Kisspeptin-10

KP-10, metastin (45–54), kisspeptin 112–121, KISS1 peptide; the full-length form is kisspeptin-54 (metastin)

Longevity & cellular

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Summary

Class: Naturally occurring 10-amino-acid fragment of kisspeptin, a hormone encoded by the KISS1 gene; acts on the kisspeptin receptor (KISS1R, formerly GPR54)
Mechanism: Fires the hypothalamic GnRH neurons, which release LH and FSH from the pituitary, which in turn drive testosterone or oestrogen and ovulation — it sits one step above GnRH in the reproductive axis
Routes studied: Intravenous bolus and infusion, subcutaneous bolus and infusion (human physiology studies); intranasal (one study); subcutaneous (community)
Dose range reported: Human studies: IV bolus 0.24–10 nmol/kg; subcutaneous bolus 1–6.4 nmol/kg (kisspeptin-54, roughly 6–40 µg/kg); IV infusion 4 µg/kg/h (kisspeptin-10) for up to 22.5 hours; twice-weekly 6.4 nmol/kg subcutaneous kisspeptin-54 for 8 weeks in women. Community: 50–200 µg subcutaneous, often 2–3 times weekly. No approved dose
Half-life: Kisspeptin-10: ~4 minutes in circulation; kisspeptin-54: ~28 minutes. Effects on LH last 1–2 hours after a bolus
Storage: Lyophilised: refrigerate. Reconstituted: refrigerate; community practice within ~2–4 weeks (the decapeptide is less stable than many peptides)
Regulatory status: Not approved anywhere; investigational; FDA Category 2 compounding listing (2023)

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

1What it is

Kisspeptin is a hormone the body already makes. The KISS1 gene — named by researchers in Hershey, Pennsylvania (home of Hershey's Kisses) who first found it as a tumour-suppressor in 1996 — produces a 54-amino-acid peptide that is cut into shorter active forms, of which kisspeptin-10 is the smallest. In 2003 two groups showed that people born without a working kisspeptin receptor do not go through puberty, which revealed kisspeptin as the master switch of the reproductive hormone axis (Seminara 2003; de Roux 2003). It is also expressed in the placenta (blood levels rise thousands-fold in pregnancy) and in brain regions involved in emotion and sexual processing.

As a research compound kisspeptin-10 is the synthetic copy of that natural fragment. Human work has come mainly from Imperial College London (Dhillo, Jayasena, Comninos) and from fertility groups testing kisspeptin-54 as a safer trigger for egg maturation in IVF. The community interest is in using it to raise testosterone or restore natural LH output without suppressing the axis, and for libido.

2How it's thought to work

Hypothalamus. kisspeptin neurons in the arcuate and preoptic nuclei synapse directly onto GnRH neurons. KISS1R activation depolarises them and causes GnRH release, which within minutes raises LH (and, less, FSH) from the pituitary.

Pulse generator. together with neurokinin B and dynorphin ("KNDy" neurons), kisspeptin sets the rhythm of GnRH pulses. Continuous high-dose exposure desensitises the system — in men infused with kisspeptin-10 for over 22 hours LH stayed elevated, but in women given kisspeptin-54 twice daily for 2 weeks the LH response faded (Jayasena 2009).

Oestrogen feedback. kisspeptin neurons carry oestrogen receptors and translate the pre-ovulatory oestrogen surge into the LH surge.

Limbic brain. functional MRI shows kisspeptin alters activity in the amygdala and other regions during sexual and emotional tasks (Comninos 2017).

Metastasis suppression and placenta. the original KISS1 role; not relevant to community use but the reason "metastin" appears as a synonym.

Kisspeptin neurons fire the GnRH neurons, which make the pituitary release LH and FSH; these drive the testes or ovaries.Schematic — not to scale

3What the research shows

Stimulates LH and testosterone in healthy men

IV bolus kisspeptin-10 produced dose-dependent LH rises within 15–30 minutes, and a 22.5-hour infusion raised LH and testosterone throughout (George 2011, J Clin Endocrinol Metab). Kisspeptin-54 and IV gave similar results (Dhillo 2005, J Clin Endocrinol Metab). Short, small, physiological studies. [3][6]

Stimulates LH in women

Responses depend on cycle phase: largest in the pre-ovulatory phase, small in the follicular phase (Dhillo 2007; Jayasena 2011). Twice-weekly kisspeptin-54 for 8 weeks in women with hypothalamic amenorrhoea raised LH without desensitisation; twice-daily dosing did desensitise (Jayasena 2009, 2010 — J Clin Endocrinol Metab). [4][5]

Hypogonadotropic hypogonadism

Kisspeptin-10 infusion restored LH pulsatility in men with hypogonadism due to type 2 diabetes (George 2013, Diabetes Obes Metab). Men with mutations below the kisspeptin receptor (e.g. GnRH receptor defects) do not respond; those with low kisspeptin signalling (e.g. anorexia, hyperprolactinaemia) can (Chan 2011; Sonigo 2012, J Clin Invest — hyperprolactinaemia in mice and later women). [7]

Graded B/A (small RCT phases)

