title: Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea.
abstract: Kisspeptin is a novel therapeutic target for infertility. A single kisspeptin-54 (KP-54) injection acutely stimulates the release of reproductive hormones in women with hypothalamic amenorrhea (HA), a commonly occurring condition characterized by absence of menstruation; however, twice-daily administration of KP-54 results in tachyphylaxis. We determined the time course of desensitization to twice-daily KP-54 injections, compared the effects of twice-daily and twice-weekly administration regimens of KP-54, and studied the effects of long-term twice-weekly administration of KP-54 on the release of reproductive hormones in women with HA. When KP-54 was administered twice daily, responsiveness to luteinizing hormone (LH) diminished gradually, whereas responsiveness to follicle-stimulating hormone (FSH) was nearly abolished by day 2. Twice-weekly KP-54 administration resulted in only partial desensitization, in contrast to the complete tolerance achieved with twice-daily administration. Women with HA who were treated with twice-weekly KP-54 injections had significantly elevated levels of reproductive hormones after 8 weeks as compared with treatment with saline. No adverse effects were observed. This study provides novel pharmacological data on the effects of KP-54 on the release of reproductive hormones in women with HA.
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Jayasena
authors.forename: G M K
authors.initials: GM
authors.lastname: Nijher
authors.forename: A
authors.initials: A
authors.lastname: Abbara
authors.forename: K G
authors.initials: KG
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Lim
authors.forename: D
authors.initials: D
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Mehta
authors.forename: C
authors.initials: C
authors.lastname: Todd
authors.forename: M
authors.initials: M
authors.lastname: Donaldson
authors.forename: G H
authors.initials: GH
authors.lastname: Trew
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism; D010865:Pilot Projects; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone