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Hormonal & Sexual Health

Kisspeptin-10

Also known as KP-10, Kp-10, Kisspeptin 112-121, Metastin 45-54, KiSS-1 (112-121)

A ten-amino-acid fragment of the human kisspeptin protein that, given intravenously in small physiology studies, makes the hypothalamus fire a pulse of gonadotrophin-releasing hormone and so raises luteinising hormone and testosterone for a few hours.

How it works

The "master switch" of the reproductive axis; triggers natural release of LH and Testosterone by signaling the hypothalamus.

Performance edge

Essential for hormonal restoration research; studied for boosting libido and restoring natural testosterone.

Plain-English guide

Kisspeptin-10, without the jargon

What it is

Kisspeptin-10, often written KP-10, is the last ten amino acids of kisspeptin, a signalling protein made by the KISS1 gene in the hypothalamus, which is the part of the brain that controls hormone output. That short tail is the part that binds the receptor, so it behaves like the full-length molecule. Its job in the body is to switch on the neurons that release gonadotrophin-releasing hormone (GnRH), the pulse signal that tells the pituitary gland to put out luteinising hormone (LH) and follicle-stimulating hormone (FSH), which in turn tell the testes to make testosterone or the ovaries to mature an egg. Almost everything known about it in people comes from small hospital physiology studies, usually four to fifteen volunteers, in which it was given by intravenous drip or a single intravenous injection and blood hormones were sampled for a few hours. It is not an approved medicine anywhere, and the US Food and Drug Administration placed kisspeptin-10 on its list of bulk drug substances that may present significant safety risks in September 2023.

What people use it for

  • Raising luteinising hormone and testosterone in men, which a bolus of kisspeptin-10 does reliably over about 30 minutes (George 2011)
  • Investigating low testosterone in men with type 2 diabetes, where kisspeptin-10 still raised LH and testosterone, suggesting the pituitary and testes were working and the problem sat higher up (George 2013)
  • Mapping how the GnRH pulse generator is timed, since a single kisspeptin-10 bolus triggers an immediate LH pulse and resets the clock (Chan 2011)
  • Triggering egg maturation in fertility treatment and studying low sexual desire, though those trials used the longer kisspeptin-54 isoform rather than kisspeptin-10 (Mills 2023)
  • Off-label use in male hormone-optimisation circles as a testosterone-restoration or libido compound, which is not what any of the published trials were designed to test

How it works, simply

Think of your hormone system as a factory where the hypothalamus is the foreman, the pituitary is the dispatcher and the testes or ovaries are the production line. Testosterone injections skip the whole chain and drop finished product on the loading dock, which is why the foreman stops giving orders. Kisspeptin-10 goes to the other end and taps the foreman on the shoulder, so the order still travels down the normal chain. The catch found in the trials is that the tap is brief and the foreman stops responding if you keep tapping: repeated dosing desensitised the system rather than keeping it switched on (Jayasena 2009).

What to expect, and when

  1. Minutes 0-30In healthy men an intravenous bolus raised LH from about 4 to about 12 international units per litre by 30 minutes, with the largest response at 1 microgram per kilogram (George 2011).
  2. Hours 1-12During a continuous infusion, LH pulse frequency rose from roughly 0.7 to 1.0 pulses per hour and testosterone climbed from about 17 to 24 nanomoles per litre on the higher-dose infusion (George 2011). In men with type 2 diabetes an 11-hour infusion raised testosterone from about 8.5 to 11.4 nanomoles per litre (George 2013).
  3. Day 1Twice-daily subcutaneous kisspeptin-54 in women with hypothalamic amenorrhoea produced a large first-day rise in LH and FSH (Jayasena 2009).
  4. Days 2-14In that same study the response collapsed by day 14, from an LH rise of about 24 down to about 2.5 international units per litre, which the authors called tachyphylaxis, meaning the receptor stops answering with repeated dosing (Jayasena 2009).
  5. Beyond 2 wksNo human study located ran longer than about two weeks of repeated dosing, so there is no evidence base for the 8-to-12-week cycles used off-label, and no human data on what repeated subcutaneous kisspeptin-10 does to testosterone over months.

