Kisspeptin-10 (Metastin 45-54)
A gene first identified as a metastasis suppressor, which became one of the central regulators of reproduction: the story of kisspeptin is one of the most unexpected in modern endocrinology.
- Research Use Only
- Molecule under study
- Living document
View the corresponding reference in the shop
- Current research state
- Experimental molecule — active academic clinical research, particularly by W. Dhillo's team (Imperial College London).
- Current clinical phase
- Exploratory clinical trials — no regulatory approval
- Last update
- 21 July 2026 · Reference fact sheet v1.0
- Living document
- Updated regularly as research progresses.
What is Kisspeptin-10 (Metastin 45-54)?
Kisspeptin is a family of peptides encoded by the KISS1 gene, initially identified as a metastasis suppressor before being recognized as a central regulator of reproduction.
Kisspeptin-10 corresponds to the 10 C-terminal amino acids (Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂), the minimal sequence retaining activity at the KISS1R receptor.
Since the discovery of its receptor (GPR54) in 2003, it has been studied as a key upstream regulator of puberty and reproductive function.
Names you may come across
This molecule may appear under several names in the scientific, clinical or technical literature. Here are the main designations you may come across.
Short bioactive fragment of 10 amino acids.
Common abbreviation in the scientific literature.
Former name associated with the metastasis-suppressor gene KISS1.
Understanding it simply
Three simple reference points for understanding Kisspeptin-10.
The master regulator of fertility
Without kisspeptin, GnRH neurons remain silent: the reproductive axis does not start functioning. This explains its central role in puberty.
An upstream signal
Kisspeptin-10 acts upstream of GnRH, and therefore of LH and FSH. This distinguishes it from conventional fertility treatments that act further downstream.
Pulsatility to be preserved
In men, KP-10 increases LH pulse frequency; prolonged exposure to kisspeptin can, however, desensitize the axis: the effect depends on dose and regimen.
What research shows today
Science advances step by step. We clearly distinguish what is firmly established from what remains under study.
- A 10-amino-acid peptide corresponding to the C-terminal end of human kisspeptin (KP-54). — established
- Selective agonist of the KISS1R (GPR54) receptor, expressed primarily on GnRH neurons. — established
- Documented stimulation of pulsatile GnRH release, followed by LH and FSH release. — established
- The optimal therapeutic role (fertility, amenorrhea, ovulation triggering) is under evaluation. — ongoing
- Data on long-term tolerability and optimal pharmacokinetics remain limited. — ongoing
Well-characterized central mechanism. The most advanced exploratory trials (hypothalamic amenorrhea, oocyte maturation in IVF) mainly used kisspeptin-54; data specific to KP-10 come from smaller physiological studies. No regulatory approval.
What the research shows
- Essential role of the KISS1/KISS1R pair in initiating and maintaining human reproductive function (demonstrated by loss-of-function mutations causing congenital hypogonadotropic hypogonadism).
- LH stimulation in humans described with both KP-54 and KP-10; in men, KP-10 increases LH pulse frequency (George et al., 2011).
- Trials triggering oocyte maturation in IVF conducted with kisspeptin-54 (Jayasena et al., 2014), with favorable reported tolerability; these data do not concern KP-10.
- Exploratory studies in women with hypothalamic amenorrhea and in men with hypogonadotropic hypogonadism, mainly with kisspeptin-54.
What still remains to be studied
- Large-scale direct comparison with GnRH analogues and hCG for ovulation triggering.
- Optimal use (dose, route, chronicity) for fertility indications.
- Possible extension to other fields (disorders of sexual desire, endometriosis, hormone-dependent cancer) — still preliminary.
What we know today
Not all information carries the same weight of evidence. We therefore present it across three clearly distinct levels, from the most solid to the most indicative.
What scientific publications show
Scientific evidence- Publications consistently support an essential role for kisspeptin in the human reproductive axis.
- Clinical studies (notably W. Dhillo's team) report LH stimulation, mostly with kisspeptin-54, with a favorable tolerability profile.
- Kisspeptin-54 has been studied as an IVF trigger in patients at risk of ovarian hyperstimulation, with few cases reported; these data are not large-scale comparative data and do not concern KP-10.
What some professionals report
Documented- Clinician authors highlight the relevance of an upstream, physiological action without prolonged stimulation.
