Background: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has the potential as a future therapeutic for infertility. Previous studies have observed that kisspeptin increases LH and to a lesser degree FSH when administered to healthy women, which may limit its therapeutic potential. However, studies in women with hypothalamic amenorrhoea show that i.v. infusions of kisspeptin-54 stimulated both LH and FSH equally. Chronic s.c. infusion of kisspeptin via a pump (similar to an insulin pump) may be an ideal route of administration in the future. However, there has been no direct comparison between the routes of administration in humans.
Aim: To compare the effects of i.v. and s.c. administration of kisspeptin-54 on gonadotrophin secretion in healthy females.
Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n=4) received a single 8-h infusion of saline or kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg per h (i.v. and s.c.) in the early follicular phase of consecutive menstrual cycles in random order. Gonadotrophins and oestradiol were measured every 10 min during the infusions.
Results: All doses of kisspeptin-54 administered both i.v. and s.c. increased LH (mean change AUC LH in h/IU per l: −317±731, vehicle; 360±178, i.v. 0.1 nmol/kg per h; 412±446, s.c. 0.1 nmol/kg per h; 4130±1508, i.v. 0.3 nmol/kg per h; 1251±598, s.c. 0.3 nmol/kg per h; 3014±1879, i.v. 1.0 nmol/kg per h; and 2184±474, s.c. 1.0 nmol/kg per h). There was no significant difference between i.v. and s.c. administration on gonadotrophin levels.
Conclusion: We report that i.v. and s.c. administration of kisspeptin-54 at the same dose has no significant difference on gonadotrophin release. This has important implications for the development of kisspeptin to be given subcutaneously at home as a potential future therapeutic for patients with infertility. Further studies are required to establish the optimum dose and duration of treatment.