Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54

Channa N. Jayasena, Ali Abbara, Johannes D. Veldhuis, Alexander N. Comninos, Risheka Ratnasabapathy, Akila De Silva, Gurjinder M.K. Nijher, Zainab Ganiyu-Dada, Amrish Mehta, Catriona Todd, Mohammad A. Ghatei, Stephen R. Bloom, Waljit S. Dhillo

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin- 54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was3-fold higher when compared with vehicle (number ofLHpulses per 8h: 1.6±0.4, vehicle; 5.0± 0.5, kisspeptin-54, P = .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P = .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

Original languageEnglish (US)
Pages (from-to)E953-E961
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number6
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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