The longer burn — KP-54 (metastin)
Kisspeptin-54: The Longer Isoform in Clinical Studies
Fifty-four residues, a near-half-hour half-life, the isoform that carried the IVF and amenorrhea trials — the longer-burning signal, cited to source.
The short version
Kisspeptin-54 is the long form of the kisspeptin family — fifty-four amino acids, originally called metastin. It does the same job as the short form (switching on the reproductive signal that drives LH and FSH), but it lasts much longer in the blood: around half an hour, against roughly four minutes for the short version. That staying power is why kisspeptin-54 is the form most of the human clinical studies used — including the IVF trials that triggered egg maturation with no severe over-stimulation, and the studies that coaxed lost menstrual cycles back. The same staying power has a catch: given continuously or twice daily, the effect fades within days as the receptor tires (tachyphylaxis). On this page, kisspeptin-54 is set against the shorter kisspeptin-10 so the trade-off — longer burn, but more prone to fading under continuous use — is clear. It is investigational; nothing here is a dose to follow.
What kisspeptin-54 is
Kisspeptin-54 (KP-54) is the fifty-four-residue isoform cleaved from the KISS1 precursor, with a molecular weight of about 5857 Da [8]. It was the first kisspeptin identified, originally named metastin when KISS1 was catalogued as a metastasis-suppressor gene — so 'metastin' and 'kisspeptin-54' name the same molecule. Like the shorter fragment it ends in the Arg-Phe-amide motif KISS1R requires and acts on the same receptor on hypothalamic GnRH neurons. The difference is size and durability: the larger peptide resists the plasma enzymes that quickly dismantle kisspeptin-10, so its signal burns longer.
The pharmacokinetics: a near-half-hour burn
Kisspeptin-54's defining property is duration. Its measured human plasma half-life is 27.6 ± 1.1 minutes — roughly seven times longer than kisspeptin-10's four-minute flare [8]. A mechanistic comparison found KP-54 reaches far higher peak plasma levels and sustains LH release substantially longer than KP-10 at equimolar doses, attributable to its greater resistance to peptidase cleavage, and that KP-54 also more effectively activated central GnRH neurons [11]. That longer burn is the reason the clinical trials leaned on this isoform: when the goal is a sustained, measurable gonadotropin response over an hour or more, the longer-lived peptide carries it.
Kisspeptin-54 in the clinic: IVF triggering and restored cycles
Kisspeptin-54 carried the headline clinical work. In a Phase 2 randomized trial of 60 women at high risk of OHSS, a subcutaneous kisspeptin-54 bolus (3.2–12.8 nmol/kg) triggered oocyte maturation in 95% of women with no case of moderate, severe or critical OHSS, and the highest live-birth rate (62%) followed the 9.6 nmol/kg dose — supporting kisspeptin-54 as a safer alternative trigger [5]. In women with hypothalamic amenorrhea, continuous IV kisspeptin-54 (0.01–1.00 nmol/kg/h) restored pulsatile LH secretion, lifting LH pulses about threefold and pulse secretory mass about sixfold versus vehicle, though the highest dose produced tachyphylaxis [4]. And the 2025 intranasal study delivered kisspeptin-54 by nasal spray (12.8 nmol/kg), stimulating LH across healthy men, healthy women and amenorrhea without adverse events — proof the long isoform can work without a needle [6]. The recurring caveat is the same one its durability creates: chronic or high-dose kisspeptin-54 desensitizes the axis, so the schedule matters as much as the dose [10].