Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 88, Issue 6, Pages 840-847Publisher
WILEY
DOI: 10.1038/clpt.2010.204
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Funding
- NIHR
- Wellcome Trust
- HEFCE
- MRC
- Integrative Mammalian Biology (IMB) Capacity Building Award
- NIHR Biomedical Research Centre
- Medical Research Council [G0701679] Funding Source: researchfish
- National Institute for Health Research [ACF-2008-21-018, CL-2009-21-004] Funding Source: researchfish
- MRC [G0701679] Funding Source: UKRI
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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.
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