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

Christine M Burt Solorzano1,2, Karen L Knudsen3, Amy D Anderson3

  • 1Division of Endocrinology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.

The Journal of Clinical Endocrinology and Metabolism
|June 14, 2018
PubMed

Insights

Obese girls with insulin resistance and hyperinsulinemia show higher free testosterone linked to insulin sensitivity and LH levels, not just insulin. This suggests steroidogenic cell sensitivity plays a role in hyperandrogenemia.

Area of Science:

  • Endocrinology
  • Pediatric Endocrinology
  • Metabolic Disorders

Background:

  • Peripubertal obesity is frequently linked to hyperandrogenemia, a condition where the body produces excessive androgens.
  • The exact mechanisms driving this association, particularly the roles of insulin resistance and luteinizing hormone (LH), remain incompletely understood.

Purpose of the Study:

  • To investigate the relationship between insulin resistance, hyperinsulinemia, and luteinizing hormone (LH) in the context of hyperandrogenemia among obese peripubertal girls.
  • To determine the specific contribution of insulin sensitivity, circulating insulin, and LH levels to morning free testosterone concentrations in this population.

Main Methods:

  • A cross-sectional analysis was conducted involving eleven obese peripubertal girls (BMI for age ≥95th percentile).
  • Blood samples were collected during a mixed-meal tolerance test, overnight, fasting, and during a hyperinsulinemic-euglycemic clamp.
  • Key variables measured included insulin sensitivity index (ISI), estimated 24-hour insulin and LH levels, and morning free testosterone levels.

Main Results:

  • All participants exhibited insulin resistance and hyperinsulinemia.
  • Insulin sensitivity index (ISI) showed a significant positive correlation with morning free testosterone levels, even after adjusting for LH and Tanner stage (rs = 0.68, P = 0.046).
  • While the correlation between LH and free testosterone approached significance (rs = 0.63, P = 0.067), circulating insulin levels did not correlate with free testosterone after adjustments.

Conclusions:

  • In obese peripubertal girls with insulin resistance and hyperinsulinemia, elevated free testosterone levels are associated with better insulin sensitivity and likely with LH concentrations, but not directly with insulin levels.
  • These findings suggest that variable insulin sensitivity in steroidogenic cells may contribute to the observed variations in free testosterone levels within this cohort.
Abstract

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