Abnormal Being

I didn't want to be part of the study when I first read the advertisement in the paper. I was sick of all the doctors examining, testing, screening, only to hear the diagnosis: "We don't know." Maybe I didn't even care anymore and maybe, if I ignored all the questions I asked myself, I could be normal.

But abnormal was exactly what countless physicians, gynecologists, and endocrinologists had scribbled on my medical charts: abnormal menstruation, abnormal hormone levels, abnormal ovaries. And for the first time last year I was offered a "real" diagnosis: Polycystic Ovary Syndrome, or PCOS.

Somehow the name reassured: If doctors could name this disorder, they could cure it.

The more I learned about polycystic ovary syndrome (which is also called Stein-Leventhal Syndrome, or Hyperandrogenic Annovulation) the more I identified with the other women, a shocking 5 to 10 percent of all pre-menopausal females, who have some form of the disease. Women who, like me, clung to their diagnoses, not knowing what it meant besides the list of symptoms: menstrual irregularities, hirsutism (increased body and facial hair), acne, infertility. I knew my symptoms, I wanted to understand the disease. I signed up for Richard Legro's study of women with polycystic ovary syndrome.

I was not the only one with questions. For every one I posed, Legro's staff answered it with ten more I hadn't even considered. Overwhelmed by the idea that no one, not even medical researchers, had dissected this syndrome, I began to see the study as a way to be part of the solution to this medical mystery.

girl in hoodie looking down

Meeting Legro was the first step.

I sat rigidly in the cushioned chair, waiting for him. He slipped into his office, shook my hand, and situated himself behind his desk before I even got a chance to introduce myself. His brisk smile and firm handshake offset his young-looking face and red chili-pepper tie. After glancing at the medical questionnaire I had just completed on the clipboard in front of him, he reclined a bit in his chair and laced his fingers behind his head, as if making ready for the anticipated stream of questions I was about to ask. "You should be in our study," he said, adding a soft, understanding smile.

Legro is accustomed to the questions. An assistant professor of obstetrics and gynecology at Penn State's Milton S. Hershey Medical Center, Legro runs one of the few PCOS research centers in the United States. His work is complemented by that of Richard Spielman at the University of Pennsylvania School of Medicine in Philadelphia. Together, the researchers plan to interview and test 5,000 individuals affected by the disease, including the relatives of women with PCOS, in five years.

So far Legro has 500 participants. "I have never had a problem recruiting women to the study, because they are so frustrated by their condition,"; said Legro, as I nodded in silent response. "I am frustrated by their condition too, because I don't know what causes it. When you don't know what causes something, it is hard to know what to tell someone—and how to treat her."

As in my experience, the uncertainty around this syndrome was its most irritating factor. Though it had an official name, polycystic ovary syndrome is not a concrete diagnosis. "No one can agree on what the definition of PCOS is," Legro said. "You can talk about it to ten different doctors and hear ten different things. It doesn't mean they're wrong, it's just that they are all looking at a different part of the elephant. Some think it's the truck, some think it's the tail, the legs, or the toes, but no one's quite seen the whole animal. The inability to arrive at clear diagnostic criteria and the general neglect of women's health issues are the major reasons why this syndrome is so mysterious."

PCOS is the most common cause of irregular periods. According to Legro, eight percent of all women with six or fewer periods per year have the syndrome. Legro classified this as chronic annovulation (lack of ovulation); women with PCOS can range from completely amenorrheic (no periods at all) to oligomenorrheic (experiencing varying intervals of menstrual bleeding). Most women with PCOS also have ovaries characterized by multiple small "cysts," which form due to the partial development of the egg follicles. Elevated levels of androgens are another indication of PCOS. This hormonal imbalance can create improper development and shedding of the uterine lining, hirsutism, and acne.

But the consistency noted by Legro, and the major focus of his study, is the incidence of glucose intolerance among PCOS women. "We find there is a very high level of glucose intolerance. These women have a hard time absorbing the sugars from their bloodstream into their muscle tissue," Legro said. "This is a direct risk factor and precursor of Type II Diabetes Mellitus. PCOS women are in danger of this type of late onset diabetes and its complications," Legro warned. "We suspect that insulin resistance is at the heart of PCOS and that the elevated androgens is a manifestation of the insulin resistance in the ovary. We are finding that 50 percent of the women's first-degree relatives—their parents or siblings—have a diabetic or pre-diabetic condition, such as glucose intolerance." But unfortunately, like PCOS itself, diagnosing and determining how, or if it's even necessary, to treat insulin resistance is also uncertain: As many as 25 percent of the general population have it. Not all insulin resistant individuals develop diabetes, it is only one risk factor. Yet Legro is focusing on the correlation between the reproductive abnormalities of PCOS and the tendency for women with the disorder to be insulin resistant in hopes of finding a connection and a cure.

Many women with PCOS also tend to be obese. "Obesity is in and of itself a risk factor for diabetes, but the combination of obesity and the syndrome is a double whammy," said Legro. Educating at-risk women about preventive diet and exercise programs to lower their chances of diabetes is an important part of Legro's work. That understanding smile he greeted me with is just one sign of his involvement with the support groups he and his colleagues have created for women with PCOS. "I try to keep my patients as updated as possible on any new insights on the syndrome," Legro commented.

