Section 01
What it's used for
Reproductive Hormone Testing
Kisspeptin-10 tests brain-level reproductive signaling. In six healthy men, IV doses of 0.01-3.0 microg/kg raised LH to 12.4 IU/L; half-life is only 4 minutes. Effects vary sharply by sex and cycle, in small studies of 4-10 volunteers.
▸Clinical wording
Because kisspeptin acts upstream of GnRH neurons, an intravenous kisspeptin-10 bolus probes hypothalamic rather than pituitary function. In six healthy men, intravenous boluses of 0.01–3.0 µg/kg produced dose-dependent LH rises peaking at about 12.4 IU/L thirty minutes after the 1 µg/kg dose, and a 1.5 µg/kg/h infusion raised LH pulse frequency from 0.7 to 1.0 pulses per hour, with no adverse events recorded. Responses are markedly sex- and cycle-dependent: kisspeptin-10 raised LH and FSH in men and in preovulatory-phase women, but produced no gonadotropin change in follicular-phase women even at intravenous boluses up to 10 nmol/kg. Its plasma half-life is roughly 4 minutes — about seven-fold shorter than kisspeptin-54 — which suits it to acute stimulation testing rather than sustained treatment; all of these are small single-centre human physiology studies with four to ten volunteers per arm.
Amenorrhea Treatment Research
Treatment trials for missed periods used kisspeptin-54, not kisspeptin-10. Its only evidence: two women, where a 12-hour infusion raised LH from 5.3 to 25.4 IU/L. No study showed restored periods or pregnancy with kisspeptin-10.
▸Clinical wording
The human treatment trials in hypothalamic amenorrhoea used kisspeptin-54, not kisspeptin-10: five women given 8–10 hour intravenous infusions (0.01–1.00 nmol/kg/h) had a three-fold higher peak LH pulse count and a six-fold higher peak pulse secretory mass than on vehicle, and twice-weekly subcutaneous kisspeptin-54 for 8 weeks raised reproductive hormones while twice-daily dosing caused tachyphylaxis. The only kisspeptin-10 evidence in chronic amenorrhoea is an exploratory report in two women with cabergoline-resistant hyperprolactinaemic amenorrhoea, in whom a 12-hour infusion at 1.5 µg/kg/h raised mean serum LH from 5.3 to 25.4 IU/L with increased LH pulse frequency. No study has shown restored menstruation, ovulation or pregnancy with kisspeptin-10 itself, and the relevant sample sizes are two to five patients.
IVF Trigger Research
Every published IVF trigger trial used kisspeptin-54, since kisspeptin-10's 3-4 minute half-life is too short. Three phase 2 trials, one London center, reported live-birth rates of 20.4%, 45.1%, and 30%. Kisspeptin-10 itself was untested.
▸Clinical wording
Every published trial of kisspeptin as an oocyte-maturation trigger has used kisspeptin-54, because kisspeptin-10's terminal half-life of roughly 3–4 minutes is too short to drive a sustained LH surge. Three phase-2 trials, all from one London centre, reported live-birth rates per embryo transfer of 20.4% (n = 53), 45.1% (n = 60 women at high risk of ovarian hyperstimulation syndrome) and 30% (n = 62), with no moderate or severe OHSS in the first two trials and one case (1.6%) in the third. Kisspeptin-10 itself has not been tested as an IVF trigger, so this direction reflects the kisspeptin class rather than this specific peptide, and the evidence remains phase-2 and single-centre.
Puberty Disorder Diagnosis
In 16 youths with delayed puberty, one kisspeptin-10 injection correctly predicted who would go through puberty (P=.0002), with 100% sensitivity and specificity. It beat standard tests, but the study was small and cut-offs are unvalidated.
▸Clinical wording
Kisspeptin-10 is being investigated as a test to distinguish constitutional delay of puberty from permanent hypogonadotropic hypogonadism. In a prospective cohort of 16 youths (13 boys, 3 girls) with delayed or stalled puberty, a single 0.313 µg/kg intravenous bolus separated the groups completely: all eight with an LH rise of 0.8 mIU/mL or more later progressed through puberty and all eight with a rise of 0.4 mIU/mL or less reached age 18 without pubertal signs (P = .0002; sensitivity and specificity 100%, 95% CI 74–100%), outperforming GnRH-stimulated LH, inhibin B and genetic testing. An earlier report from the same group in 15 children found the same bimodal split, and in 25 healthy boys studied across Tanner stages an intravenous kisspeptin-10 bolus produced a significant LH rise only at Tanner stage V, indicating that KISS1R responsiveness matures late in puberty. These cohorts are small and single-centre, and the proposed diagnostic cut-offs have not yet been validated in an independent population.
