Kisspeptin-54

Full-length kisspeptin (54 amino acids); binds KISS1R on GnRH neurons with higher receptor occupancy and longer duration than KP-10; induces more sustained GnRH/LH pulses

Kisspeptin-54 (Kp-54) is the primary full-length endogenous form of the KISS1-derived peptide family, a hypothalamic neuropeptide that acts as the central regulator of GnRH pulsatility and reproductive hormone signaling. As a KISS1R agonist, kisspeptin-54 directly stimulates GnRH neurons, initiating LH and FSH release from the pituitary and driving downstream gonadal steroidogenesis in both males and females. Published research documents kisspeptin-54 regulation of the reproductive axis across the menstrual cycle and its emerging potential as a treatment for sexual dysfunction, with studies suggesting effects on reproductive hormone output and libido-related pathways. Kisspeptin-54 is an investigational compound; it is not approved by the FDA for any clinical indication and its applications in sexual health and fertility remain under active investigation. Kisspeptin-54 vs kisspeptin-10: length and activity distinctions Kisspeptin-54 (Kp-54) is the full-length 54-amino-acid endogenous KISS1-derived peptide, while kisspeptin-10 (Kp-10) is the C-terminal decapeptide fragment responsible for KISS1R (GPR54) binding activity. Both isoforms activate the same receptor, but Kp-54 has a longer plasma half-life and sustained GnRH-stimulating activity relative to the shorter fragment, making it the preferred form for clinical research contexts where prolonged hormonal response is required. In research settings, Kp-10's lower cost and simpler synthesis has led to its wider use in mechanistic studies, while Kp-54 is preferred in clinical trials involving ovulation induction. Kisspeptin-54 in IVF: A published phase 2 clinical trial (Abbara et al., NEJM 2020) demonstrated that kisspeptin-54 could serve as an ovulation trigger in IVF — replacing the conventional hCG trigger in women at high risk of ovarian hyperstimulation syndrome (OHSS). The kisspeptin-54 trigger produced lower OHSS rates compared to hCG while maintaining acceptable oocyte yields, establishing it as a clinically relevant alternative trigger agent for high-risk patients. This application positions kisspeptin-54 within fertility medicine as a potential hCG substitute rather than just a mechanistic research tool. It remains investigational outside of trial contexts and is not currently approved by the FDA or EMA for ovulation induction.