Markers of PCOS inherited, persist and raise risk for heart disease, diabetes

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"There have been few studies looking at the long-term consequences of PCOS. Results of our study strongly suggest that metabolic problems will continue as women with PCOS age," said senior author Andrea E. Dunaif, M.D., Charles F. Kettering Professor of Endocrinology at Northwestern University Feinberg School of Medicine.

Dunaif is also professor of medicine and chief of endocrinology, metabolism and molecular medicine at Feinberg and president of The Endocrine Society.

PCOS is a common problem affecting about 7 percent 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. Another negative health feature of PCOS is abnormal lipid levels, but the reasons are controversial. Insulin resistance, type 2 diabetes, increased low-density lipoprotein (LDL) levels and metabolic syndrome all increase risk for heart 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.

Dunaif and colleagues Susan Sam, M.D., of Feinberg, and Richard S. Legro, M.D., of Pennsylvania State University College of Medicine, Hershey, tested their hypothesis that abnormal lipid levels are inherited in families of women with PCOS, and assessed the impact of age on reproductive and metabolic characteristics.

The researchers studied 215 non-Hispanic white mothers of women with PCOS and a control group of 62 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) cholesterol levels did not differ between the groups. The mothers had markers of insulin resistance. They also had an increased prevalence of the metabolic syndrome, compared with 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.

Over 30 percent of mothers reported a history of irregular menstrual periods. There were no differences in age or body mass index between these mothers and those with a history of regular menses. Mothers with menstrual problems also had higher levels of androgens, glucose and LDL compared with mothers with a history of regular menses, suggesting 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 controls. Prevalence of elevated androgen levels was likely underestimated in this study because of a general decline in ovarian function with age, which leads to lower circulating androgen levels.

"Menstrual history is an accurate marker for PCOS in both epidemiologic and genetic studies," Legro said.

Almost 50 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 elevated lipid levels were excluded. Overall, these findings suggest that mothers of women with PCOS should be screened for cardiovascular disease risk factors.

Northwestern University