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Polycystic
Ovary Syndrome - 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.
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