The Infertility Syndrome


Section: special report

Polycystic ovary syndrome is an often ignored disorder that can steal your fertility, ruin your looks, even lead to cancer. Are you one of the 5 million American women who have it? And do you know how to protect yourself?

Ten years ago, Christine Gray was newly wed, rosy-cheeked, and trim enough to wear size 8 suits to her job as a travel agent in Springfield, Ohio. Then Gray's body began to change. Over six months, she put 30 extra pounds onto her 5-foot-5-inch, 140-pound frame.

She became a compulsive dieter, starving herself on very low fat meals, yet the pounds kept coming. "I went for days where I ate a fat-free granola bar for breakfast, lunch, and dinner," she recalls. "But I couldn't lose any weight." By the time she turned 31, the bathroom scale was reading nearly 200. And that wasn't all. Gray began to find dark, coarse hairs sprouting on her upper lip, chin, cheeks, breasts, and belly. She had to pluck, pluck, pluck to hide the unsightly growth; later she began weekly electrolysis.

"I felt more and more unattractive every day," she says. "It was a shock when I would look in the mirror. I'd think, `That's not me.'"

Even worse, Christine and her husband had planned for a squirming brood of kids, but she failed to become pregnant. She visited doctor after doctor and went through costly infertility treatments for five years. Nothing worked.

By mid-1995, feeling moody, depressed, and alone, she turned to the Internet, joining an online support group for people struggling to conceive. There, one night, she read a message from a woman who said she'd finally discovered the cause of her own infertility. It was due to a medical condition, the woman said, and she listed her symptoms. "I looked down the list," Gray remembers, "and went, `I have that, I have that ... oh my gosh.'"

That was when she discovered the name for the private hell she'd been living in. She had an often-ignored but potentially serious disorder called polycystic ovary syndrome, or PCOS.

The syndrome was the reason why she was having no luck getting pregnant: PCOS throws a woman's reproductive hormones out of whack. In fact, it's one of the leading causes of female infertility in the United States.

The hormonal imbalance also accounted for Gray's unwanted hair. Her E-mail correspondents suggested that the syndrome might even explain her weight problems.

There was one thing more the disorder was doing to Gray, although she didn't learn it until later. PCOS was putting her life in jeopardy. Over the past decade it's become clear that the condition, which affects as many as 5 million American women, multiplies the risk of developing cancer, diabetes, and probably even heart disease. Fortunately, doctors have also finally hit upon the first really promising treatments. They include exercise, a diet very different from Gray's low-fat regimen, and, for some women, drugs.

If you have the syndrome, the new approach isn't a guarantee that you'll lose weight, although many women have. But it may provide the best hope yet of fertility. More important, it's the only way to protect your health.

Most people have never heard of polycystic ovary syndrome, but someone they know probably has it. The disorder is surprisingly common, afflicting 5 to 10 percent of women--more than cancers of the breast, ovary, cervix, and uterus .combined.

Exactly why and how it develops remains largely a mystery, though genes seem to play a role. Its name reflects the fact that in women with the syndrome, the ovaries don't look normal: They're covered with small, bubblelike cysts. PCOS was long considered a reproductive problem, plain and simple. But that's changed. As Gray educated herself in a week spent avidly scanning the Internet, one key phrase kept popping up on her computer screen: insulin resistance.

Insulin is the hormone that ushers sugar from the blood to muscle, fat, and liver cells, where it is used as fuel or converted (mostly in the liver) into fatty acids that the body stores as fat. Experts now think a prime culprit in the syndrome is a failure of the cells to accept the sugar deliveries. In an attempt to compensate, the body churns out more insulin, creating a glut that wreaks mayhem throughout a woman's body, starting with the ovaries.

In the childbearing years, a woman's ovaries usually make estrogen and a little bit of testosterone. The pituitary produces hormones, too, which each month direct an egg to ripen within one of the ovaries. The egg then bursts out and heads for the uterus, where a thickened lining is ready for a possible pregnancy. If none takes root, the lining is shed during the menstrual period, and the cycle starts again.

This whole affair requires a finely orchestrated ballet of chemicals in which levels of estrogen, testosterone, and other key hormones leap and fall with perfect timing. In PCOS, however, insulin signals the ovaries and the adrenal glands to crank out extra testosterone, which tromps among the dancers like a bully. The result: Women with the syndrome don't experience the usual hormonal highs and lows, so periods don't take place or come only occasionally.

