Kisspeptin-54

KP-54, metastin, KISS1 54-residue peptide, kisspeptin (full-length)

Sexual health, hormones & signalling

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring 54-amino-acid peptide, the full-length product of the KISS1 gene; shorter fragments (kisspeptin-10, -13, -14) share the same active C-terminal end
Mechanism: Activates the kisspeptin receptor (KISS1R, formerly GPR54) on hypothalamic GnRH neurons, which releases GnRH and therefore LH and FSH from the pituitary
Routes studied: Intravenous infusion and subcutaneous bolus (human research); subcutaneous and intraperitoneal (animal)
Dose range reported: Human studies: IV infusion 4 pmol/kg/min (men, Dhillo 2005) or 1 nmol/kg/h (fMRI studies); SC bolus 0.4 nmol/kg (women) up to 1.6–12.8 nmol/kg as a single IVF trigger. Community reports for KP-54 are sparse; most community use involves kisspeptin-10. No approved dose
Half-life: ~28 minutes in human plasma (Dhillo 2005), markedly longer than kisspeptin-10 (~4 min)
Storage: Lyophilised: refrigerate, protect from light. Reconstituted: refrigerate; community practice is use within ~4 weeks
Regulatory status: Not approved for human use anywhere; investigational. Long-acting analogues (e.g. MVT-602/TAK-448) are in development

Doses are as reported in studies or by the community — never recommendations.

1What it is

Kisspeptin-54 is the full-length form of kisspeptin, a hormone the body makes from the KISS1 gene. It was discovered in 1996 as a tumour-metastasis suppressor (hence the old name "metastin"), and only in 2003 did two groups show that people with inactivating KISS1R mutations fail to go through puberty. That made kisspeptin the master switch sitting above GnRH in the reproductive axis. The 54-residue form circulates in blood and is the form used in nearly all human research, which has been led by a group at Imperial College London since 2005. Kisspeptin-10 (profile #45) is a fragment with the same receptor activity but a much shorter .

Kisspeptin-54 is a naturally occurring hormone, not a synthetic design. The synthetic copy used in research is identical in sequence.

2How it's thought to work

KISS1R activation on GnRH neurons triggers GnRH release into the pituitary portal blood. The pituitary then releases LH (and, to a lesser degree, FSH), which drives testosterone in men and oestradiol/progesterone and ovulation in women.

Because it acts above the pituitary, it only works if the GnRH neurons and pituitary are intact; it does nothing in people with pituitary failure.

Continuous or very frequent exposure desensitises the system (tachyphylaxis), so pulsatile or intermittent dosing matters.

KISS1R is also expressed in limbic brain regions, which is the basis for research on sexual and emotional processing, and in the pancreas, where kisspeptin may modulate insulin release.

Kisspeptin-54 at the KISS1R receptor on GnRH neurons — the same receptor and the same action as the shorter kisspeptin-10, which is why the drawing is shared. It triggers GnRH release and with it LH and FSH, the switch that starts puberty and sustains reproductive function.Schematic — not to scale

3What the research shows

Graded A/B

Stimulation of LH, FSH and sex steroids

IV infusion in healthy men raised LH, FSH and testosterone in a dose-dependent way (Dhillo 2005, JCEM). In women the LH response depends on cycle phase and is largest in the preovulatory phase (Dhillo 2007, JCEM). Responses are robust and reproducible across more than a dozen studies. [1][2]

Graded A/B

Oocyte maturation trigger in IVF

A single SC bolus (1.6–12.8 nmol/kg) matured oocytes in 51 of 53 women undergoing IVF, with 12 live births, without the ovarian hyperstimulation seen with hCG triggers (Jayasena 2014, J Clin Invest). In women at high risk of OHSS, kisspeptin-54 triggering produced no cases of moderate or severe OHSS (Abbara 2015, JCEM), and a second dose improved oocyte yield (Abbara 2017, JCEM). These are phase 2 studies; it is not an approved trigger. [5][6]

Hypothalamic amenorrhoea

Twice-daily SC injections for two weeks initially restored LH pulses but the response faded within days (tachyphylaxis; Jayasena 2009, JCEM). Twice-weekly dosing for eight weeks maintained gonadotrophin responses without desensitisation (Jayasena 2013, Clin Pharmacol Ther). [3][4]

Graded A (small)