IVF egg maturation trigger

Kisspeptin-54 as the final "trigger" injection in IVF produced mature eggs and live births, with markedly less ovarian hyperstimulation syndrome than hCG in women at high risk of OHSS (Jayasena 2014, J Clin Invest; Abbara 2015, J Clin Endocrinol Metab). Phase 2 scale; Phase 3 pending. [8][9]

Sexual and emotional brain processing, libido

In double-blind crossover fMRI studies in healthy men, kisspeptin-54 infusion increased limbic activity in response to sexual and bonding images and improved mood scores (Comninos 2017, J Clin Invest). In men with HSDD, kisspeptin increased penile tumescence and brain responses to sexual stimuli (Mills 2023, JAMA Netw Open); in women with HSDD, a parallel study showed altered brain activation and modestly increased self-reported sexual arousal (Thurston 2022, JAMA Netw Open). Experimental infusions in a laboratory, not treatment trials. [10][11][12]

Diagnostic test for puberty disorders

A kisspeptin stimulation test has been studied to distinguish delayed puberty from permanent hypogonadism (Chan 2020, J Clin Endocrinol Metab).

Testosterone replacement alternative, "PCT", body composition

No trial has used kisspeptin for these purposes. Community use rests on the physiology above.

4Reported side effects and interactions

Literature-reported

generally well tolerated in hundreds of research-study exposures; no serious adverse events reported in healthy volunteers. Injection-site reactions, occasional flushing and mild nausea. Tachyphylaxis (fading response) with continuous or very frequent dosing. Transient rises in LH, FSH, testosterone or oestradiol are the intended effect but mean the hormone profile shifts for hours.

Community-reported

increased libido, mood lift, improved erections, flushing, headache, slight nausea, injection-site itching; some report no noticeable effect at low doses.

Theoretical. in people with hormone-sensitive conditions (prostate cancer, oestrogen-dependent cancers, endometriosis) stimulating the axis is undesirable. Desensitisation with overuse could in theory lower rather than raise output. Very high kisspeptin levels occur naturally in pregnancy, so pregnancy itself is not a toxicity concern, but no one has studied exogenous dosing in pregnancy.

Interactions. GnRH /antagonists and hormonal contraceptives alter or block the response; exogenous testosterone or anabolic steroids suppress the axis, so kisspeptin's effect would be blunted. Opioids and high prolactin suppress kisspeptin neurons.

Markers researchers commonly monitor

Marker	Why it's watched
LH and FSH	the direct read-out of the effect, best measured 30–60 minutes after a dose and at baseline.
Total and free testosterone (men) or oestradiol and progesterone (women)	the downstream outcome; timing relative to dosing matters.
Sex hormone-binding globulin	helps interpret total testosterone.
Prolactin	high prolactin blunts the response; a baseline helps explain a non-response.
Haematocrit and PSA (men)	standard when testosterone is being raised by any route.
Menstrual cycle tracking and ovulation markers (women)	kisspeptin can advance or trigger ovulation.

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

5Reconstitution and handling

Usually supplied as 5 mg or 10 mg vials. with , swirl, keep cold. Short peptides with free ends degrade faster than cyclic ones; community practice is to make smaller batches.

Open in calculator, pre-loaded →

6Commonly studied alongside

Gonadorelin and HCG (the next two steps down the same axis — often compared, sometimes alternated in community protocols); clomiphene and enclomiphene (different mechanism, same aim); PT-141 (sexual-function research line); neurokinin B and NK3 receptor antagonists (fezolinetant — the hot-flush drug — works on the KNDy neurons).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; placed in Category 2 of FDA's bulk drug substances list for compounding (2023), restricting compounding
European Union	Not authorised; investigational
United Kingdom	Not licensed; used in research under clinical trial authorisation
Australia	Not approved †
South Africa	Not registered †
Sport (WADA)	Not named; as a non-approved substance it falls under S0, and anything that raises testosterone may be relevant to S1/S2 interpretation †

8Open questions

Does intermittent kisspeptin raise testosterone durably in men without desensitising the system? Only days-to-weeks data exist.
The right dosing rhythm to avoid tachyphylaxis.
Whether the brain effects on sexual processing translate into clinical benefit for HSDD.
Kisspeptin-54 vs kisspeptin-10: the human data are split between the two forms.

9References

1Seminara SB et al. (2003). The GPR54 gene as a regulator of puberty. N Engl J Med. PubMed · DOI
2de Roux N et al. (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. DOI
3Dhillo WS et al. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. PubMed · DOI
4Dhillo 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
5Jayasena 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
6George JT et al. (2011). Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. PubMed · DOI
7George JT et al. (2013). Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism. Diabetes Obes Metab. PubMed · DOI
8Jayasena CN et al. (2014). Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. PubMed · DOI
9Abbara A et al. (2015). Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) therapy. J Clin Endocrinol Metab. PubMed · DOI
10Comninos AN et al. (2017). Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest. PubMed · DOI
11Thurston L et al. (2022). Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial. JAMA Netw Open. PubMed · DOI
12Mills 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
13FDA (2023). Bulk drug substances for compounding — kisspeptin-10 category 2 listing. PubMed

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

25 Oct 2026Profile published — awaiting medical review

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