Okay, 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 – with drugs, including some usually used for diabetes, that can often reverse or at least control some of the most disturbing symptoms
For years, many gynecologists told young women with irregular periods not to worry, or to simply take birth control pills. And that was partly right – 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 (un-released egg follicles), and the more complex and widespread hormonal disruption.
Today, PCOS is 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.
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 and can later become standard adult onset diabetes). Preliminary research also suggests that women with PCOS have a 50 percent 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 PCOS 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, notes Horton. This cluster, dubbed 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 build-up 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, PCOS 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 37-year former investment banker from Portland, Ore., go from doctor to doctor and suffer through agonizing teenaged years (dating is tricky enough even if you’re not fat, bearded and pockmarked!), 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 Association.
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 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, 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, 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,” says Dunaif. Glucophage may also boost the effectiveness of ovulation-stimulating drugs such as Clomid. (And a new, extended release version of Glucophage may have fewer side effects than the traditional one.)
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, 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 and but is believed to be a promising insulin sensitizer. Other insulin sensitizing drugs are also in the works.
To cope with the hirsutism – 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.
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 can also help control both 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 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,” says Kim Maynard of Cohasset. “Look on the Internet. Get the support you need. There are a lot of books out there now – buy them and read them.”
Judy Foreman’s column appears every other week in Health & Science. Her past columns are available on Boston.com and www.myhealthsense.com. Her email address is foreman@globe.com.
Sidebar:
For more information, call the Polycystic Ovarian Syndrome Association (877-775-PCOS, or 7267) or visit the group’s website,www.pcosupport.org
You might also want to read books on PCOS, including “Living with P.C.O.S.,” by Angela Boss and Evelina Weidman Sterling.