Introduction: Kisspeptin-54 is a recently identified hormone, which potently stimulates GnRH secretion within the hypothalamus. Women with hypothalamic amenorrhoea (HA, hypogonadotrophic hypogonadism associated with low body weight) have reduced LH pulsatility causing amenorrhea and infertility. We have previously demonstrated that exogenous administration of kisspeptin-54 acutely stimulates gonadotrophin secretion in women with HA. However, it is not known whether exogenous kisspeptin-54 administration can stimulate LH pulsatility.
Methods: A single-blinded, placebo-controlled study was performed. Six participants with HA due to low body weight or exercise (mean BMI 18.3) each attended six study visits. Blood was sampled at 10 min intervals for measurement of LH. Participants received a continuous intravenous infusion of saline (placebo) or kisspeptin-54 (doses 0.01, 0.03, 0.1 or 0.3 nmol/kg per h) for 8 h. LH pulsatility was determined by modified Santen and Bardin analysis.
Results: As expected, LH pulsatility was virtually absent in all participants with HA during saline administration. Administration of kisspeptin-54 significantly increased mean serum LH and the number of LH pulses in a dose-dependent manner. Maximal effects were observed during 0.3 nmol/kg per h kisspeptin-54 infusion, which induced a 12-fold increase in basal LH secretion, and sixfold increase in number of LH pulses (mean LH in IU/l: 1.1, saline; 12.9, 0.3 nmol/kg per h, P=0.011; mean number of pulses/8 h: 0.67, saline; 4.2, 0.3 nmol/kg per h, P=0.003).
Discussion: We demonstrate for the first time that exogenous kisspeptin-54 temporarily restores LH pulsatility in women with HA, which has important therapeutic implications. Further work will determine if repeated administration of kisspeptin-54 is able to restore fertility in women with deficient endogenous LH pulsatility.