Kisspeptin advances ovulation in healthy women

Alexander Comninos; Channa Jayasena; Monica Nijher; Ali Abbara; Silva Akila De; Johannes Veldhuis; Risheka Ratnasabapathy; Chioma Izzi-Engbeaya; Adrian Lim; Daksha Patel; Mohammad Ghatei; Steve Bloom; Waljit Dhillo

doi:10.1530/endoabs.31.OC1.8

Background: The KISS1 gene, is a critical regulator of normal reproductive function. In humans, KISS1 deletion results in a failure to go through puberty while activating mutations result in central precocious puberty. Administration of kisspeptin induces ovulation in rodents and sheep. However chronic exposure to exogenous kisspeptin-54 leads to profound tachyphylaxis in women with hypothalamic amenorrhoea. It is not known whether exogenous kisspeptin can alter the menstrual cycle in healthy women.

Aim: To determine the effects of acute and chronic kisspeptin administration on the menstrual cycle in healthy women.

Methods: We performed a prospective, single-blinded, one-way crossover study. Five healthy female volunteers received twice-daily s.c. injections of kisspeptin-54 or saline for 7 days during days 7–14 of their menstrual cycle. All subjects underwent serial assessments of basal reproductive hormones, ultrasound parameters, and LH pulsatility, as well assessment of acute sensitivity to GnRH and kisspeptin injection.

Results: Kisspeptin-54 treatment shortened the menstrual cycle (mean length of menstrual cycle in days: saline 28.6±1.4 vs kisspeptin 26.8±3.1, P<0.01), advanced the onset of highest recorded serum LH (mean menstrual day of highest recorded LH: saline 15.2±1.3 vs kisspeptin 13.0±1.9, P<0.05), and advanced the onset of the luteal phase of menstrual cycle (mean menstrual day of progesterone increase: saline 18.0±2.1 vs kisspeptin 15.8±0.9, P<0.05). On menstrual day 15, the largest ovarian follicle had a significantly higher diameter following kisspeptin-54 when compared with saline (mean diameter of largest follicle (mm): saline 10.0±2.2 vs kisspeptin 15.5±1.2, P<0.05). LH pulsatility was maintained during kisspeptin-54 treatment. Sensitivity to exogenous kisspeptin-54 and exogenous GnRH was maintained during twice-daily kisspeptin-54 administration.

Conclusion: We demonstrate for the first time that exogenous kisspeptin-54 advances the menstrual cycle in healthy women. This data has therapeutic implications for the use of kisspeptin in the treatment of women with reproductive disorders.

Declaration of funding

Wellcome/GSK/NIHR Fellowships, Clinical Lectureships, and Starter grants.

SfE Early Career Grant.

MRC Experimental Medicine project grant.

Integrative Mammalian Biology (IMB) Capacity Building Award and the NIHR Biomedical Research Centre Funding Scheme.

Endocrine Abstracts

OC1.8