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Context: Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty., Objective: To assess sex differences in effects of obesity on reproductive hormones and their relation to insulin sensitivity and secretion., Design: Cross-sectional study including anthropometrics, serum and urine reproductive hormone concentrations, and intravenous glucose tolerance testing (IVGTT) to assess acute insulin response to glucose (AIRg), and insulin sensitivity (Si)., Setting: Outpatient academic clinical research center., Patients: Girls (52%) and boys (48%) who were normal weight (NW; n = 51, BMI-Z score = -0.11 ± 0.77, age = 11.5 ± 1.7 years) and obese (n = 53, BMI-Z score = 2.22 ± 0.33, age = 10.9 ± 1.5 years), Tanner stage 2 to 3., Results: Boys with obesity had lower total testosterone (P < 0.0001) and higher concentrations of the urinary estradiol metabolite, E1c, (P = 0.046) than boys with NW. Girls with obesity had higher free androgen index (FAI; P = 0.03) than NW girls. Both boys and girls with obesity had lower sex hormone-binding globulin (SHBG; P < 0.0001) than NW. AIRg was inversely related to SHBG in boys (R = 0.6, P < 0.0001) and girls (R = 0.53, P = 0.0001). Si correlated with higher SHBG in boys (R2 = 0.67, P < 0.0001) and girls (R = 0.5, P = 0.0003), higher total testosterone for boys (R = 0.39, P = 0.01), and lower FAI for girls (R = -0.2, P = 0.04)., Conclusion: Youth with obesity have lower SHBG than youth with NW, but obesity has differential effects on reproductive hormones in girls versus boys, which are apparent early in puberty. Ongoing longitudinal studies will evaluate the impact of obesity on reproductive hormones in girls and boys as puberty progresses., (Copyright © 2019 Endocrine Society.)

Background: Polycystic ovarian syndrome (PCOS) includes insulin resistance (IR) and impaired glucose tolerance (IGT) in youth, and a greatly elevated risk of type 2 diabetes in adulthood. Identifying IR is challenging and documenting IGT requires an oral glucose tolerance test (OGTT). Objective: Identify easily applied surrogate measures for IR and IGT in girls with PCOS. Methods: We studied 28 girls with PCOS (body mass index [BMI] percentile 98 (83.99); 15.5 (14.5,16.6) years of age) and 20 with normal menses [BMI percentile (97 (88.99); 15.5 (13.3,16.1) years]. Hyperinsulinemic‐euglycemic clamps (insulin dose of 80 μU/ml/min) to determine glucose infusion rate (GIR) and a 75 g OGTT were performed. Surrogates for IR including fasting insulin, homeostatic model assessment‐insulin resistant (HOMA‐IR), Matsuda index, and estimate of insulin sensitivity (e‐IS) were compared to IGT status and GIR. Spearman correlations were performed between surrogates and GIR or IGT, and receiver operator curve (ROC) analysis to predict GIR below the median or IGT status. Results: GIR was lower in PCOS (12.9 ± 4.6 vs 17.1 ± 5.1 mg/kg fat‐free mass·min; P = 0.01). Within PCOS, HOMA‐IR (r = −0.78, P < 0.0001), e‐IS (r = 0.70, P < 0.001), and Matsuda (r = 0.533, P < 0.001) correlated with GIR. e‐IS provided a good sensitivity (100%) and specificity (71%) to identify IR (e‐IS cutoff: <6.3, ROC‐area under curve = 0.898). Fasting insulin >22 IU/mL had the best sensitivity (88%), specificity (78%), and ROC (0.760) for IGT status. Conclusions: Girls with PCOS have significant IR, and IGT is common. Both e‐IS and fasting insulin are obtainable without an OGTT or clamp and could be used clinically to guide treatment in PCOS. [ABSTRACT FROM AUTHOR]