia Commonwealth University's Medical College of Virginia in Richmond.COPYRIGHT 2000 American Diabetes Associationin association with The Gale Group and LookSmart. COPYRIGHT 2001 Gale Group |
| PCOS and Type 2 Diabetes |