Diabetes-Related Low Testosterone
In five men with type 2 diabetes and mild low testosterone, plus seven healthy men, kisspeptin-10 raised LH pulse frequency from 0.6 to 0.9 per hour and raised testosterone. With only five patients, this shows mechanism, not treatment.
▸Clinical wording
In a proof-of-concept study, five men with type 2 diabetes and mild biochemical hypogonadism plus seven age-matched healthy men received kisspeptin-10; LH pulse frequency rose from 0.6 to 0.9 pulses per hour, with accompanying increases in LH secretion and serum testosterone. The authors read this as evidence that the low testosterone in these men originates upstream of the GnRH neuron rather than in the pituitary or testis. With five patients, a single centre and only acute dosing, this is a physiological observation about mechanism, not evidence that kisspeptin-10 treats hypogonadism.
Section 02
Mechanism of Action
Locking onto the fertility receptor
- It is the short tail-end of a larger protein and keeps its full activity.
- Reported binding figures make it the tighter binder of the family, ahead of kisspeptin-54.
- Occupying the receptor frees calcium inside the cell through a standard signalling cascade.
- In mouse brain slices, blocking that cascade cut responding neurons from about 80 percent to 15.
▸Clinical wording
KISS1R coupling to Gq/11 and phospholipase C
Kisspeptin-10 is the C-terminal decapeptide of the KISS1 gene product and the shortest fragment retaining full intrinsic activity at KISS1R (GPR54); in binding studies it is the higher-affinity ligand of the family, with a reported Ki near 0.042 nM against 0.34 nM for kisspeptin-54. KISS1R is a Gq/11-coupled receptor: occupancy activates phospholipase C, which hydrolyses PIP2 into IP3 and DAG, mobilising intracellular calcium and activating protein kinase C. In mouse brain slices, blocking PLC or the IP3 receptor cut the share of GnRH neurons responding to kisspeptin from about 80 percent to 15 and 7 percent respectively.
Making fertility neurons fire
- In mouse neurons the peptide shifted the cell's electrical charge by up to about 22.6 millivolts.
- Two things happen together: one potassium channel closes while a sodium-passing channel opens.
- Blockers of that second channel type stopped the current, while another blocker did not.
- Single-cell testing found the matching channel genes present in these neurons.
▸Clinical wording
TRPC-like cation channels and Kir closure in GnRH neurons
The calcium cascade converges on membrane conductances. In mouse GnRH neurons kisspeptin produced concentration-dependent depolarisation up to about 22.6 mV with an EC50 near 2.8 nM. The underlying inward current reversed close to -115 mV, more negative than the potassium equilibrium potential, because two events occur together: barium-sensitive inwardly rectifying (Kir) potassium channels close while sodium-dependent non-selective cation channels open. The current was blocked by TRPC blockers such as 2-APB, flufenamic acid and SKF96365 but not by lanthanum, and single-cell RT-PCR detected TRPC1 and TRPC3-7 transcripts in these neurons.
Two parallel routes to one signal
- A second signal runs through two arms that overlap in time.
- In knockout cells the peak response needed both arms, appearing within minutes then fading.
- The two versions of one arm act oppositely: losing one weakened signalling, losing the other strengthened it.
- Even in cells missing the first arm the peptide still altered over 1,600 gene probes.
▸Clinical wording
ERK1/2 activation through parallel Gq/11 and β-arrestin arms
Alongside the calcium arm, KISS1R drives ERK1/2 phosphorylation through two routes that overlap in time. In knockout mouse embryonic fibroblasts and in the GT1-7 hypothalamic neuronal line with arrestin knockdown, maximal ERK phosphorylation required both Gαq/11 and β-arrestin-2, was detectable within 2.5 minutes and peaked at 5-10 minutes before declining. The two arrestin isoforms act oppositely: losing β-arrestin-2 sharply reduced signalling, while losing β-arrestin-1 enhanced it. Nuclear as well as cytosolic pERK accumulation depended on both arms, and in Gαq/11-null cells kisspeptin still altered 1,635 probe sets more than twofold.
