Sex Differences in Effects of Obesity on Reproductive Hormones and Glucose Metabolism in Puberty: The Health Influences of Puberty Study

Context: Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty or sex differences in these effects. Objective: To assess sex differences in effects of obesity on reproductive hormones and their relationship 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: Fifty-one normal weight (NW, BMI-Z=-0.11 +/- 0.77, age=11.5 +/- 1.7 years) and 53 obese (BMI-Z=2.22 +/- 0.33, age=10.9 +/- 1.5 years) girls (n=54) and boys (n=50), Tanner stage 2-3. Results: Obese boys had lower total testosterone (p<0.0001) and higher concentrations of the urinary estradiol metabolite, E1c, (p=0.046) than NW boys. Obese girls had higher free androgen index (FAI, p=0.03) than NW girls. Both obese boys and girls had lower sex hormone-binding globulin (SHBG, p<0.0001) than NW. AIRg was inversely related to SHBG in boys (R2= 0.36, p<0.0001) and girls (R2=0.29, p=0.0001). Insulin resistance correlated with lower SHBG in boys (R2=0.45, p<0.0001) and girls (R2=0.24, p=0.0003), lower total testosterone for boys (R2=0.15, p=0.01), and higher FAI for girls (R2=0.08, p=0.04). Conclusion: Obese youth have lower SHBG than NW youth, but obesity has differential effects on reproductive hormones in girls vs. 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.