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- Title
Twice-Weekly Administration of Kisspeptin-54 for 8 Weeks Stimulates Release of Reproductive Hormones in Women With Hypothalamic Amenorrhea.
- Authors
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.
- 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.
- Subjects
INFERTILITY; AMENORRHEA treatment; LUTEINIZING hormone; FOLLICLE-stimulating hormone; KISSPEPTIN neurons; HORMONES
- Publication
Clinical Pharmacology & Therapeutics, 2010, Vol 88, Issue 6, p840
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2010.204