- No official recommendations from reproductive medicine societies yet include Kisspeptin-10 in routine practice.
What the community reports
Field observations- Community reports are rare: Kisspeptin-10 remains confined to academic clinical research.
- Individual observations do not replace clinical trials.
The evidence is strong for the mechanism and exploratory for clinical applications.
How does Kisspeptin-10 (Metastin 45-54) work?
Kisspeptin-10 acts very far upstream in the reproductive hormonal cascade.
- KISS1R (GPR54) receptor
- G protein-coupled receptor expressed on GnRH neurons in the hypothalamus.
- GnRH neurons
- Activation of pulsatile GnRH release into the hypothalamic–pituitary portal system.
- Anterior pituitary
- Subsequent secretion of LH and FSH by gonadotroph cells.
- Gonads
- Stimulation of Leydig cells (testosterone) in men, and of granulosa and theca cells (estradiol, ovulation) in women.
Kisspeptin is now considered the principal upstream regulator of the GnRH pulse generator.
Clinical trials timeline
A molecule under study progresses step by step. Here, simply, is where the research currently stands.
- Discovery· 1996Completed
Identification of the KISS1 gene
The KISS1 gene is identified in Hershey (Pennsylvania) as a metastasis suppressor.
- Discovery· 2003Completed
Reproductive role of KISS1/GPR54
Two independent teams report that GPR54 mutations cause congenital hypogonadotropic hypogonadism, revealing the central role of the kisspeptin system in puberty.
- Clinical· 2005-2012Completed
First administrations in humans
Dhillo et al. describe LH stimulation by kisspeptin-54; later studies show an effect of KP-10 on LH in men.
- Clinical· 2014-2019Completed
Ovulation triggering in IVF
Trials evaluating kisspeptin-54 as a trigger of oocyte maturation, notably in patients at risk of ovarian hyperstimulation.
- Ongoing· CurrentlyOngoing
Exploratory extension
Clinical research on disorders of sexual desire, hypothalamic amenorrhea, and other hormonal axes — regular publications, no approval.
Available analyses
No analytical document has been published for this molecule to date.
Open the analysis libraryFrequently asked questions
Is Kisspeptin-10 an approved medicine?
No. It remains at the academic clinical research stage. PHL presents it for educational and reference purposes (Research Use Only).
How does it differ from full-length kisspeptin (KP-54)?
Established: KP-10 corresponds to the 10 C-terminal amino acids of KP-54 and retains activity at the KISS1R receptor. However, its plasma half-life is shorter.
Is it an “LH releaser”?
Established: yes, indirectly — by stimulating pulsatile GnRH release, which in turn triggers LH and FSH secretion by the pituitary.
Can it be used instead of hCG in IVF?
To be studied: published trials used kisspeptin-54, not KP-10. They suggest a potential benefit in patients at risk of hyperstimulation, but are not included in official guidelines.
Does it affect sexual desire?
To be studied: brain imaging studies conducted with kisspeptin-54 suggest modulation of desire-related regions; clinical evidence remains preliminary.
What adverse effects have been reported?
Established: published trials report generally favorable tolerability, with mainly injection-site reactions. Long-term tolerability remains poorly documented.
Scientific publications
Selected reference publications on kisspeptin and Kisspeptin-10. An evolving bibliography.
Glossary
- KISS1 / KISS1R (GPR54)
- The gene encoding kisspeptin and its receptor, essential for regulation of the reproductive axis.
- GnRH
- Gonadotropin-Releasing Hormone — a hypothalamic hormone that triggers LH and FSH secretion.
- LH / FSH
- Pituitary hormones regulating gonadal function (testes and ovaries).
- HPG axis
- Hypothalamic–pituitary–gonadal axis, the hormonal cascade regulating reproduction.
- FIV
- In vitro fertilization — an assisted reproductive technology.
- Hypothalamic amenorrhea
- Absence of menstruation associated with central inhibition of the GnRH pulse generator.
Continue your discovery
Read next
Sheets that are thematically close. These links serve reading and discovery — they suggest no combined use.
Reference fact sheet — version 1.0, updated on 21 July 2026. The full regulatory and scientific framework is gathered in the “Important information” box at the top of the fact sheet.