Increasing LH Pulsatility in Women With Hypothalamic Amenorrhoea Using Intravenous Infusion of Kisspeptin-54

The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 02/2014; 99(6):jc20131569. DOI: 10.1210/jc.2013-1569
Source: PubMed


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 desensitisation. GnRH has paradoxical effects on reproductive activity; we therefore hypothesised that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH / LH pulsatility in women with HA.
Determine whether constant intravenous infusion of kisspeptin 54 temporarily increases pulsatile LH secretion in women with HA.
Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous intravenous infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30 or 1.00nmol/kg/h) was administered. LH pulses were detected using blinded deconvolution.
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<0.01 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 iU/l: 3.92±2.31, vehicle; 23.44±12.59, kisspeptin-54; P<0.05 vs. vehicle).
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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