One such insight comes from looking at the disease from an evolutionary standpoint, in an attempt to understand why it has survived to be passed through families. "In women who are obese, when they lose weight, they ovulate," Legro said. "So these are the kind of women who would survive the trip across the frontier, thin down, ovulate, and reproduce, so their gene pool is preserved and promoted in a time of stress." This theory reinforces Legro's hunch that PCOS is a genetic disease. "Clearly it is a familial disease," he stated. "But is it due to shared environment and diet, or is it a truly hereditary disease, due to segments of DNA? I'd says it's the latter. That's what this study is all about, finding the cause. Our goal is to see if this is a genetic disease. There appears to be a pattern of inheritance within the family," he added, "but no one has really done these studies yet in a careful, systematic manner." Legro has already found that about one quarter of the sisters of women with PCOS also have the disease; an additional quarter have regular periods but elevated androgens.

Aside from the increased risk of diabetes and obesity, women with PCOS have a greater risk of developing hypertension and lipid abnormalities, which increase their risk for heart disease. Gynecological cancers are a major concern. In PCOS women, the endometrium, or uterine lining, continues to grow; without regular ovulation, the tissue builds up without being shed regularly. This can lead to uterine or endometrial cancer.

Hearing this made me feel like a ticking time bomb. Wondering why a body that appeared to be so young and healthy could be so full of booby traps, I slumped in my chair and glared at Legro across the expanse of his desk. What was in store for women like me and, more importantly, how, in all this uncertainty, could women with PCOS take some control of the fate of their own bodies?

Legro assured me that I was headed in the right direction.

Most gynecologists, like my own, prescribe birth control pills to regulate their patients' menstrual cycles and generally to lower the androgen level—which helps reduce the severity of hirsutism and acne. "Gynecologists are prescribing this for women with PCOS because we have no better treatment," Legro said. "It will improve menstrual cyclicity and counter hirsutism, but it is certainly not the end of the line for treatment. Insulin sensitivity is not improved, and the woman is not ovulating, so clearly it doesn't work for women who want to become pregnant."

Infertility is an uncomfortable reality that comes with a diagnosis of PCOS. Although polycystic ovary syndrome does not always mean a woman cannot conceive, it does make it more difficult. The average woman ovulates 13 times per year. A woman with PCOS may ovulate only once or twice, so these women don't have as many opportunities to become pregnant. Couples dealing with this unpredictability must conceive when the woman's body dictates. "Many of the patients I see in my reproductive endocrinology practice have PCOS and want to conceive," said Legro. "They are not focused on the long-term effects of the syndrome, they want to be pregnant yesterday." But until successful therapies to treat PCOS, and not just its individual symptoms, are developed, conception will remain difficult. The insulin-regulating drugs that are available are new, and it is too soon to say whether or not they are effective and safe for women with PCOS and their babies. Other methods of inducing ovulation are more common, but still tricky according to Legro. "You're always walking a tightrope between over-response and no response when giving women with PCOS treatments to help them conceive." Multiple births, for instance, are common for PCOS women who become pregnant with the help of fertility drugs.

Faced with the increased risks of diabetes, cardiovascular disease, endometrial cancer, and infertility, I wondered aloud if I would even be able to make it to menopause. Androgen-lowering drugs to improve menstrual cyclicity and hormone balance, fertility treatments to get pregnant, and careful diet and exercise programs to prevent disease—to me all these things seemed like quick fixes to hold my reproductive system together. I hoped participating in the PCOS study would be moving toward a cure, and toward my own peace of mind.

Legro gave that to me.

"I am concerned about you down the road," he began, "but I am tremendously optimistic about what we are finding. And you can also use what knowledge we do have to lower your risk of some of these detrimental long-term effects." Legro reminded me that cardiovascular disease is the number-one killer of men and women alike, and that being aware of my biological disposition for it, as well as for uterine cancer and diabetes, could help me take care of my body and prevent these diseases.

While I'm waiting for a treatment for PCOS, there are still a lot of ways I can cope with the syndrome and possibly improve my general health at the same time. PCOS may actually be a useful early indicator of potentially fatal diseases. "You're finding a condition at the time of menarche, at the very onset of menstruation, that may predict the long-term pathology of some of the largest killers of women," Legro stated. "And you may be able to do something about it."

So that was it. I could do something about it—I could be a part of the solution to all the questions surrounding my diagnosed abnormality. And perhaps for the thousands of other women who have this syndrome, the diagnosis of "We don't know" would change to "We understand."

Richard Legro, M.D., is assistant professor of obstetrics and gynecology in the College of Medicine, Milton S. Hershey Medical Center. The PCOS study is funded by the National Institutes of Health and the Medical Center. For more information, contact Sharon Wood, Study Coordinator, Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, PO Box 851, Hershey PA 17033-0851; 717-531-5154 or 1-800-585-9589. See also www.hmc.psu.edu/obgyn/pcos.htm.

Last Updated May 01, 1998