HMGB1 is increased in adolescents with polycystic ovary syndrome (PCOS) and decreases after treatment with myo-inositol (MYO) in combination with alpha-lipoic acid (ALA)

Gynecol Endocrinol. 2020 Jul;36(7):588-593. doi: 10.1080/09513590.2020.1725967. Epub 2020 Feb 13.

Abstract

PCOS treatment should be based on pathophysiology. High-mobility-group-box-1 (HMGB1) was shown to increase in PCOS patients as a consequence of reduced cystic-fibrosis-transmembrane-conductance-regulator (CFTR) expression in the ovary, and was associated with insulin resistance and inflammation, both features of PCOS. Inositols and ALA derivatives could have positive effects on insulin sensitivity, reduce androgens, and improve ovulation rhythm. The aim of this study was to verify changes in HMGB1, in metabolic and endocrine parameters in adolescents with PCOS compared with controls and after treatment with a combination of MYO + ALA. Twenty-three PCOS adolescents and 21 controls matched for age and BMI were enrolled. In all subjects, metabolic and hormonal parameters were assayed. Homeostatic index (HOMA-IR) and the triglyceride/HDL-cholesterol ratio were calculated. Ovarian volumes were evaluated. Patients were treated with MYO + ALA for 6 months. HMGB1 was measured using a specific ELISA assay. HMGB1 was increased in PCOS compared with controls (19.76 ± 5.99 versus 5.65 ± 1.88 ng/ml; p < .05) and normalized after treatment (2.27 ± 0.36 ng/ml, p < .05). Treatment significantly reduced insulin (24.0 ± 4.11 versus 12.13 ± 2.13 uU/ml), HOMA-IR (3.91 ± 0.41 versus 2.42 ± 0.45), and 17-hydroxyprogesterone (1.20 ± 0.15 versus 0.78 ± 0.11 ng/ml). Cholesterol, luteinizing hormone, 17-β-estradiol, delta 4-androstenedione, and testosterone were unchanged. Circulating HMGB1 was increased in PCOS adolescents, and treatment was effective in normalizing HMGB1.

Keywords: HMGB1; PCOS; alpha-lipoic acid; myo-inositol.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Drug Therapy, Combination
  • Estradiol / blood
  • Female
  • HMGB1 Protein / blood*
  • HMGB1 Protein / drug effects
  • Humans
  • Inositol / administration & dosage*
  • Inositol / pharmacology
  • Luteinizing Hormone / blood
  • Ovarian Reserve / drug effects
  • Ovary / diagnostic imaging
  • Ovary / drug effects
  • Polycystic Ovary Syndrome / blood*
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / drug therapy*
  • Testosterone / blood
  • Thioctic Acid / administration & dosage*
  • Thioctic Acid / pharmacology
  • Treatment Outcome
  • Young Adult

Substances

  • HMGB1 Protein
  • Testosterone
  • Inositol
  • Estradiol
  • Thioctic Acid
  • Luteinizing Hormone