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Early Endocrine, Metabolic, and Sonographic Characteristics of Polycystic Ovary Syndrome (PCOS): Comparison between Nonobese and Obese Adolescents

Department of Pediatrics, Division of Pediatric Endocrinology (M.E.S., M.R.D., A.M.M., L.S.L., S.E.O.), and Department of Obstetrics and Gynecology (R.A.L., R.J., M.F.), Columbia University, College of Physicians and Surgeons, New York, New York 10032

Address all correspondence and requests for reprints to: Sharon E. Oberfield, M.D., Columbia University, College of Physicians and Surgeons, Division of Pediatric Endocrinology, 630 West 168th Street, PH 5 East-522, New York, New York 10032. E-mail: seo8{at}columbia.edu.

Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population.

The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course.

We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 ± 1.9 yr; body mass index (BMI), 22.5 ± 1.5 kg/m²], 22 obese with PCOS (age, 15.5 ± 1.4 yr; BMI, 35.9 ± 6.2 kg/m²), and 15 obese controls (age, 14.4 ± 1.5 yr; BMI, 35.8 ± 7.1 kg/m²). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, 4-androstenedione (4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I_AUC120). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index.

The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, 4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I_AUC120, and log I_AUC120 were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, 4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls.

Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.

This work was supported in part by grants from the National Institutes of Health (RR-00645), Eli Lilly & Co., Pharmacia & Upjohn, Inc., and Genentech, Inc.

Current address for M.E.S.: Jacobi Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461.

Current address for R.J.: Columbia University, Department of Obstetrics/Gynecology, St. Luke’s-Roosevelt Hospital, 1000 10th Avenue, New York, New York 10019.

This work was presented in part at the Annual Meeting of the Lawson Wilkins Pediatric Endocrine Society in Baltimore, MD, May 2002.

Abbreviations: 4-A, 4-Androstenedione; BMI, body mass index; DHEAS, dehydroepiandrosterone sulfate; DHT, dihydrotestosterone; DM, diabetes mellitus; F-G, Ferriman-Gallwey; FGIR, fasting glucose to insulin ratio; G₀, basal glucose level; GCRC, General Clinical Research Center; HDL, high-density lipoprotein; HgbA1c, hemoglobin A1c; I₀, basal insulin level; I_AUC120, insulin area under the curve; IGFBP, IGF-binding protein; ISI(composite), composite insulin sensitivity index; LDL, low-density lipoprotein; OGTT, oral glucose tolerance test; P₀, basal proinsulin level; PA, premature adrenarche; PAO, polycystic- appearing ovaries; PCOS, polycystic ovary syndrome; QUICKI, quantitative insulin sensitivity check index.

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