"Everything just gets frozen," says Richard Legro, a reproductive endocrinologist at the Pennsylvania State University College of Medicine in Hershey. The egg prematurely stops growing, so it never breaks out of the ovary; in other words, ovulation doesn't occur. Over time the ovaries become covered with immature eggs--the cysts. The extra testosterone also can trigger acne, thinning hair, and the growth of mustaches and beards.

Clues to a link between insulin and PCOS date back to 1921, when two French physicians wrote about hirsute ladies who had difficulty metabolizing carbohydrates. They called the condition diabete des femmes a barbe--"diabetes of bearded women." But it wasn't until 1980 that experts on PCOS began to notice their patients often had high insulin readings. Since then, says reproductive endocrinologist Andrea Dunaif of Brigham and Women's Hospital in Boston, studies have detected insulin resistance in woman after woman with the syndrome. At first there appeared to be an easy explanation, as simply being overweight can make you insensitive to insulin. However, many of the women with PCOS in the United States are skinny. To Dunaif and other investigators, it was beginning to look like the syndrome had to be an inherited form of insulin resistance; carrying excess body fat just made it worse.

And that epiphany was alarming. Experts had long known that women with PCOS who go untreated face a substantially greater risk of endometrial cancer: Because the uterine lining may not be shed for long stretches, any premalignant cells are allowed to grow and mm cancerous. But if insulin resistance played a key role, it meant the syndrome posed a far greater threat than anyone ever suspected.

The cells' resistance to insulin makes it hard for them to get the blood sugar they need for fuel, so the pancreas works overtime to make more of the hormone. But studies suggest that in PCOS, the pancreas can't make enough insulin to properly shuttle sugar into cells. Over time, the failure leads to the blood sugar overload of adult diabetes.

Studies in the past few years have begun to show how enormous the risk truly is. In a report released early last year, Dunaif, Legro, and colleagues found that among women with PCOS age 44 or younger, nearly 8 percent had diabetes versus about 1 percent of women of similar age in the general population. Another 31 percent of the PCOS group had a prediabetic condition called glucose intolerance.

Diabetes raises the odds of heart trouble, partly because high insulin levels are implicated in the blood clotting that can lead to a heart attack. The insulin overload also produces elevated levels of bad LDL cholesterol and triglyceride fats, and a shortage of good HDL cholesterol--all classic risk factors for heart attack.

"The syndrome is an overarching women's health disorder," says Dunaif. "It's got it all. In adolescence and young adulthood, it causes these troubling reproductive problems. And then later on, it's a major risk for chronic illness."

At the first hint of bloated cholesterol counts, doctors jump. To ward off a heart attack, they'll ply you with health advice and drugs. And should your blood sugar levels show signs of heading north, that's cause for careful monitoring, testing, and possibly treatment to fend off the insidious creep of diabetes. So it's ironic and maddening that women with PCOS, prime candidates for both of these major chronic diseases, have generally been neglected by the medical profession.

Because it hits every sufferer differently--patients may be fat or thin, with excess hair growth ranging from light to heavy--the disorder often gets missed in the doctor's office. Like Christine Gray, many women struggle with symptoms for years before being diagnosed. Michelle Schaefer, 27, began growing facial hair when she was a teenager. "I really hated the way I looked," says Schaefer, who lives in Joliet, Illinois. "I would pluck five hairs off my chin at night, and there would be five new ones in the morning." And she always had irregular periods. "But every time I went to the doctors, they said it was stress."

Patricia Hicks of Lexington, Kentucky, sought help in 1991 when she was 25 and trying to get pregnant. "I went to the doctor asking, `Why don't I have a period?' He said, `Well, because you're fat, and fat people don't have periods.'" A different OB-GYN eventually figured out she had PCOS. After eight years of fruitless infertility therapies, she and her husband have decided to adopt.

Which points out another concern: Even a diagnosis hasn't always produced help. Typically doctors used a patchwork of therapies that didn't quite cover all the problems. The standard remedy has been the birth control pill because it turns down the ovary's production of sex hormones, slowing hair growth and bringing back regular periods. But the Pill doesn't completely reverse symptoms. Plus, some people can't tolerate the side effects--and it's obviously not a solution for anyone hoping to start a family.

To keep hair growth at bay, patients often need electrolysis, and sometimes even testosterone-blocking medications such as spironolactone, a high blood pressure drug. But it, too, is off-limits for those who want to have children because it can cause birth defects.

The discovery of insulin's role in PCOS, however, has brought hopes for better remedies, ones that may fix the underlying problem and not just reduce but actually eliminate many symptoms. The trick, Legro says, is to pump up the body's sensitivity to insulin and bring levels of the hormone down. "You can do that through diet, weight loss, and exercise," he says. "Or you can do it with drugs."

