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Kisspeptin-10 (KP-10)

Kisspeptin receptor (KISS1R) agonist

Also known as Metastin 45-54, KP-10

The upstream trigger of the reproductive axis, with genuine ongoing academic human research. One of the more scientifically respectable entries at this end of the ladder.

Guide updated Sep 2, 2026Literature checked Sep 2, 20261 curated study33 literature recordsBaseline editorial

Overview

In shortThe peptide that sits at the very top of the chain controlling reproductive hormones. Its discovery reshaped the field, because people born with a broken version of its receptor never go through puberty. Unlike most unapproved entries here, it is the subject of active, well-conducted academic research, particularly in fertility medicine.

Kisspeptin is the peptide that sits at the top of the hypothalamic-pituitary-gonadal axis. It stimulates GnRH release, which drives LH and FSH, which drive the gonads. Its discovery reshaped reproductive endocrinology, because loss-of-function mutations in its receptor cause failure of puberty.

Unlike most unapproved entries here, it is the subject of active, well-conducted academic human research, particularly from groups working on reproductive disorders and IVF trigger protocols.

Mechanism

In shortIt acts on neurons in the hypothalamus, which release the signal that tells the pituitary to release the reproductive hormones, which in turn drive the gonads. Because it works at the very top of that chain, it keeps the natural rhythm and feedback intact in a way that injecting the hormones directly does not. This particular fragment is the shortest active piece and lasts only minutes.

Kisspeptin binds KISS1R on GnRH neurons in the hypothalamus, stimulating pulsatile GnRH secretion. That produces LH and FSH release from the pituitary and downstream gonadal steroid production.

Because it acts upstream of GnRH, it preserves the pulsatility and feedback of the axis in a way that direct gonadotropin administration does not, which is the mechanistic argument for using it as an ovulation trigger.

Kisspeptin-10 is the shortest active fragment and has a short half-life, on the order of minutes.

Evidence

In shortEarly human work in defined research settings. Studies show it reliably triggers the hormone release it should, and it has been tested as an ovulation trigger in IVF with apparently less risk of dangerous overstimulation. For raising testosterone or restarting a suppressed system there is no properly sized evidence, and its minutes-long half-life makes sustained-effect claims implausible.

Early clinical, in defined research settings. Human studies have established that it reliably stimulates LH release, and it has been investigated as an ovulation trigger in IVF, with results suggesting a lower risk of ovarian hyperstimulation syndrome than conventional triggers.

Additional academic work explores its role in sexual and emotional brain processing.

For the uses discussed in community settings, boosting testosterone or restarting a suppressed axis in healthy adults, there is no adequately powered controlled evidence. The very short half-life also makes any sustained-effect claim mechanically implausible without a delivery strategy nobody has described.

Safety

In shortShort human research use has been well tolerated, with headache the most reported effect, but those were single or short courses in supervised settings. There is no data on repeated or ongoing use, and adjusting the top of the reproductive system without monitoring is an obvious place for unintended hormonal consequences.

Short human research exposure has been well tolerated, with headache the most reported effect.

The exposures studied are single or short-course administrations in supervised settings. There is no data on repeated or chronic use, and manipulating the top of the reproductive axis without monitoring is an obvious place for unintended endocrine consequences.

No long-term safety data. Not manufactured to pharmaceutical standards when purchased as a research chemical.

Regulatory status

In shortNot approved for anything. Investigational in academic research, and sold separately as a research chemical.

Not approved for any indication. Investigational in academic clinical research. Sold separately as a research chemical.

The literature

1 study indexed. Findings and limitations get equal weight, on purpose.

Always check the primary source

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The Kisspeptin-10 literature needs an account

Everything above is free to read. What an account opens is the evidence underneath it: 1 study with their limitations, and the regimen each trial actually reported.

  • Every study, with what it found and what it cannot show
  • The limitations, given the same weight as the findings
  • The dose each named trial administered, where recorded
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The wider literature

16 indexed papers and 17 registered trials mentioning Kisspeptin-10, straight from PubMed and ClinicalTrials.gov. 17 of 17 administer it; the rest measure it. These have not been read by us. Unlike the studies above, they carry no findings and no limitations written by anyone here, because writing either would mean claiming a reading nobody has done. They are a starting point for yours.

Registered trials (17)

  1. Kisspeptin to Quantify GnRH Neuronal Function in Health and Disease

    Stephanie B. Seminara, MD2026NCT07224490

    interventionalphase1recruitingn=40

  2. Kisspeptin Administration Subcutaneously to Patients With Hypothalamic Amenorrhea

    Stephanie B. Seminara, MD2025NCT07224438

    interventionalphase2recruitingn=20

  3. Kisspeptin Administration Subcutaneously to Patients With IHH

    Stephanie B. Seminara, MD2023NCT05896293

    interventionalphase2recruitingn=36

  4. Recall by Genotype: Neuropeptide Stimulation

    Stephanie B. Seminara, MD2023NCT05901467

    interventionalphase1terminatedn=16

  5. Dampening the Reproductive Axis With Continuous Kisspeptin

    Stephanie B. Seminara, MD2023NCT05971849

    interventionalphase1completedn=8

  6. Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders

    Stephanie B. Seminara, MD2022NCT05633966

    interventionalphase1completedn=13

  7. Evaluation of Kisspeptin Stimulated Insulin Secretion With Hyperglycemic Clamp

    Massachusetts General Hospital2022NCT05456854

    interventionalphase1withdrawnn=0

  8. Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Physiologic Mixed Meal Tolerance

    Stephanie B. Seminara, MD2019NCT04532801

    interventionalphase1withdrawnn=0

  9. Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism

    Stephanie B. Seminara, MD2019NCT04648969

    interventionalphase2completedn=18

  10. Administration of Kisspeptin in Patients With Hyperprolactinemia

    Massachusetts General Hospital2017NCT02956447

    interventionalphase2completedn=36

  11. Neuropeptides in Human Reproduction

    Massachusetts General Hospital2014NCT01952782

    interventionalphase1completedn=61

  12. Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys.

