Insulin Resistance, Hyperinsulinemia, and LH: Relative Roles in Peripubertal Obesity-Associated Hyperandrogenemia.

Context: Peripubertal obesity is associated with variable hyperandrogenemia, but precise mechanisms remain unclear. Objective: To assess insulin resistance, hyperinsulinemia, and LH roles in peripubertal obesity-associated hyperandrogenemia. Design: Cross-sectional analysis. Setting: Academic clinical research unit. Participants: Eleven obese (body mass index for age ≥95%) peripubertal girls. Intervention: Blood samples were taken during a mixed-meal tolerance test (1900 to 2100), overnight (2100 to 0700), while fasting (0700 to 0900), and during an 80 mU/m2/min hyperinsulinemic-euglycemic clamp (0900 to 1100). Main Outcome Measures: The dependent variable was morning free testosterone level; independent variables were insulin sensitivity index (ISI), estimated 24-hour insulin, and estimated 24-hour LH levels. Results: All participants demonstrated insulin resistance and hyperinsulinemia. ISI, but not estimated 24-hour insulin level, correlated positively with morning free testosterone level when correcting for estimated 24-hour LH level and Tanner stage (rs = 0.68, P = 0.046). The correlation between estimated 24-hour LH and free testosterone levels approached significance after adjusting for estimated 24-hour insulin level and Tanner stage (rs = 0.63, P = 0.067). Estimated 24-hour insulin level did not correlate with free testosterone level after adjusting for estimated 24-hour LH level and Tanner stage (rs = 0.47, P = 0.20). Conclusion: In insulin-resistant obese girls with hyperinsulinemia, free testosterone levels correlated positively with insulin sensitivity and, likely, circulating LH concentrations but not with circulating insulin levels. In the setting of relatively uniform hyperinsulinemia, variable steroidogenic-cell insulin sensitivity may correlate with metabolic insulin sensitivity and contribute to variable free testosterone concentrations.

Hyperandrogenemia in obese peripubertal girls: correlates and potential etiological determinants.

Obesity in peripubertal girls is associated with hyperandrogenemia (HA), which can represent a forerunner of polycystic ovary syndrome (PCOS). However, not all obese girls demonstrate HA, and determinants of HA in obese girls remain unclear. We hypothesized that insulin and luteinizing hormone (LH) are independent predictors of free testosterone (T) concentration in obese girls. To assess this further, fasting morning blood samples were collected from 92 obese (BMI-for-age percentile ≥95) girls in various stages of puberty. A multivariate regression model was then constructed using free T (dependent variable), LH, insulin, pubertal group (early, mid-, or late puberty), BMI z-score, and age. Free testosterone (T) concentrations were highly variable among obese girls in each pubertal group. The regression model accounted for roughly half of the variability of free T in obese girls (adjusted R(2) = 0.53, P < 0.001). LH was found to have the greatest independent ability to predict free T, followed by insulin, then age and BMI z-score. Pubertal group was not an independent predictor of free T. We conclude that morning LH and fasting insulin are significant predictors of free T in obese girls, even after adjusting for potential confounders (age, pubertal group, adiposity). We suggest that abnormal LH secretion and hyperinsulinemia can promote HA in some peripubertal girls with obesity.