Perhaps the most striking change in treatment has come with the availability of new kinds of diabetes medications. Previous drugs brought down high blood sugar by boosting insulin levels. But in 1995 came a remedy called metformin (sold as Glucophage) that directly slows the release of sugar into the blood. And in 1997 troglitazone (Rezulin) hit the market, the first in a class of drugs that actually increases the cells' response to insulin.

"I was at times floored by how successfully metformin worked in my PCOS patients," says endocrinologist John Nestler of the Medical College of Virginia in Richmond. "In fact, one of my biggest problems was that women were getting pregnant when they hadn't planned to."

In one of the latest reports, 43 women with PCOS took metformin. None had menstrual cycles. After a few months, however, insulin and testosterone levels dropped, and in almost all cases their periods resumed. All the women were obese when they started the drug, but after a year they'd shed, on average, 25 pounds. Other research suggests that metformin may protect the heart by lowering blood fat levels and high blood pressure. A few studies have found similar benefits from troglitazone for PCOS patients, although it doesn't promote weight loss.

That's not to say the drugs are perfect. Metformin often causes stomach upset, diarrhea, and nausea. And many doctors steer dear of using troglitazone for diabetes because it poses a small risk of liver toxicity that can result in death. Neither medicine has been okayed for PCOS by the Food and Drug Administration, and large trials are still needed to prove its safety for those with the syndrome. Anyone with PCOS wanting to try drug therapy should do so under close watch by an experienced specialist, preferably in a clinical study.

Before any woman pops even one pill, though, experts say she should make some changes in her lifestyle. "The best insulin sensitizers are increased exercise and reduction in weight," says Robert Norman, a reproductive endocrinologist at the University of Adelaide in Australia.

Sedentary women can reap considerable gains in insulin sensitivity after exercising for just a couple of weeks, says Norman. Even walking 20 minutes every day can make a difference. And doctors have always advised overweight women with PCOS to diet, because losing just 5 percent of their weight can restart menstrual cycles and ovulation. Norman has helped many women start families after a six-month program that combines exercise, healthy eating choices, and support-group meetings.

Of course, losing weight and keeping it off is tough for anyone. Christine Gray and many other PCOS sufferers will tell you it's harder--much harder--for them. Since insulin helps the body lay down fat, one theory is that excessive levels of the hormone could make it easier for PCOS women to plump up and harder for them to slim down. "There's good reason to think that might be the case," says Nestler. "But it's controversial."

What is clear is that conventional nutrition advice gets turned on its head for women with PCOS. In the traditional view, fat is bad, and carbohydrates are good. About 50 percent of calories in the average American diet comes from carbohydrates in grains, fruits, and vegetables--and from sugary sodas and snacks like potato chips and pastries. The American Heart Association would like to see an even higher percentage of calories from carbohydrates (healthy, unrefined ones), perhaps 60 percent or more. Fat should be held to 30 percent, the Association says. Heart patients who follow the stricter Dean Ornish approach eat almost no fat and up to 75 percent carbohydrates.

But some PCOS researchers now think it's a mistake for women with the syndrome to take a high-carb approach. During digestion high-carbohydrate foods are broken down particularly quickly in to sugar, provoking an extra-high surge of insulin. For a woman whose insulin levels are already troublingly high, a diet laden with carbohydrates could make symptoms worse.

Very low carb plans, like those in Dr. Atkins' Diet Revolution or Protein Power, have become a passion for women with PCOS. On the Atkins diet, for instance, they avoid potatoes, bread, and most veggies and eat plenty of steak, burger patties, and bacon and eggs, getting no more than about 20 percent of calories from carbohydrates. Many women report that "low carbing" has worked wonders at trimming their waistlines and restoring periods.

Such an approach is no good either, scientists warn. These menus can cause serious health problems for a woman with the syndrome. The Atkins diet provides 60 percent of calories from fat, nearly half of it the artery-clogging, saturated type. That's clearly a bad idea for women already at increased risk of heart disease. For that matter, there's even disagreement about whether low-carb plans offer a weight-loss advantage. Some experts say that whether or not a woman has PCOS, if she loses weight on a low-carb plan, it's because she's simply consuming fewer calories.

What to do? Head for the middle ground. Many patients fare well on a diet that's moderate in both carbs and fat, like that recommended in The Zone, Dunaif says. Its 40-30-30 ratio of carbohydrates to protein to fat makes sense, she says, so long as most of the carbs are in the form of unrefined grains and fiber-rich fruits and vegetables, and the fat is mostly monounsaturated or polyunsaturated. Since fat is more filling than carbs--and won't trigger such a steep insulin spike--Zone fans may have more luck cutting calories because they feel less hungry. "I don't want to plug anyone's book," she says, "but it's a reasonable diet, and it may be particularly useful for these women."

