Kisspeptin-54: Master Regulator of Reproductive Hormone Release
54-residue peptide from the KISS1 gene that drives GnRH release. Investigational for IVF ovulation trigger, hypothalamic amenorrhoea and fertility disorders.
👥 Human studies
- Full name
- Kisspeptin-54 / metastin
- Class
- KISS1R (GPR54) agonist peptide
- Half-life
- ~28 minutes
- Route
- Subcutaneous / IV research
- Developer
- Academic (Dhillo lab, Imperial College London)
- Regulatory status
- Investigational; no approvals
What it is
Kisspeptins are peptides encoded by KISS1, processed into kisspeptin-54 (the longest form) and shorter variants. They signal through KISS1R (GPR54) on hypothalamic GnRH neurons — a gating step essential for puberty initiation and ongoing reproductive function.
How it works
Kisspeptin-54 activates GnRH neurons to release GnRH in a pulsatile fashion, which drives LH and FSH from the pituitary and downstream gonadal hormone production. Endogenous pulses determine the menstrual cycle and spermatogenesis.
Exogenous kisspeptin-54 mimics endogenous pulses, offering a physiologic alternative to hCG-triggered ovulation in IVF and a probe for hypothalamic function in amenorrhoea.
What the research shows
Multiple trials from the Dhillo group explore kisspeptin-54 in IVF ovulation triggering and hypothalamic amenorrhoea.
Abbara A. et al. (2017) — kisspeptin-54 IVF ovulation trigger
Abbara A. et al., J Clin Endocrinol Metab 2017;102:3264–3273. 👥 Human studies
60 women undergoing IVF received kisspeptin-54 in place of hCG trigger.
Good oocyte yield and pregnancy rates with markedly lower risk of ovarian hyperstimulation syndrome (OHSS) than hCG.
Limitations: Single-centre; moderate size; regulatory path still uncertain.
Jayasena CN et al. (2014) — hypothalamic amenorrhoea
Jayasena C.N. et al., J Clin Invest 2014;124:3667–3677. 👥 Human studies
Women with hypothalamic amenorrhoea received pulsatile kisspeptin-54.
LH pulsatility was restored in a subset, suggesting therapeutic potential for fertility restoration.
Limitations: Small cohort; heterogeneous response.
Safety and limitations
Human trials report good tolerability: mild injection-site reactions, occasional flushing. OHSS rate is markedly lower than with hCG trigger — a practical advantage for IVF.
Regulatory path and commercial development remain uncertain; no approved product.