Background and objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase pre-ovulation when oestradiol levels are naturally high. Therefore we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin.
Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n=4) received an 8 hour SC infusion of kisspeptin-54 0.1, 0.3 or 1.0nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 minutes during the infusions.

Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0.3 and 1.0nmol/kg/h) positively correlated with baseline oestradiol levels (p<0.001). Further statistical analyses showed that in the 1.0nmol/kg/h group a 100pmol/L rise in baseline oestradiol was associated with a 1.0 IU/L increase in LH.
Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotropin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.