Setting the tempo of reproductive hormones
- Neurons in one brain region form the pulse generator pacing reproductive hormone release.
- In healthy men, intravenous peptide raised luteinising hormone within 30 minutes, dose by dose.
- Continuous infusion sped pulses from about 0.7 to 1.0 per hour and raised testosterone.
- A direct pituitary effect appears in rat cell cultures but far below the brain route.
▸Clinical wording
Pulsatile GnRH drive and gonadotroph output
Kisspeptin neurons of the arcuate nucleus co-express neurokinin B and dynorphin, the KNDy population that acts as the GnRH pulse generator, neurokinin B accelerating and dynorphin braking it. In healthy men, intravenous kisspeptin-10 raised serum LH dose-dependently within 30 minutes, and continuous infusion increased LH pulse frequency from about 0.7 to 1.0 pulses per hour, enlarged secretory bursts and raised testosterone; infused kisspeptin-54 raised the same three hormones. A smaller direct pituitary component exists: in peripubertal rat pituitary cultures kisspeptin-10 raised cytosolic calcium in gonadotrophs and somatotrophs and stimulated LH release, far below the GnRH response.
The receptor switching itself off
- Sustained exposure uncouples the receptor and pulls it inside the cell.
- Most of it is resensitised and recycled back, keeping a working pool at the surface.
- The peptide clears fast, with a half-life near 3 minutes against about 28 for kisspeptin-54.
- In men the largest single dose gave a smaller response than an intermediate one.
▸Clinical wording
Receptor desensitisation, internalisation and recycling
Sustained agonist exposure switches KISS1R off. GRK2 phosphorylation and β-arrestin recruitment uncouple the receptor from Gαq/11 and pull it into clathrin-coated pits; most internalised receptor is resensitised and recycles to the surface, keeping a signalling-competent pool, while a minority is routed to degradation. This desensitisation is homologous and rapid rather than a consequence of GnRH depletion. Pharmacokinetics interacts with it: kisspeptin-10 has a terminal half-life near 3 minutes against roughly 28 minutes for kisspeptin-54, and in men the highest bolus produced a smaller LH response than an intermediate one, although a prolonged infusion did not induce tachyphylaxis.
Section 03
Biological Pathways
No data for this section yet.
Section 04
Dosage Information
Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Intravenous drip — LH pulse studies | Dose-finding in healthy men; LH is a fertility hormone | 0.1, 0.3, 1.0 nmol/kg/h for 3 h, 5 men each; also 1.5 µg/kg/h for 9 h and 4 µg/kg/h for 22.5 h (~1.2 and 3.1 nmol/kg/h), 4 men each | The drip is not for convenience: blood half-life is about 4 minutes, so LH pulses shift only while the pump runs. It measured hormone timing, not any outcome. |
| Intravenous — single injection | Immediate LH response in 6 healthy men | 0.01–3.0 µg/kg as a single injection — about 0.008–2.3 nmol/kg; the LH response peaked at 1 µg/kg and rose no further above it | Six men, one injection, one hormone measured. In blood the peptide sat below the test's detection limit at almost every sample, so even the exposure is unknown. |
| Intravenous — brain-imaging trials | Brain scans of sexual response — kisspeptin-54 | 1 nmol/kg/h for 75 minutes, in 29–33 healthy men and in men and women with low sexual desire | The libido findings pinned on kisspeptin-10 came from a different molecule, with a 27.6-minute half-life against its 4 minutes. The dose does not carry across. |
| Subcutaneous — self-administration | Circulating practice, no human trial by this route | 100–200 µg per injection, spaced rather than daily; some sources go to 500 µg–1 mg — about 1.1–14 µg/kg for a 70–90 kg adult | Not a smaller version of the research: under the skin, a peptide that clears in minutes is absorbed slowly and unevenly — the opposite of those infusions. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Lyophilised powder
In a human clinical study the freeze-dried vials were stored at −20 °C and reconstituted in 0.5 ml of 0.9% sodium chloride. The reagent supplier claims up to 6 months for the lyophilised form at 0–5 °C and advises rehydrating it just before use.
