Mothers of women with a common endocrine disorder -- polycystic ovary syndrome (PCOS) -- provide evidence that menstrual irregularity and unhealthy metabolic traits associated with PCOS are inherited and persist with age, according to a new study published today in the Proceedings of the National Academy of Sciences (www.pnas.org).

"There have been few studies looking at the long-term consequences of PCOS," said senior author Andrea Dunaif, M.D., President of The Endocrine Society and Chief of Endocrinology, Metabolism and Molecular Medicine of the Feinberg School of Medicine at Northwestern University in Chicago. "The results of our study strongly suggest that metabolic problems will continue as women with PCOS age, putting them at a high risk for cardiovascular disease and type 2 diabetes."

PCOS is a common problem affecting about 7% young adult women. Women with this disorder have irregular menstrual cycles and elevated levels of male hormones, or androgens, which may result in excessive facial hair growth and acne. PCOS is frequently also associated with insulin resistance and the syndrome is a leading cause of type 2 diabetes in adolescent and young adult women. Women with PCOS also have elevations of low-density lipoprotein (LDL, or "bad") cholesterol and a markedly increased prevalence of a condition called metabolic syndrome. Another negative health feature of PCOS is abnormal lipid levels, but the reasons are controversial. Insulin resistance, type 2 diabetes, increased LDL levels and metabolic syndrome all increase risk for cardiovascular disease.

Studies of women with PCOS, by definition, have been limited to women in their reproductive years; therefore, little is known about their health as they age. The long-term health consequences of PCOS are of considerable importance because many of these women have risk factors that confer substantially increased risk for developing cardiovascular disease and other problems. It is well documented that PCOS runs in families. Though limited, past studies of mothers of women with PCOS have shown increased androgen levels, insulin resistance, and glucose intolerance, suggesting that these traits are inherited.

Armed with this information, Dr. Dunaif and colleagues, Susan Sam, M.D. and Richard S. Legro, M.D., of Pennsylvania State University College of Medicine, in Hershey, Pa., wanted to test their hypothesis that abnormal lipid levels are an inherited trait in families of women with PCOS as well as look at the impact of age on reproductive and metabolic characteristics.

They studied 215 non-Hispanic white mothers of women with PCOS and 62 control women of comparable age, weight, and ethnicity, drawn from the National Health and Nutrition Examination Survey III (NHANES III). The study group was limited to non-Hispanic white women because of the potential confounding effects of ethnicity on insulin sensitivity and lipid levels. All participants were asked to complete a questionnaire on their reproductive history, exercise habits, tobacco use, and alcohol intake.

In investigating lipid levels, the researchers found that mothers of women with PCOS had elevated total and LDL cholesterol but triglycerides and high- density lipoprotein (HDL, or "good") cholesterol did not differ between the groups. The mothers had markers of insulin resistance. They also had an increased prevalence of metabolic syndrome compared to nationwide prevalence in normal women of similar age. The strongest predictor of LDL levels in mothers was their daughters' LDL levels. The researchers had previously found that elevated LDL levels are the predominant lipid abnormality in women with PCOS, a finding that was mirrored in the mothers' group.

Thirty-one percent of mothers reported a history of irregular menses. There were no differences in age or body mass index between these mothers and those with a history of regular menses. Mothers with menstrual issues also had higher levels of androgens, glucose, and LDL compared with mothers with a history of regular menses, suggesting, say researchers, that these mothers may have had PCOS. Total testosterone and unbound testosterone levels were higher in mothers with a history of irregular menses than in the controls. The prevalence of hyperandrogenemia was likely underestimated in this study because of a general decline in ovarian function with age, which leads to lower circulating androgen levels.

"Our study shows that menstrual history is an accurate marker for PCOS in both epidemiologic and genetic studies," said Dr. Legro.

Forty-seven percent of mothers had metabolic syndrome compared with 32 percent of the control group. There was a significant increase in the prevalence of metabolic syndrome in obese mothers compared with the general population represented by the women in NHANES III. Moreover, the researchers believe that the prevalence of metabolic syndrome in mothers is underestimated because mothers receiving medications for hypertension, diabetes, or hyperlipidemia were excluded. Overall, these findings suggest that mothers of women with PCOS should be screened for cardiovascular disease risk factors.

This study was supported by grants from the National Institutes of Health National Institute of Child Health and Human Development and Office of Research on Women's Health.

Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Endocrinologists are specially trained doctors who diagnose, treat and conduct basic and clinical research on complex hormonal disorders such as diabetes, thyroid disease, osteoporosis, obesity, hypertension, cholesterol and reproductive disorders. Today, The Endocrine Society's membership consists of over 13,000 scientists, physicians, educators, nurses and students, in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit the Society's web site at www.endo-society.org

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