No Longer A Mere Nuisance
As Incidence Rises With Obesity, Medical Community Begins to Take PCOS Seriously
By Stacey Colino
Special to The Washington Post
Tuesday, April 20, 2004; Page HE01
In 2000, Alexandra Papp couldn't make sense of what was happening to her body.
Within a four-month period, the Alexandria woman added 35 pounds to her 5-8, 165-pound frame -- without changing her diet or exercise habits. She developed severe acne -- the scarring kind -- and the hair from her head began falling out in handfuls. "The real tip-off that something was wrong came when I started lactating from both breasts during a clinical breast exam," recalled Papp, now 30. She was not pregnant or breast-feeding at the time.
Papp went from one physician to another in search of a diagnosis. "It was so frustrating," she said. "None of the doctors knew what to do with me."
Finally, an endocrinologist ordered a series of blood tests and in March 2002 diagnosed the problem: polycystic ovary syndrome (PCOS), a hormonal and metabolic disorder that affects 5 to 10 percent of women in the United States and is a leading cause of infertility. PCOS is on the rise, perhaps because obesity appears to increase risk for those predisposed to the condition, said Richard S. Legro, professor of obstetrics and gynecology at the Penn State College of Medicine in Hershey, Pa. "One of the controversies is whether this is a genetic disorder or an environmental disease that's been brought to the forefront because of the obesity epidemic," he said. Half of all PCOS patients are obese, according to a March report in the journal Metabolism.
Because the symptoms can be so diffuse, it often takes several years until the illness is diagnosed. The delay can be aggravating for women discomfited by such symptoms as excess facial and body hair, acne, male-pattern hair loss and irregular periods. It's also worrisome because the disorder can lead to serious health consequences such as diabetes, heart disease and endometrial cancer, as well as pregnancy complications and hypertensive disorders.
"It's a vastly under-diagnosed disease," said John Nestler, professor of medicine and chairman of the division of endocrinology and metabolism at Virginia Commonwealth University in Richmond. "Physicians have been a little cavalier [about] the disorder because until recently there weren't good ways to treat it and because we haven't understood the disease that much. Until 15 years ago, it was a big black box."
In recent years, however, PCOS has come to be recognized as both a hormonal disorder -- marked by excess production of male hormones called androgens -- and a metabolic one -- associated with insulin resistance, an inability to efficiently regulate the body's insulin usage and blood sugar levels.
"Whether the reproductive disorder causes the metabolic disorder or vice versa is still under intense investigation," said Andrea Dunaif, chief of endocrinology at both the Feinberg School of Medicine at Northwestern University and Northwestern Memorial Hospital in Chicago. "It may be that one or more genes cause both -- that's a hypothesis that's being investigated."
Just how or why PCOS develops remains a mystery, although genetic factors seem to play a role. The disorder often runs in families, as Papp later discovered it did in hers.The condition, first identified in 1935, derives its name from characteristic changes to the ovaries observed in many affected women. These women have enlarged ovaries, covered with fluid-filled cysts.
But the presence or absence of these cysts can't be used to confirm or rule out a PCOS diagnosis. So even the name perpetuates misunderstandings about the problem.
These days, said Dunaif, "we don't do ultrasounds [to detect the presence of cysts on the ovaries] in the U.S. because women with PCOS can have completely normal ovaries on ultrasounds." Meanwhile, as many as 30 percent of women who don't have the disorder do have cysts on their ovaries. "It's unfortunate the condition has its name," Dunaif said, "because then people focus on the ovaries when this is a much more systemic disorder that has metabolic consequences."
Because there isn't a definitive blood test or imaging test for the condition, PCOS is to some extent a diagnosis of exclusion. Doctors try to rule out various other conditions -- such as an underactive thyroid or adrenal or pituitary problems -- that could account for symptoms. And they look for two primary criteria -- irregular periods and evidence of elevated male hormones. If insulin resistance is suspected, a physician might also order a glucose tolerance test or a fasting blood sugar test and a complete lipid profile.
High amounts of insulin are tied to metabolic syndrome, a clustering of heart disease risk factors such as lipid abnormalities, hypertension and central body fat. And high insulin levels usually make the condition worse: "A critical theory is that insulin stimulates the ovaries to make testosterone," said Katherine Sherif, director of the Center for Polycystic Ovarian Syndrome at Drexel University School of Medicine in Philadelphia.
Meanwhile, elevated levels of androgens tend to exacerbate the insulin resistance and create other problems. "That excess testosterone not only interferes with a woman's periods, but it does bad things to arteries in women," Sherif said. Associated problems include hypertension and a drop in levels of HDL, the good cholesterol. In the reproductive system, menstrual irregularity is more than a nuisance: The infrequent shedding of the lining of the uterus can promote abnormal growth of uterine tissue, increasing the risk for endometrial cancer.
Whether the hormonal or the metabolic aspects of PCOS are more of a problem depends largely on a woman's phase of life, Dunaif said. In young women, the chief complaints focus on cosmetic issues and infertility. As women age, she said, PCOS "becomes a major metabolic problem" -- one that can increase a woman's risks of developing diabetes and heart disease.
A 1999 study in the Journal of Clinical Endocrinology & Metabolism found that among women with PCOS between the ages of 14 and 44, nearly 8 percent had diabetes and 31 percent had impaired glucose tolerance, a prediabetic condition. The latter rate was nearly three times higher than that found among similar non-PCOS women. Other retrospective studies have found that women with PCOS have up to five times the risk of developing diabetes as do women in the general population. And a 2003 Mayo Clinic study identified yet another pathway through which PCOS may increase a woman's risk of heart disease: Researchers found that potentially dangerous buildups of calcium in coronary arteries was much more common among women with PCOS than in other women.
