title: Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54.
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.
  
  
  OBJECTIVE
  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 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 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.
authors: Section of Investigative Medicine (C.N.J., A.A., A.N.C., R.R., A.D.S., G.M.K.N., Z.G.-D., M.A.G., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Department of Imaging (A.M., C.T.), Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London W6 8RF, United Kingdom.
authors: Channa N
authors: CN
authors: Jayasena
authors: Ali
authors: A
authors: Abbara
authors: Johannes D
authors: JD
authors: Veldhuis
authors: Alexander N
authors: AN
authors: Comninos
authors: Risheka
authors: R
authors: Ratnasabapathy
authors: Akila
authors: A
authors: De Silva
authors: Gurjinder M K
authors: GM
authors: Nijher
authors: Zainab
authors: Z
authors: Ganiyu-Dada
authors: Amrish
authors: A
authors: Mehta
authors: Catriona
authors: C
authors: Todd
authors: Mohammad A
authors: MA
authors: Ghatei
authors: Stephen R
authors: SR
authors: Bloom
authors: Waljit S
authors: WS
authors: Dhillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000188:drug therapy* / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007027:Hypothalamic Diseases / Q000188:drug therapy* / Q000378:metabolism*; D007262:Infusions, Intravenous; D059648:Kisspeptins / Q000008:administration & dosage* / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008597:Menstrual Cycle / Q000187:drug effects / Q000378:metabolism; D011673:Pulsatile Flow / Q000187:drug effects; D055815:Young Adult
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone