Ovarian Syndrome Is Under-Diagnosed
Polycystic ovarian syndrome, affecting at least 5 million American women, has the rather startling symptoms of excessive facial hair, acne, high male hormone levels, irregular periods, infertility, significant weight gain and a propensity toward diabetes. These factors notwithstanding, it’s believed to be vastly under-diagnosed.It’s only recently that endocrinologists have 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.
The syndrome, once called “diabetes of the bearded woman,” is now viewed as a serious hormonal imbalance triggered in part by faulty genes for sex hormones and other genes involved in a serious condition called insulin resistance, which often leads to diabetes.
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 and can later become standard adult onset diabetes). Preliminary research also suggests that women with the syndrome have a 50% increased risk of heart disease and stroke as well.
Essentially, PCOS is a “vicious cycle,” though it’s unclear which biochemical glitches come first, says Dr. Stanley Korenmann, an endocrinologist at the UCLA School of Medicine. Once the cycle gets started, the hallmark is insulin resistance, which can also be triggered or exacerbated by obesity and inactivity.
In insulin resistance, the pancreas goes into overdrive to make more and more insulin--a frantic attempt to get enough sugar into cells, notes Dr. Edward Horton, director of clinical research at the Joslin Diabetes Center in Boston.
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, Horton notes. This cluster, dubbed PCOS syndrome, is characterized by some of the well-known risk factors for heart disease: elevated triglycerides (fatty acids), low HDL (“good” cholesterol), high blood pressure, changes in blood clotting patterns and a buildup of fatty plaques in arteries.
And that’s just the beginning. In the ovary, excess insulin messes up the normal process by which an aromatase enzyme converts male hormones such as testosterone 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).
And it gets worse. In this high-insulin, testosterone-excess state, the chemical signaling system between the hypothalamus in the brain and the pituitary gland, which lies just below the brain, goes awry, with the result 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, the syndrome is a leading cause of infertility. But there’s another problem, too. Without ovulation, the uterine lining does not shed every month, which raises the risk of endometrial hyperplasia, a precursor of uterine cancer.
Excess testosterone can also lead to insulin resistance, which leads to even greater excess testosterone production by the ovaries, and the cycle continues on its miserable way.
Given such complexity, perhaps it’s not surprising that many women, among them Kristin Rencher, a former investment banker from Portland, Ore., go from doctor to doctor and suffer through agonizing teenage years, until they eventually try and fail to get pregnant and wind up seeing a reproductive endocrinologist who finally diagnoses PCOS.
“Looking back, someone should have known something was wrong when I was 14,” says Rencher, who now heads the Portland-based Polycystic Ovarian Syndrome Assn.
Rencher got her first period at 13, then had none for years. At 14, she developed severe acne. By 19, she began to get excessive hair on her face and abdomen, even between her breasts. She exercised and dieted but still gained 25 pounds. She did get pregnant, with the help of a fertility drug, but it was only when she began trying to have a second child that she combed the Web, diagnosed herself with PCOS and went to a reproductive endocrinologist, who confirmed her diagnosis.
Kim Maynard, 41, a Cohasset, Mass., woman who works as an operations coordinator for a tour company, has an equally horrifying story: Irregular periods, 100 pounds of excess weight, multiple miscarriages (though she has had three children), excessive hair (even on her feet), and now, worst of all, a strong suspicion that her 16-year-old daughter, Amanda, is also developing PCOS.
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, though so far, the drugs must be used “off label” because none has been approved specifically for polycystic ovarian syndrome.
The most important is the class of drugs called insulin sensitizers, says Dr. Andrea Dunaif, a leading PCOS researcher and chief of endocrinology at Northwestern University Medical School in Chicago. This class includes 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 says. Glucophage may also boost the effectiveness of ovulation-stimulating drugs such as Clomid. Dr. Sandra Carson, a reproductive endocrinologist at the Baylor College of Medicine in Houston, agrees. “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, says Dr. Veronica Ravnikar, director of reproductive endocrinology at the University of Massachusetts Medical Center in Worcester. There’s some evidence that doing so may decrease the risk of miscarriage, but many reproductive endocrinologists think it’s safer to stop the drug during pregnancy.
To cope with the hirsutism (excessive hair growth) of PCOS, many women use Vaniqa, a topical cream that speeds cell turnover and slows 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.
A new birth control pill called Yasmin also has spironolactone-like effects, which means in theory it could help with excessive hair growth. Other birth control pills also can help control excessive hair growth and acne, though many women with PCOS simply use bleaching, waxing, electrolysis or laser treatments to control excess body hair.
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 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,” says Maynard. “Get the support you need.”
*
Judy Foreman writes a syndicated column on health issues. She is a fellow in medical ethics at Harvard Medical School. Her column appears occasionally in Health.
