Sex Differences in Effects of Obesity on Reproductive Hormones and Glucose Metabolism in Early Puberty

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 (AIR(g)), and insulin sensitivity (S-i). 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. AIR(g) 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 (R-2 = 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.