Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea.
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.
Jayasena
C N
CN
Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Nijher
G M K
GM
Abbara
A
A
Murphy
K G
KG
Lim
A
A
Patel
D
D
Mehta
A
A
Todd
C
C
Donaldson
M
M
Trew
G H
GH
Ghatei
M A
MA
Bloom
S R
SR
Dhillo
W S
WS
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
C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone