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Twice‐Weekly Administration of Kisspeptin‐54 for 8 Weeks Stimulates Release of Reproductive Hormones in Women With Hypothalamic Amenorrhea
Author(s) -
Jayasena C N,
Nijher G M K,
Abbara A,
Murphy K G,
Lim A,
Patel D,
Mehta A,
Todd C,
Donaldson M,
Trew G H,
Ghatei M A,
Bloom S R,
Dhillo W S
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.204
Subject(s) - kisspeptin , amenorrhea , hormone , medicine , endocrinology , physiology , administration (probate law) , biology , pregnancy , political science , law , genetics
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. Clinical Pharmacology & Therapeutics (2010) 88 6, 840–847. doi: 10.1038/clpt.2010.204