OR36-3 CONTINUOUS INTRAVENOUS INFUSION OF KISSPEPTIN-54 STIMULATES PULSATILE LH SECRETION IN WOMEN WITH HYPOTHALAMIC AMENORRHEA

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR36-Ovarian & Uterine Function
Basic/Clinical
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:45 AM
Room 104 (Moscone Center)
Ali Abbara*1, Channa Nalin Jayasena2, Risheka Ratnasabapathy1, Alexander N Comninos1, Johannes D Veldhuis3, Gurjinder M Nijher1, Zainab ganiyu-Dada4, Amrish Mehta5, Catriona Todd6, Mohammad A Ghatei7, Stephen R Bloom1 and Waljit Singh Dhillo1
1Imperial College London, London, United Kingdom, 2Imperial College London, Surbiton, Surrey, United Kingdom, 3Mayo Clinic & Grad Sch of Med, Rochester, MN, 4imperial college london, london, United Kingdom, 5Imperial College NHS trust, London, United Kingdom, 6Imperial College NHS Trust, London, United Kingdom, 7Imperial College, London, United Kingdom
Introduction:

Women with hypothalamic amenorrhoea (HA, hypogonadotrophic hypogonadism associated with low body weight) have reduced luteinising hormone (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 is necessary for fertility. Kisspeptin-54 is a recently identified hormone, which potently stimulates gonadotrophin releasing hormone (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 (mean BMI 18.3; off estrogen supplements for >6 months) each attended six study visits. Participants received a continuous intravenous infusion of vehicle (placebo) or kisspeptin-54 (doses 0.01, 0.03, 0.1, 0.3 or 1 nmol/kg/h) for 8h. Blood was sampled at 10min intervals for measurement of LH. Pulse analysis was determined by a blinded deconvolution method with 93% sensitivity and specificity for identifying the presence of LH pulses.

Results:

As expected, LH pulsatility was minimal in all participants with HA 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 0.10nmol/kg/h infusion (mean pulsatile LH in iU/l: 7.0±4.3, vehicle; 37.9±17.7, 0.10nmol/kg/h 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 in participants with HA (number of LH pulses per 8h: 1.6±0.4, vehicle; 5.0±0.5, most effective dose of kisspeptin-54, P<0.01 vs. vehicle). The mean peak number of pulses during kisspeptin-54 was also 3-fold higher when compared with vehicle in participants with HA (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.

Nothing to Disclose: AA, CNJ, RR, ANC, JDV, GMN, ZG, AM, CT, MAG, SRB, WSD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Medical Research Council UK National Institute for Health Research Wellcome Trust