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A commonly overlooked condition moves to the forefront

When talk turns to critical health issues among women, common issues such as the appropriateness of the recent controversial mammography guidelines get the most attention. However, an often overlooked health issue that is becoming more common among female patients receives little attention in these discussions. Polycystic ovary syndrome (PCOS) is becoming one of the most common female endocrine disorders and affects an estimated 5-10 percent of women between the ages of 12 and 45.

The condition develops when a woman’s ovaries produce excessive amounts of male hormones, typically testosterone, either through the release of excessive luteinizing hormone by the anterior pituitary gland or from hyperinsulinaemia in women whose ovaries are particularly sensitive to this particular syndrome.

One of the nation’s leaders in the study of PCOS is Richard S. Legro, MD, F.A.C.O.G., Department of Obstetrics and Gynecology, Penn State Hershey Medical Center, a recognized expert in the area of reproductive endocrinology. Legro, who completed his medical studies at the Mount Sinai School of Medicine with a residency at the University of Pittsburgh and a fellowship at the University of Southern California, has coauthored two significant PCOS studies in 2010 alone: “Associations of birth weight and gestational age with reproductive and metabolic phenotypes in women with polycystic ovary syndrome and their first-degree relatives” (J Clin Endocrinol Metab 2010 Feb; 95:789–99), and “Family-Based Analysis of Candidate Genes for Polycystic Ovary Syndrome (J Clin Endocrinol Metab 2010 Mar 3; e-pub ahead of print), and is presenting four papers on PCOS projects at this year’s Annual Endocrine Society Meeting in San Diego.

“This is a very common condition and is one of the common causes of infertility among women of child-bearing age,” Legro said, suggesting an affected rate closer to one in every fifteen to twenty-five women. “The nation’s obesity epidemic seemingly has been accompanied by a PCOS epidemic.”

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One of the challenges in dealing with PCOS, researchers suggest, is that it can manifest itself in a wide array of symptoms, each of which may not always be present in all patients, and there has been no distinct common cause identified for the condition.

While some research suggests that insulin resistance can be a significant contributing factor to PCOS, there is still a strong belief that some women may be genetically predisposed to it.  In many instances a mother or sister may present similar symptoms, but no specific genetic link has been positively identified. Clinicians do agree, however, that PCOS is often overlooked and can lead to more serious health complications, as well as psychological problems such as insecurity and depression.

While PCOS can present any number of signs and syndromes, the most common include irregular menstrual periods, elevated levels of androgen, and excessive acne and body hair. Left untreated, however, Legro said that PCOS is commonly believed to lead to more serious conditions such as diabetes, endometrial cancer, infertility, and obesity-related conditions such as high blood pressure. To positively diagnose PCOS, clinicians typically rely on abdominal imaging or laproscopy or a series of blood tests.

While PCOS has received more attention at medical research centers in recent years, Legro maintains there is a lot of work to do, and each new conclusion often creates an entirely new series of questions on the condition, its causes, and its treatments.

“We’re still trying to accurately determine the role of obesity in the development of PCOS,” Legro noted. And while there are a number of accepted treatments for women with PCOS, including lifestyle changes as well as medical and surgical interventions, Legro said the best order of treatment has yet to be fully determined. “There is continued interest in identifying a particular sequence of PCOS-related abnormalities,” he added.

With an eye toward answering many of these lingering questions about PCOS, Legro has taken a leadership role in an array of medical center studies on the condition. These new investigations include examining the effect of the combination therapy of lifestyle changes and metformin on adult and juvenile PCOS patients, the efficacy of Clomiphene Citrate or letrozole on the likelihood of successful pregnancy in women with PCOS, the effect of pretreatment with weight loss or oral contraceptive pill on ovulation and pregnancy rates in women with PCOS, a widespread study to locate the genes for PCOS, and a study to determine if pregnant women with PCOS are more prone to developing gestational diabetes than non-PCOS pregnant women. With technology advancing so quickly, it’s become easy to perform the boy or girl prediction test. He also cited an upcoming study to examine the role of vitamin D on PCOS, including the lack of the vitamin and whether vitamin D supplements are of any consequential benefit in PCOS patients. Other future studies also will try to determine a PCOS patient’s risk for developing diabetes and more detailed family-related studies looking at patients’ dispositions toward PCOS by studying the genetic relationship between patients and their siblings.

Legro is quick to suggest that one of the more common problems in PCOS investigations is that too many researchers don’t stop and question current practice methods, noting that there is now some contrarian thought that weight loss doesn’t have much of an effect on PCOS and PCOS-related conditions. “It is a challenging, two-sided hypothesis,” Legro noted.

Unfortunately, addressing and treating PCOS is not a swift process, and Legro emphasized that the time factor in treating PCOS is most important when it comes to women who are looking to conceive, as even a six- to twelve-month delay can significantly lead to decreased fertility due to aging ovaries.  In obese women seeking fertility, addressing PCOS primarily through weight loss may not be the best option for patients because the brain has come to accept obesity as a normal physical environment and can take time to “reset” to a new lower weight, in the meantime fighting against the weight loss. This delay can often lead to elevated stress levels in patients looking to conceive, further affecting their reproductive capabilities, and rendering the weight loss treatment approach counterintuitive.

Legro says that while more attention is being paid to PCOS, there remains the opportunity for significant “eureka” moments in this area of research. In fact, he acknowledges that his own approach to PCOS and its related research has changed through the years.

“We still haven’t discovered the key mechanism behind the condition or the best treatment,” Legro said. “Of course, we’re still searching for a cure.”

“As I get older, I try to look at things as they are and not as I want them to be,” Legro says.

And while clinicians have taken steps to explore PCOS more fully and raise public awareness of its symptoms and the likelihood of successful treatment, Legro said that researchers and clinicians need to be cognizant of how loud an alarm they sound in spotlighting the condition among patients who may already be hesitant to discuss their health concerns.

“We have to be judicious and guarded in what we say and what we present to the public on PCOS,” Legro says. “We should not unduly raise the overall fear factor among patients without the appropriate data to support our claims.”

– By Cary Boshamer

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