Effect of a GnRH injection on kisspeptin levels in girls with suspected precocious puberty: a randomized-controlled pilot study

J Pediatr Endocrinol Metab. 2025 Jan 24;38(3):288-291. doi: 10.1515/jpem-2024-0606. Print 2025 Mar 26.

Abstract

Objectives: Kisspeptin plays a major role in the onset of puberty by stimulating the gonadotropin-releasing hormone (GnRH) neurons. The aim of this study was to investigate whether GnRH inhibits kisspeptin secretion via a negative feedback mechanism and potential associations between kisspeptin levels and other hormones of importance for pubertal onset.

Methods: Thirteen girls with suspected central precocious puberty underwent a GnRH stimulation test twice in a randomized, placebo-controlled manner. Blood was sampled up to 150 min after an IV injection of either Relefact LHRH® or saline. The levels of kisspeptin, acylated ghrelin, ultrasensitive oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin and glucose were analysed.

Results: Baseline kisspeptin levels ranged from 9.9 to 201.6 pg/mL. Neither area under the curve for kisspeptin levels nor peaks were significantly lower after the GnRH injection compared to placebo. Baseline kisspeptin and glucose levels tended to be associated (rho=0.55, p=0.051) but no other associations were found between kisspeptin and other hormones.

Conclusions: Basal levels of kisspeptin vary widely in young girls. We found no evidence of a negative feedback mechanism of GnRH on kisspeptin in this small pilot study. The suggested association between kisspeptin and glucose levels needs further investigations.

Keywords: gonadotropin-releasing hormone; hypothalamic-pituitary-gonadal axis; kisspeptin; precocious puberty.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers* / blood
  • Blood Glucose
  • Child
  • Female
  • Follicle Stimulating Hormone / blood
  • Follow-Up Studies
  • Ghrelin / blood
  • Gonadotropin-Releasing Hormone* / administration & dosage
  • Humans
  • Kisspeptins* / blood
  • Luteinizing Hormone / blood
  • Pilot Projects
  • Prognosis
  • Puberty, Precocious* / blood
  • Puberty, Precocious* / drug therapy

Substances

  • Kisspeptins
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • KISS1 protein, human
  • Biomarkers
  • Ghrelin
  • Blood Glucose