After reconstitution
The solution is kept at 4 °C for up to 5 days, or frozen at −20 °C for up to 3 months after being split into aliquots, so that it is not put through repeated freeze-thaw cycles.
Section 07
Side Effects & Precautions
Kisspeptin has an unusually large human safety record, but most of it belongs to kisspeptin-54, not kisspeptin-10. Kisspeptin-10's own human footprint is a handful of small studies, and only one, with 16 participants, has a published adverse-event table.
Large serious-event dataset belongs to kisspeptin-54
- The biggest human dataset comes from an IVF program using kisspeptin-54, not kisspeptin-10.
- Across a 175-participant study, serious adverse events included 6 ectopic pregnancies, 7 miscarriages, 1 heterotopic pregnancy and 1 stillbirth.
- These were attributed to IVF and pregnancy, not to the peptide.
- In the 53-patient trial within that program, three implantation-site abnormalities occurred: two ectopic and one heterotopic pregnancy.
- The study's own authors flagged that rate as needing larger studies.
Kisspeptin-10's own adverse-event record is thin
Most kisspeptin-10 human studies report no formal adverse-event data at all. The only kisspeptin-10 trial with a posted adverse-event table, in 16 participants, recorded zero serious adverse events on kisspeptin or placebo, with bruising, headache and fatigue occurring at similar rates on both.
Continuous dosing can flip the hormonal effect
- Frequent or continuous kisspeptin dosing desensitizes its receptor, flipping stimulation into suppression.
- Continuous kisspeptin-10 infusion in agonadal juvenile male monkeys raised hormones briefly, then fell sharply.
- Twice-daily kisspeptin-54 caused the same in women with hypothalamic amenorrhea; twice-weekly dosing was only partial.
Testicular toxicity in prepubertal rats
- In prepubertal rats, twice-daily kisspeptin-10 injections for 12 days lowered LH and testosterone at higher doses.
- The same injections caused seminiferous tubule degeneration, including tubular necrosis and vacuolization.
- A companion study found severe degeneration of the seminal vesicles, with dose-dependent DNA damage.
Special populations are essentially unstudied
No published study has given kisspeptin to pregnant women or people with liver or kidney impairment. Pediatric exposure to kisspeptin-10 is limited to one low intravenous dose in 15 children with delayed puberty; several registered kisspeptin trials are completed without posted results.
Section 08
Regulatory Status
Two decades of clinical research have not produced a marketed drug, and international anti-doping rules already treat it as a prohibited hormone-class substance.
FDA / United States
Not approved for any indication
The Pharmacy Compounding Advisory Committee voted against adding kisspeptin-10 to the 503A bulk drug substances list at its 29 October 2024 meeting, where it had been nominated for secondary hypogonadism in men; members cited insufficient evidence of efficacy and safety. No NDA or BLA for kisspeptin-10 exists on the FDA record.
WADA
Prohibited under category S2
Kisspeptin was added as a named example under S2 — Peptide Hormones, Growth Factors, Related Substances and Mimetics — on the 2024 WADA Prohibited List. The ban applies to every competing athlete at all times, in and out of competition, because kisspeptin drives supraphysiological release of luteinising hormone and, in men, testosterone.
Clinical research
Studied in humans since 2005
Investigators at Imperial College London gave intravenous and subcutaneous kisspeptin-10 to healthy volunteers from the mid-2000s onward to map its effect on LH and FSH release (Jayasena et al., 2011). A related trigger built from the longer kisspeptin-54 isoform reached a completed phase II trial for oocyte maturation in IVF (NCT01667406); separate US phase I studies used the identical 10-residue fragment under the name kisspeptin 112-121 (NCT00914823, NCT05633966). None of this clinical work has produced an approved product.
Neither the FDA nor the EMA has approved a kisspeptin-10 product for any indication, and regulatory status differs between countries and changes over time — check the current guidance of your own regulator and anti-doping authority before relying on this summary.