    Ghulam Nabi2014NCT03286517

    interventionalphase3completedn=30

  13. Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men

    Quaid-e-Azam University2014NCT03315325

    interventionalphase3completedn=15

  14. Kisspeptin in the Evaluation of Delayed Puberty

    Massachusetts General Hospital2013NCT01438034

    interventionalphase1completedn=24

  15. KP-10 and Insulin Secretion in Men

    Quaid-e-Azam University2013NCT03771326

    interventionalphase3completedn=14

  16. Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling

    Massachusetts General Hospital2011NCT01438073

    interventionalphase1completedn=96

  17. Kisspeptin Administration in the Adult

    Massachusetts General Hospital2009NCT00914823

    interventionalphase1completedn=256

Papers (16)

  1. Endocrine-metabolic effects of kisspeptin in mammals.

    Pastor FM, et al.General and comparative endocrinology2026PMID 41581529

    journal articlereviewresearch support, non-u.s. gov't

  2. Synthesis and characterisation of DOTA-kisspeptin-10 as a potential gallium-68/lutetium-177 pan-tumour radiopharmaceutical.

    Kleynhans J, et al.Journal of neuroendocrinology2025PMID 39775975

    journal articleresearch support, non-u.s. gov't

  3. Oral Engineered Extracellular Vesicles Based on Ion Exchange Strategy for Multipronged Management of Wilson's Disease Complicated with Reproductive Dysfunction Therapy.

    Wang T, et al.Advanced science (Weinheim, Baden-Wurttemberg, Germany)2025PMID 40673828

    journal article

  4. Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems.

    Marino M, et al.International journal of molecular sciences2025PMID 40362219

    journal article

  5. Kisspeptin-10 Improves Testicular Redox Status but Does Not Alter the Unfolded Protein Response (UPR) That Is Downregulated by Hypothyroidism in a Rat Model.

    Santos LC, et al.International journal of molecular sciences2024PMID 38338793

    journal article

  6. Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor.

    Shen S, et al.Cell reports2024PMID 38935498

    journal articleresearch support, non-u.s. gov't

  7. Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.

    Li Z, et al.Nature communications2024PMID 38346942

    journal articleresearch support, non-u.s. gov't

  8. Investigating the detection of the novel doping‐relevant peptide kisspeptin‐10 in urine using liquid chromatography high‐resolution mass spectrometry.

    Colpaert T, et al.Biomedical chromatography : BMC2024PMID 38978171

    english abstractjournal article

  9. Author Correction: Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.

    Li Z, et al.Nature communications2024PMID 39702286

    published erratum

  10. Role of kisspeptin-10 and betacellulin in control of feline ovarian cell functions.

    Loncová B, et al.Reproductive biology2023PMID 37058773

    journal article

  11. Safety Evaluation of KP-10 (Metastin 45-54) Following once Daily Intravenous Administration for 14 Days in Dog.

    Terse PS, et al.International journal of toxicology2021PMID 34126799

    journal articlerandomized controlled trial, veterinaryresearch support, n.i.h., extramural

  12. KISS1 in breast cancer progression and autophagy.

    Ulasov IV, et al.Cancer metastasis reviews2019PMID 31705228

    journal articleresearch support, non-u.s. gov'treview

  13. Kisspeptin and Cancer: Molecular Interaction, Biological Functions, and Future Perspectives.

    Ciaramella V, et al.Frontiers in endocrinology2018PMID 29662466

    journal articlereview

  14. Cross-Linking Furan-Modified Kisspeptin-10 to the KISS Receptor.

    Vannecke W, et al.ACS chemical biology2017PMID 28714670

    journal articleresearch support, non-u.s. gov't

  15. Kisspeptins and the placenta: regulation of trophoblast invasion.

    Hiden U, et al.Reviews in endocrine & metabolic disorders2007PMID 17351756

    journal articleresearch support, non-u.s. gov'treview

  16. GPR54 and kisspeptin in reproduction.

    Tena-Sempere MHuman reproduction update2006PMID 16731583

    journal articleresearch support, non-u.s. gov'treview

Discussion

Kisspeptin-10 has its own forum, split by the same six categories as the rest of the site.

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Research & Literature1Peptide Science0Experiences & Logs0Protocol Discussion0Safety & Harm Reduction0General Community0
Research & LiteratureDiscussion

What happened to the terminated Kisspeptin-10 trials?

Kisspeptin 10 is a Kisspeptin receptor (KISS1R) agonist. 14 of 28 records administer it, and…

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For Research & Educational Discussion Only. Not Medical Advice

This guide is educational reference material compiled from published literature. It is not medical advice, not a recommendation, and not a substitute for a clinician who knows your history. Nothing here should be used to make a decision about your own health without one.

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