There is no single specialist who treats PCOS. What's more, said Legro, "there isn't a consensus on treatment." Too often, say experts, the focus is on treating symptoms rather than the more dangerous underlying condition.
Symptoms are often treated individually, based on a woman's foremost health concerns -- and on the physician she consults. A dermatologist might prescribe an acne medication or spironolactone (a diuretic that inhibits androgen activity) for male-pattern hair loss or excessive facial hair, said Sherif. A gynecologist might give oral contraceptives to regulate periods. (While the American College of Obstetricians and Gynecologists offers fairly comprehensive treatment guidance to OB/GYNs, the emphasis is on treating specific symptoms.) A fertility specialist might prescribe clomiphene, gonatrotropins or other drugs to improve the odds of conception. An internist or an endocrinologist might offer a diet drug or regimen, or an insulin-sensitizing drug to boost glucose tolerance.
Lifestyle changes -- improving diet, boosting exercise -- may also be advised, either to improve response to drugs (very overweight women often don't do as well on drugs to induce ovulation, experts say) or reduce the need for them. "Losing weight actually seems to reverse fertility problems in a lot of situations," said Matthew Kim, an assistant professor of medicine in the division of endocrinology and metabolism at Johns Hopkins University in Baltimore.
Lahle Henninger, now 43, of Ashburn, believes she can attest to this. As a young woman, she'd always had irregular periods, and when she did menstruate, she would sometimes hemorrhage because the lining of her uterus had grown so much. Over the years, she'd consulted many doctors for her menstrual problems, as well as the weight struggles, acne and excess body hair that plagued her. But none put the pieces together.
By the time she was diagnosed with PCOS in 1987 -- at the age of 27 -- Henninger had developed fertility problems and diabetes. Because she and her then-husband wanted to start a family, Henninger took the fertility drug Clomid off and on for three years. "The doctors had me on the highest doses, and it just didn't work," she recalled. So the couple adopted three children.
Meanwhile, Henninger took oral contraceptives to regulate her menstrual cycle and went on a low-carb diet to lose weight. After shedding 128 pounds in 13 months, she got her blood sugar under control, along with her previously high cholesterol and blood pressure. Then, in 1998, Henninger became pregnant. "There's no doubt the dietary changes were the key factor, because I started having periods before I got pregnant," she said.
Both high-protein, low-carb and high-carb, lower-protein diets have been tested in overweight women with PCOS; a recent study by researchers at Penn State tied both diets to weight loss as well as improved menstrual regularity, lipid profiles and insulin resistance in obese women with PCOS.
On the Run
Physical activity may be even more important than dietary changes, Nestler says, citing research findings that regular exercise can improve the body's ability to regulate insulin. For this reason, physicians generally recommend that their PCOS patients exercise for 30 to 60 minutes a day, five times a week, which also may facilitate weight loss. However a woman slims down, Dunaif said, "a 10 percent decrease in body weight can restore ovulation, [regular] menstrual cycles, and lower male hormone levels."
But because it's often hard for people to shed pounds and because PCOS is often associated with insulin resistance, many physicians prescribe insulin-sensitizing drugs such as metformin or rosiglitazone -- also used to treat diabetes -- fairly early in treatment.
"I don't believe that drugs are absolutely necessary," Sherif said. "If a patient is willing to make a commitment to diet and exercise for three months, I'm willing to go with that. But most people choose to go on medication right away because many of them have tried diet and exercise before. By the time they get to me, they are so frustrated with trying to lose weight."
Research has found "that when women with PCOS are treated with metformin, they begin to menstruate and ovulate more frequently, and their hair growth gets better," Nestler said. "By treating the metabolic problem, the endocrine problem gets better."
This, in turn, may reduce the risks of diabetes and heart disease.
But metformin can't be taken by people who have liver or kidney problems, Nestler said. And the side effects -- such as diarrhea, nausea, vomiting and abdominal cramping -- can be tough to take. These are "the number one reason people stop taking it," Sherif said. In addition, said Legro, there is still little research on the safety of long-term metformin use by PCOS patients. Researchers are continuing to search for a better solution -- which would be welcome news to Papp, who takes several different drugs for PCOS -- metformin for insulin resistance, a thyroid medication, spironolactone to prevent unwanted hair growth, a facial gel for acne and bromocriptine to prevent lactation.
"I will mostly likely be on a cocktail of drugs until one of two things happen -- my hormones change for whatever reason or I reach menopause," she said. Though Papp has lost some weight by altering her diet and exercise habits, she continues to wrestle with extra pounds and fatigue.
"When you don't lose weight and you're constantly tired, it's really frustrating," she said. "Some women blame themselves for PCOS and weight gain because society believes that if you are overweight, you did something to deserve it. My response to this is, 'I am overweight because I have PCOS.' "•
• The Polycystic Ovarian Syndrome Association, a nonprofit group operated by women with PCOS, offers information about treatments and research as well as discussion boards and referrals to support groups. www.pcosupport.org
• The Endocrine Society, a professional group committed to hormone research, offers information about new research and advocacy efforts on behalf of endocrinology issues. www.endo-society.org
, 301-941-0200. The group's public education affiliate -- the Hormone Foundation -- offers a physician referral service by state and area of expertise. www.hormone.org
, 800-HORMONE (800-467-6663).
Stacey Colino is a Washington area freelance writer.