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Abstract: Adolescent girls with polycystic ovary syndrome (PCOS) have increased levels of factors constituting the metabolic syndrome: centripetal obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and hyperinsulinemia. Given the strong association reported between early, persistent obesity and development of metabolic syndrome 10 years later in girls, we speculated that if adolescent girls without PCOS had obesity measures similar to girls with PCOS, they would exhibit similar metabolic syndrome–cardiovascular disease risk factors. Within this context, we compared 37 adolescent girls with PCOS and 2 samples of normal, regularly cycling adolescent girls (controls) of similar ages, selected from the Cincinnati Clinic of the National Heart, Lung, and Blood Institute Growth and Health Study. The first sample included 157 controls selected using a stratified random sample based on age. As expected, girls with PCOS had higher body mass index (BMI), waist circumference, insulin, systolic blood pressure (SBP) and diastolic blood pressure, triglycerides (TGs), lower HDL-C, and higher low-density lipoprotein cholesterol (LDL-C) and free testosterone (FT) than controls. A second sample consisted of girls matched one to one with girls with PCOS for BMI and age. Comparisons of group differences were not significant for insulin, lipids, or blood pressure; girls with PCOS had a trend toward higher values for waist circumference (median, 92.7 vs 87.5 cm; P = .07) and much higher median FT (4.25 vs 1.42 ng/mL, P = .0001). After matching for BMI and age, by conditional regression analysis, we showed that the groups were not differentiated (P > .15) by insulin, HDL-C, LDL-C, TG, SBP, or diastolic blood pressure, but were differentiated by higher FT (P = .0024) and waist circumference (P = .0024) in PCOS than in controls. Prospective longitudinal analyses of NHGS controls showed that changes in BMI from ages 9 to 10 years to ages 15 to 16 years were positively associated with changes in waist circumference (P < .0001), LDL-C (P = .01), TG (P = .008), and SBP (P = .002). These findings suggest that if adolescent girls achieve adiposity equal to girls with PCOS, they then acquire major components of the metabolic syndrome, and excluding high FT and waist circumference, comparable increased cardiovascular disease risk. [Copyright &y& Elsevier]