Of course, the Zone's rigid rules won't suit everyone. In the end, women need to find a balanced, moderately low carb way of eating--one they can keep up for the rest of their lives. And that's what Christine Gray has tried to do.

After she found out about PCOS, Gray abandoned her low-fat, high-carb diet. Instead, she stopped counting calories and began her own liberalized version of the Zone.

Gray didn't follow the diet plan to the letter; she just tried to roughly follow the 40-30-30 recipe. At lunch or dinner she would have a lean piece of, say, chicken breast or pork with high-fiber vegetables like broccoli or green beans. She avoided very starchy or sugary foods, including vegetables like potatoes and corn. "Basically," she says, "I just ate whenever I was hungry."

In three months she lost 30 pounds. To further control her insulin, Gray began drug therapy. Now she takes both metformin and troglitazone, although doctors don't usually prescribe the drugs together. Today, Gray is a size 8 again, having trimmed another 40 pounds, and her periods are much more regular. Her desire to have a baby remains unfulfilled; last year her marriage ended in divorce, fractured by the stress of infertility. But in the past few years, she's succeeded in starting a family of a different kind.

After that eye-opening night at her computer in 1995, Gray was angry that none of her doctors had ever suggested her troubles might have been linked to PCOS. She sent an E-mail to 30 online acquaintances who also had the syndrome, suggesting they share information and moral support. Within a few weeks, their circle had blossomed into a formal E-mail list with more than 200 "cysters." And the following year, Gray helped start the Polycystic Ovarian Syndrome Association. Now more than 4,000 people are signed up on six different E-mail lists run by the PCOSA, accessible through its Web site.

Gray estimates there are millions of women out there with undiagnosed PCOS. It's her hope to spare them from the years of loneliness and confusion that she went through. And to judge from its busy online discussion board, the association's Web site is making a real difference.

"It is really great to finally find women like me," wrote one participant. "I thought I was such a freak until I found this site." And in a recent message of gratitude, a woman named Riley said, "My life has gotten better because I have cysters to listen and understand when I thought no one else would."

If you have eight or fewer menstrual periods a year (or did before menopause), odds are high that you have polycystic ovary syndrome. This disorder has long been known to raise the risk of endometrial cancer. Now scientists believe it can bring on diabetes and heart disease, as well. Here's how to find out if you have PCOS--and what to do next.

Check for Symptoms Besides erratic periods, classic signs are excess hair growth on the face, chest, or arms; thinning hair; and acne. All are due to high testosterone, which researchers think is caused by insulin resistance. Obesity and infertility are also common, though not universal among women with the syndrome. If you fit the profile, you should...

Get Tested There's no simple way to diagnose PCOS, and doctors differ in the battery of exams they use. But your blood level of testosterone should be checked. If it's high, your physician must rule out other possible causes, including thyroid disorder, adrenal gland disease, or a tumor of the pituitary gland. That entails blood tests to measure various hormones. (Surprisingly, X-ray or ultrasound exams of the ovaries usually aren't done. That's because as many as 20 percent of healthy women have benign cysts on their ovaries.) If PCOS is confirmed...

Size Up Your Long-Term Risks Your doctor can gauge the health of your uterine lining by taking a careful history of menstrual bleeding or spotting; a biopsy may be in order. You should also have cholesterol and triglyceride fats measured. Your doctor ought to screen you for diabetes using a glucose tolerance test, which checks whether sugar clears from the blood at a normal rate; he or she should conduct the test after an overnight fast and also two hours after a special drink. Your doctor might also test blood insulin levels for signs of insulin resistance. As you make lifestyle changes to lower your heart disease and diabetes risk...

Keep an Eye on Research A compound found in orange peels, called D-chiro-inositol, is the first drug being developed specifically for PCOS. In a small study, it lowered blood levels of insulin, sugar, and testosterone, with no apparent side effects.

The Polycystic Ovarian Syndrome Association offers information about current treatments and upcoming remedies. Call 877/775-7267 to find a local association chapter. Or visit for E-mail lists, discussion boards, and information about studies you can participate in.

This is the second in a 3-part series on the growing concern over insulin resistance. PART ONE (last month) Why it's a hidden risk for heart disease. PART TWO (this month) How it's endangering women's reproductive health. PART THREE (May) What you can do to protect yourself.



By Ingfei Chen

Ingfei Chen is a staff writer.

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