| HEALTH SENSE PCOS puts 5 million women at risk By Judy Foreman, 10/9/2001 OK, it's pop-quiz time: What syndrome affects at least 5 million American women, yet is believed to be vastly under diagnosed despite its rather startling symptoms - excessive facial hair, acne, high male hormone levels, irregular periods, infertility, significant weight gain and a strong tendency to become diabetic? If you answered ''polycystic ovarian syndrome,'' or PCOS, you're among the cognoscenti - and possibly well ahead of your doctors, who often spot pieces of the syndrome but fail to put it all together, much less treat it the new way. Drugs, including some usually used for diabetes, can often reverse or at least control some of the most disturbing symptoms - but only after the syndrome has been identified. For years, many gynecologists told young women with irregular periods not to worry, or simply to take birth-control pills. And that was partly correct; the pills do help regularize cycles. But acne, beards and abdominal hair? Could doctors really have dismissed that as just a cosmetic thing? (Ah, yup.) Dramatic weight gain? Could they have tossed that off as just another female character flaw? (You got it.) Out-of-whack insulin levels? Well, that may be a little more understandable. After all, who would think to refer a woman with missed periods to a diabetes specialist? In truth, PCOS has been recognized, by some doctors, for decades; in fact, it used to be called ''diabetes of the bearded woman.'' But it's only recently that endocrinologists have really pieced together the links between the seemingly obvious gynecological symptoms, such as infertility and ovaries full of tiny cysts (unreleased egg follicles), and the more complex and widespread hormonal disruption. PCOS currently is viewed as a serious hormonal imbalance triggered in part by faulty genes that produce sex hormones as well as other genes that contribute to a serious condition called insulin resistance, a precursor of diabetes. Indeed, women with PCOS have seven times the normal risk of diabetes, as well as a higher risk of gestational diabetes, which starts while a woman is pregnant. Preliminary research also suggests that women with PCOS have a 50 percent increased risk of heart disease and stroke as well. Polycystic ovarian syndrome is a vicious cycle, though it's unclear which biochemical glitches come first, said Dr. Stanley Korenmann, an endocrinologist at the UCLA School of Medicine. Insulin resistance is a hallmark of the syndrome. Insulin is vital to the body's ability to process sugar, ferrying the molecules into cells where they can be put to work. In patients with insulin resistance, this process goes awry, prompting the pancreas to make more insulin to compensate. Even if a person is just insulin resistant and never develops outright diabetes, the insulin resistance itself is linked to a whole metabolic cluster of problems, noted Dr. Edward Horton, director of clinical research at the Joslin Diabetes Center in Boston. This cluster is characterized by some of the well-known risk factors for heart disease. And that's just the beginning. In the ovary, excess insulin messes up the normal process by which male hormones such as testosterone are converted into estrogen. The result for many women with PCOS is unusually high levels of testosterone in the blood. The excess testosterone, in turn, causes women to sprout hair in a male pattern, on the face, chest and abdomen, and to get severe acne, which is driven by breakdown products of testosterone. It gets worse. In this high-insulin, testosterone-excess state, the chemical signaling system between the hypothalamus in the brain and the pituitary gland goes awry, so that the pituitary never signals the ovary to release an egg. This means that ovulation fails, and when that happens, a woman becomes infertile. In fact, PCOS is a leading cause of infertility. But there's another problem. Without ovulation, the uterine lining does not shed every month, which raises the risk of endometrial hyperplasia, a precursor of uterine cancer. The good news is that, thanks to the emerging view that insulin resistance is a core part of the PCOS problem, better treatments are becoming available. So far, doctors must use their discretion to prescribe the drugs because, although legally on the market, none have been approved specifically for PCOS by the US Food and Drug Administration. The most important is the class of drugs called insulin sensitizers, said Dr. Andrea Dunaif, a leading PCOS researcher and chief of endocrinology at Northwestern University Medical School in Chicago. The drugs include Glucophage (metformin), Avandia (rosiglitazone) and Actos (pioglitazone). Several studies, including a pivotal one published several years ago in the New England Journal of Medicine, show that Glucophage can help correct the insulin-resistance problem, lower male hormone levels and, in a substantial percent of women, restore ovulation, Dunaif said. Glucophage also might boost the effectiveness of ovulation-stimulating drugs such as Clomid. Dr. Sandra Carson, a reproductive endocrinologist at the Baylor College of Medicine in Houston, said: ''If you break the cycle by breaking insulin resistance, patients may ovulate. It's been quite successful.'' That raises the question, though, of whether newly pregnant women with PCOS should stay on Glucophage during pregnancy, said, Dr. Veronica Ravnikar, director of reproductive endocrinology at the University of Massachusetts Medical Center in Worcester. There is some evidence that doing so may decrease the risk of miscarriage, but many reproductive endocrinologists, including Ravnikar, think it's safer to stop the drug during pregnancy. And while many women, including Kristin Rencher of Oregon, get dramatic weight loss on Glucophage, many others don't, so insulin-sensitizing drugs should not be considered miracle cures for obesity. Soon, a new drug, not yet on the market, may be marketed specifically for PCOS. Made by INSMED, INS-1 is still in clinical trials, but it is believed to be a promising insulin sensitizer. To cope with the excess hair growth of PCOS, many women take Vaniqa, a topical cream that speeds up cell turnover and slows down growth of hair. Alternatively, drugs such as Aldactone (spironolactone), which block the action of male hormones, may also help, though such drugs can be toxic to a fetus. In addition, a new birth-control pill called Yasmin may also help with excessive hair growth. For those who don't want to take birth-control pills, but are concerned about the risk of uterine cancer because of the lack of menstrual periods, one solution is to take a progesterone drug such as Prometrium every few months to induce a period. ''The bottom line for any woman who thinks she, or her daughter, may have PCOS is to keep searching for a doctor who will listen,'' said Maynard. ''Look on the Internet. Get the support you need. There are a lot of books out there now. Buy them and read them.'' For more information, call the Polycystic Ovarian Syndrome Association at 1-877-775-PCOS, or 7267, or visit the group's Web site at www.pcosupport.org. You might also want to read books on PCOS, including ''Living with PCOS'' by Angela Boss. Judy Foreman's column appears every other week in Health-Science. Her past columns are available on Boston.com and www.myhealthsense.com. Her e-mail address is foreman@globe.com. This story ran on page E1 of the Boston Globe on 10/9/2001. © Copyright 2001 Globe Newspaper Company. |