Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 99, Issue 6, Pages E953-E961Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2013-1569
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Funding
- Medical Research Council project grant
- Integrative Mammalian Biology Capacity Building Award
- National Institute for Health Research (NIHR) Biomedical Research Centre Funding Scheme
- NIHR Clinical Lectureship
- Academy of Medical Sciences/Wellcome Starter Grant for Clinical Lecturers
- Society for Endocrinology Early Career Grant
- Wellcome Clinical Research training fellowships
- NIHR Academic Clinical Fellowship
- Wellcome/GSK Clinical Research Fellowship
- NIHR Career Development Fellowship
- MRC [G1000455] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL5-Jayasena] Funding Source: researchfish
- Medical Research Council [G1000455] Funding Source: researchfish
- National Institute for Health Research [ACF-2008-21-018, NF-SI-0507-10337, ACF-2010-21-015, CL-2014-21-003, CDF-2009-02-05, CL-2009-21-004, ACF-2011-21-004, NF-SI-0513-10080] Funding Source: researchfish
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Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8h: 1.6 +/- 0.4, vehicle; 5.0 +/- 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 +/- 2.31, vehicle; 23.44 +/- 12.59, kisspeptin-54; P < .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.
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