ECE2014 Oral Communications Neuroendocrinology & Signalling (5 abstracts)
Constant intravenous infusion of kisspeptin-54 restores LH pulsatility in women with hypothalamic amenorrhoea
Channa Jayasena 1 , Ali Abbara 1 , Alexander Comninos 1 , Johannes Veldhuis 2 , Gurjinder Nihjer 1 , Zainab Ganiyu-Dada 1 , Amrish Mehta 1 , Catriona Todd 1 , Mohammad Ghatei 1 , Stephen Bloom 1 & Waljit Dhillo 1
1Imperial College London, London, UK; 2Mayo Clinic, Rochester, Minnesota, USA.
Background: Women with hypothalamic amenorrhoea (HA) have reduced LH pulsatility causing amenorrhea and infertility. Estrogen supplementation provides symptomatic relief for women with HA, but does not restore the pulsatile pattern of LH secretion which necessary for fertility. Kisspeptin-54 is a recently identified hormone, which potently stimulates GNRH secretion within the hypothalamus. The effect of exogenous kisspeptin-54 administration on LH pulsatility in women with HA is not known.
Methods: A single-blinded, placebo-controlled study was performed. Five participants with HA each attended six study visits. Participants received a continuous intravenous infusion of vehicle or kisspeptin-54 (doses 0.01, 0.03, 0.1, 0.3 or 1 nmol/kg per h) for 8 h. Blood was sampled at 10 min intervals for measurement of LH. Pulse analysis was determined by a blinded deconvolution method.
Results: As expected, LH pulsatility was minimal in HA patients during vehicle administration. As previously observed, kisspeptin-54 increased basal LH secretion dose-dependently. However kisspeptin-54 also increased pulsatile LH secretion, up to 5-fold during 0.10 nmol/kg per h infusion (mean pulsatile LH in IU/l: 7.0±4.3, vehicle; 37.9±17.7, kisspeptin-54; P<0.05 vs vehicle). Peak numbers of LH pulses were observed at different doses of kisspeptin-54 in each participant. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6±0.4, vehicle; 5.0±0.5, most effective dose of kisspeptin-54, P<0.01 vs vehicle). The mean secretory mass during kisspeptin-54 was also threefold higher when compared with vehicle (LH pulse secretory mass in IU/l: 3.92±2.31, vehicle; 23.44±12.59, most effective dose of kisspeptin-54; P<0.05 vs vehicle).
Discussion: This data determines for the first time the therapeutic dose-range of kisspeptin administration associated with stimulation of pulsatile LH secretion in the treatment of infertility in women with HA. This finding has important therapeutic implications for the restoration of fertility in women with HA.
Volume 35
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