Sexual and emotional brain processing

In randomised, placebo-controlled crossover fMRI studies, kisspeptin infusion enhanced limbic activity in response to sexual and bonding images and improved mood scores in healthy men (Comninos 2017, J Clin Invest). In men with hypoactive sexual desire disorder it increased brain activity in sexual-processing regions and penile tumescence (Mills 2023, JAMA Netw Open); a parallel study in women reported similar brain effects (Thurston 2022, JAMA Netw Open). These are mechanistic studies of a few dozen participants each, not treatment trials. [7][8]

Glucose and insulin

IV kisspeptin-54 enhanced glucose-stimulated insulin secretion in healthy men without changing appetite (Izzi-Engbeaya 2018, Diabetes Obes Metab). Small, single-session. [9]

"HPTA restart" after anabolic steroid use

A common community rationale. No published study has tested kisspeptin for this purpose.

4Reported side effects and interactions

Literature-reported

Well tolerated in all published human studies; no serious adverse events attributed. Transient injection-site reactions. No hot flushes or ovarian hyperstimulation signal.

Community-reported

flushing, headache, injection-site soreness, mood changes in both directions; reports of raised libido. Sparse, because most community use is of kisspeptin-10.

Theoretical. repeated frequent dosing is expected to desensitise the axis and could suppress rather than raise sex hormones; effects in people with hormone-sensitive cancers are unstudied; pregnancy safety unknown.

Interactions. GnRH and antagonists (triptorelin, leuprolide, cetrorelix, ganirelix) block or exhaust the downstream pathway; hCG and exogenous testosterone/oestrogen suppress the axis kisspeptin is trying to drive.

Markers researchers commonly monitor

Kisspeptin acts on the reproductive axis, so the markers are hormonal and timing matters (LH peaks within ~1 h of dosing):

Marker	Why it's watched
LH and FSH	the direct read-out of pituitary response; falling LH responses over repeated dosing indicate tachyphylaxis.
Total and free testosterone (men)	the downstream outcome; morning sample.
Oestradiol and progesterone (women)	cycle-phase dependent; useful only with the cycle day recorded.
Prolactin	the axis is sensitive to prolactin; a baseline rules out hyperprolactinaemia as a cause of low gonadotrophins.
SHBG	needed to interpret total testosterone.
Fasting glucose and insulin	one human study reports enhanced insulin secretion; worth a baseline.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Typically supplied in small vials (often 1–5 mg). Research doses are expressed in nmol/kg, so converting to micrograms requires the molecular weight (~5,857 g/mol for the amide); the calculator handles this. with , swirl gently, refrigerate.

Open in calculator, pre-loaded →

6Commonly studied alongside

Kisspeptin-10 (#45; shorter-acting fragment), gonadorelin and HCG (the compounds it is compared with for axis stimulation and IVF triggering), enclomiphene (community context, not a peptide), the GnRH analogues in this batch as comparators.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; investigational. Kisspeptin-10 was placed in FDA Category 2 of the compounding bulk-substances list (2023); whether that listing is read to cover kisspeptin-54 is unclear †
European Union	Not authorised; clinical trials only
United Kingdom	Not licensed; most human trials have been conducted here under research approvals
Australia	Not approved †
South Africa	Not registered †
Sport	WADA S2 lists kisspeptin and its agonist analogues as prohibited in males †

8Open questions

Can intermittent kisspeptin-54 (or a long-acting analogue) treat hypothalamic amenorrhoea or hypogonadism long term without desensitisation?
Will kisspeptin triggering reach clinical approval as a safer alternative to hCG in IVF?
Does the sexual-brain-processing effect translate into clinical benefit in desire disorders?
No data on long-term or community-pattern use.

9References

1Dhillo WS et al. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. PubMed · DOI
2Dhillo WS et al. (2007). Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J Clin Endocrinol Metab. PubMed · DOI
3Jayasena CN et al. (2009). Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab. PubMed · DOI
4Jayasena CN et al. (2013). Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea. Clin Pharmacol Ther. PubMed
5Jayasena CN et al. (2014). Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. PubMed · DOI
6Abbara A et al. (2015). Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of ovarian hyperstimulation syndrome during IVF therapy. J Clin Endocrinol Metab. PubMed · DOI
7Comninos AN et al. (2017). Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest. PubMed · DOI
8Mills EG et al. (2023). Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial. JAMA Netw Open. PubMed · DOI
9Izzi-Engbeaya C et al. (2018). The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans. Diabetes Obes Metab. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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