Decreasing Insulin Sensitivity in Women Induces Alterations in LH Pulsatility

J Clin Endocrinol Metab. 2016 Aug;101(8):3240-9. doi: 10.1210/jc.2016-1727. Epub 2016 Jun 16.

Abstract

Context: Obesity is associated with neuroendocrine reproductive alterations and decreased fertility.

Objective: The objective of the study was to gain insight into the neuroendocrine mechanisms implicated in these alterations.

Design: The effects on pulsatile LH secretion of 28 days of a hypercaloric diet were studied in lean and regularly cycling female volunteers. Approximately 50% extra calories (3 g sucrose/kg body weight per day and 1 g fat/kg body weight per day) were added to their individual daily requirements. Spontaneous and insulin-stimulated LH secretion was recorded on 2 different days, before and at the end of the caloric load.

Results: The hypercaloric diet induced an average weight gain of 2.0 ± 0.3 kg (P < .05), corresponding to a body mass index increase of 0.7 ± 0.1 kg/m(2) (P < .05). A concomitant decrease of 11.6% ± 4.6% in whole-body insulin sensitivity was also observed (δ = -1.6 ± 0.7 mg/kg · min glucose; P < .05). The frequency of spontaneous and insulin-stimulated pulsatile LH secretion was increased by 17.9% ± 9.0% and 26.5% ± 9.0%, respectively (both P < .05). Spontaneous LH peak amplitude was decreased by 26.5% ± 9.0% (δ = -0.7 ± 0.36 U/L; P < .05), a change correlated with insulin sensitivity.

Conclusions: Short-term weight gain in normal female volunteers induces alterations of LH secretion reminiscent to those observed in obesity. A decrease in insulin sensitivity may constitute a mechanistic link between obesity and its associated neuroendocrine dysfunctions.

Trial registration: ClinicalTrials.gov NCT02233283.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Diet, Atherogenic
  • Diet, High-Fat
  • Feeding Behavior / physiology
  • Female
  • Humans
  • Infertility, Female / blood
  • Infertility, Female / etiology
  • Insulin Resistance / physiology*
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / metabolism*
  • Obesity / blood
  • Obesity / complications
  • Young Adult

Substances

  • Luteinizing Hormone

Associated data

  • ClinicalTrials.gov/NCT02233283