Section 09
Research Studies
- [1]Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channelsLiu X, Lee K, Herbison AE. · Endocrinology · 2008
- [2]Kisspeptin depolarizes gonadotropin-releasing hormone neurons through activation of TRPC-like cationic channelsZhang C, Roepke TA, Kelly MJ, Rønnekleiv OK. · The Journal of Neuroscience · 2008
- [3]GPR54 regulates ERK1/2 activity and hypothalamic gene expression in a Gαq/11 and β-arrestin-dependent mannerSzereszewski JM, Pampillo M, Ahow MR, Offermanns S, Bhattacharya M, Babwah AV. · PLoS ONE · 2010
- [4]Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in menGeorge JT, Veldhuis JD, Roseweir AK, Newton CL, Faccenda E, Millar RP, Anderson RA. · The Journal of Clinical Endocrinology & Metabolism · 2011
- [5]Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human malesDhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR. · The Journal of Clinical Endocrinology & Metabolism · 2005
- [6]Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatotrophs and stimulation of luteinising hormone and growth hormone secretionGutiérrez-Pascual E, Martínez-Fuentes AJ, Pinilla L, Tena-Sempere M, Malagón MM, Castaño JP. · Journal of Neuroendocrinology · 2007
- [7]The emerging therapeutic potential of kisspeptin and neurokinin BPatel B, Koysombat K, Mills EG, Tsoutsouki J, Comninos AN, Abbara A, Dhillo WS. · Endocrine Reviews · 2024
- [8]The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproductionXie Q, Kang Y, Zhang C, Xie Y, Wang C, Liu J, Yu C, Zhao H, Huang D. · Frontiers in Endocrinology · 2022
Section 10
Frequently Asked Questions
In men, an intravenous dose of kisspeptin-10 reliably raises luteinising hormone within 30 minutes in a dose-dependent way, and a small proof-of-concept study in men with type 2 diabetes and mild hypogonadism showed both LH pulse frequency and testosterone rising with it — evidence that some low-testosterone states originate upstream of the pituitary. But this is acute hormone stimulation, not a measured fertility outcome: no study has shown kisspeptin-10 itself restores ovulation, menstruation or pregnancy, and the response is strongly sex- and cycle-dependent — it produced no gonadotropin rise at all in follicular-phase women even at high intravenous doses.
Fast, but briefly. Its plasma half-life is about 4 minutes, and a single intravenous injection produces a measurable rise in luteinising hormone within 30 minutes that plateaus — doses above about 1 µg/kg raised LH no further. Because it clears so quickly, any effect tracks the injection itself rather than building over days, which is why research infusions keep the pump running continuously rather than dosing once.
Essentially all the human evidence comes from intravenous dosing — single injections from 0.01 to 3.0 µg/kg, or continuous infusions in the 0.1 to 3 nmol/kg per hour range — chosen because the roughly 4-minute half-life demands a steady drip to sustain a hormone effect. The subcutaneous self-administration figures circulating outside research, commonly 100 to 200 µg per injection, are not a smaller version of that protocol: injected under the skin, a peptide that clears in minutes is instead absorbed slowly and unevenly, the pharmacological opposite of the infusions that were actually studied.
This has not been established. No side-effect data for kisspeptin-10 is available in the reviewed record — the human studies were small, single-dose or short-infusion physiology experiments, as few as six volunteers, focused on hormone measurements rather than safety monitoring, and no safety profile has been compiled from them.
There is no recorded regulatory status for kisspeptin-10 — it has not been evaluated as an approved drug and no FDA or equivalent approval exists. It remains a research and diagnostic compound studied in small clinical physiology trials, not a marketed medicine.
They're related but pharmacologically distinct, and it matters clinically: kisspeptin-10's half-life is roughly 4 minutes against kisspeptin-54's 27.6 minutes, a seven-fold difference. Every study needing a sustained hormone effect — treating hypothalamic amenorrhoea, triggering egg maturation in IVF, or the brain-imaging studies of sexual response — used kisspeptin-54, not kisspeptin-10, precisely because kisspeptin-10 clears too fast to sustain those effects.
In the one clinical study to specify it, freeze-dried kisspeptin-10 was stored at −20 °C and reconstituted in saline shortly before use; a reagent supplier separately claims up to 6 months at 0–5 °C for the lyophilised form. Once reconstituted, it is kept at 4 °C for up to 5 days or frozen in single-use portions at −20 °C for up to 3 months, avoiding repeated freeze-thaw cycles.