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Home » PCOS Research Points to Gene Defect
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PCOS Research Points to Gene Defect

By medwebOct 29, 2012
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With a five-year renewal of the Northwestern University Specialized Center for Research on Sex Differences, one of 11 National Institutes of Health-supported centers, Andrea Dunaif, MD, professor in medicine, is continuing her push to elevate the world’s understanding of polycystic ovary syndrome.

Men may not have ovaries, but that doesn’t mean they can’t develop some of the features of polycystic ovary syndrome (PCOS). 

That’s one of the reasons Andrea Dunaif, MD, Charles F. Kettering Professor of Endocrinology and Metabolism, would like to change the way scientists think about the complex genetic disease. 

“It should really be seen as a metabolic disorder affecting men as well as women across the lifespan, rather than a female reproductive disorder with metabolic features,” Dunaif said.

The current definition of the disorder is rooted in history. PCOS was first identified in 1935 as a gynecologic condition known as Stein-Leventhal syndrome, named after the physicians who described it.

Since then, the understanding of PCOS has evolved. Symptoms in women often first become apparent in adolescence and may include irregular periods and excess hair on the face, chest, or back – all caused by high levels of male hormones. The syndrome is seen as a major health concern because it is frequently associated with obesity and substantially increases risk for type-2 diabetes and, perhaps, heart disease. It is also among the most common disorders of reproductive-age women, affecting up to 10 percent of the population worldwide.

PCOS runs in families, indicating that there is likely a genetic susceptibility to the disorder. This observation first raised the question as to whether men in PCOS families might also be affected. Dunaif’s research group has been able to show that brothers and fathers of women with PCOS also have elevated male hormone levels and face the same long-term health risks, such as diabetes, obesity, and heart disease. 

“Because this is a genetic condition, our research studying families has provided a powerful resource for finding causal genes,” said Dunaif. “We are very fortunate to have recruited more than 500 families over the years. Many of these families are ideal for the application of the newest technologies for identifying disease genes, such as whole genome sequencing, because we have DNA available from affected and unaffected sisters, as well as both parents.”

Andrea Dunaif, MD, is co-chair of the steering committee for the first NIH-sponsored evidenced-based methodology workshop on PCOS.

Thus far, the research points to the likelihood that the same gene defect is responsible for both the reproductive and the metabolic abnormalities. Sponsored by several National Institutes of Health grants, Dunaif and her co-investigators, Margrit Urbanek, PhD, associate professor of medicine-endocrinology, and M. Geoffrey Hayes, PhD, assistant professor of medicine, are leading an international collaboration to map genes for PCOS. 

 “Ultimately, we hope that we can find what causes the condition so we can develop drugs to reverse or prevent PCOS,” Dunaif said. 

One of the major funding sources for this PCOS research is the Northwestern University Specialized Center for Research (SCOR) on Sex Differences. One of 11 National Institutes of Health-supported centers, the SCOR, directed by Dunaif, is in its 11th year of funding, and was recently awarded renewal for five more years. 

Dunaif is also co-chair of the steering committee for the first NIH-sponsored evidenced-based methodology workshop on PCOS, which will be held in December on the NIH campus. An independent panel with broadly-based expertise will develop a scientific statement based on the information presented at this conference. The consensus statement will advance both clinical care and future research in the field. In addition, Dunaif hopes that this statement will highlight the major health implications of PCOS so that the condition is recognized as an important medical disorder.

“PCOS is a major women’s health problem, and the fact that it is genetic means that the male relatives of affected women are at increased risk for the adverse metabolic outcomes associated with PCOS,” she said.

Dunaif also directs the NIH-supported Building Interdisciplinary Careers in Women’s Health (BIRCWH) program, which focuses on faculty career development. The renewal of the BIRCWH award provides two to four years of support for up to four junior faculty members to conduct interdisciplinary research on sex differences. Twenty-one faculty from five departments at Feinberg and two departments at the Weinberg College of Arts and Sciences are available as mentors.

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