Side effects and interactions

  • The human studies located reported no adverse events; one 2025 paper states that kisspeptin had previously been given intravenously and subcutaneously to over 1000 people without any observed adverse effects, and that intranasal dosing was tolerated by all participants with no side effects of any severity (Mills 2025). That is not the same as none existing, because these were short exposures in screened volunteers
  • Loss of effect with repeated dosing is the best-documented problem: the gonadotrophin response fell sharply by day 14 of twice-daily subcutaneous injection in women (Jayasena 2009)
  • Predictable downstream hormone swings, since the intended action is a surge in LH, FSH and then testosterone or oestradiol; in women the effect depends heavily on cycle phase and was absent in the follicular phase in one study (Jayasena 2011)
  • The US Food and Drug Administration has stated that compounded drugs containing kisspeptin-10 may pose risk for immunogenicity for certain routes of administration, meaning an immune reaction raised against the peptide, and may have complexities with regard to peptide-related impurities and characterisation of the active ingredient
  • Injection-site reactions are not characterised in the human literature located, because nearly every human study used intravenous infusion or a single intravenous bolus rather than the repeated subcutaneous injection used off-label
  • Because published human exposure is short-duration and in the low thousands at most, uncommon or delayed adverse effects would not have been detected

Who should avoid it

  • You are pregnant, trying to conceive without medical supervision, or breastfeeding; kisspeptin acts directly on the reproductive axis and on placental function, and no reproductive safety data exists for self-administered kisspeptin-10
  • You have a hormone-sensitive cancer or a history of one, including prostate or breast cancer; raising LH, testosterone or oestradiol is the opposite of what androgen- or oestrogen-deprivation treatment is meant to do
  • You have an undiagnosed cause of low testosterone. Kisspeptin-10 was used in research precisely to tell hypothalamic causes from pituitary and testicular ones (George 2013); self-treating skips the workup that would find a pituitary tumour, haemochromatosis or sleep apnoea
  • You are a woman with irregular cycles, polycystic ovary syndrome or hypothalamic amenorrhoea and are not under a specialist; the female response to kisspeptin-10 depends on cycle phase and was absent in the follicular phase in one study (Jayasena 2011)
  • You are a competitive athlete under the World Anti-Doping Agency code; kisspeptin and its agonist analogues are named in section S2.2.1 of the 2026 Prohibited List as testosterone-stimulating peptides prohibited in males at all times
  • You are under 18, since this is the pathway that starts puberty, or you are not working with a physician who knows you are taking it and can monitor hormones

Common mistakes

  • Assuming the off-label dose maps onto the trial dose. Every human study located used intravenous dosing: single boluses of 0.01 to 3.0 micrograms per kilogram, or infusions of 0.1 to 1.0 nanomoles per kilogram per hour (George 2011, Narayanaswamy 2015). A 100 to 200 microgram subcutaneous injection is a different route with a different absorption profile, and nobody has published what it does.
  • Dosing frequently and expecting a sustained effect. The one repeated-dosing study located found the hormonal response nearly gone by day 14 (Jayasena 2009), so adding injections per week is the change most likely to make the compound stop working.
  • Treating kisspeptin-10 as a drop-in replacement for gonadorelin or human chorionic gonadotrophin alongside testosterone replacement therapy. When kisspeptin-10, kisspeptin-54 and GnRH were compared head to head in the same men, GnRH produced roughly three-fold higher LH and FSH than kisspeptin-10 (Narayanaswamy 2015).
  • Ignoring cycle phase in women. Kisspeptin-10 raised gonadotrophins in men and in women during the preovulatory phase but not in women during the follicular phase (Jayasena 2011), so a flat weekly schedule ignores the one variable that determined whether it worked.
  • Reconstitution and storage errors. Use bacteriostatic water, run it slowly down the vial wall and swirl rather than shake; keep the lyophilised powder cold and dark, refrigerate after reconstitution, and discard on the timeline your pharmacist gives instead of stretching a 10 mg vial over months at room temperature.

Deep research

What the literature actually shows

Mechanism

Kisspeptin-10 is the C-terminal decapeptide of kisspeptin, the product of the KISS1 gene, and is also written as kisspeptin 112-121 or metastin 45-54. The longer isoform kisspeptin-54 and the shorter kisspeptin-10 share this active C-terminus and act at the same G protein-coupled receptor, KISS1R, originally named GPR54. The receptor sits on gonadotrophin-releasing hormone (GnRH) neurons in the hypothalamus, which is why exogenous kisspeptin drives the reproductive axis from its topmost node rather than at the pituitary or the gonad.

The clearest human demonstration of that topology is the pulse-resetting experiment. In thirteen healthy men, a single intravenous kisspeptin bolus induced an immediate LH pulse regardless of when the previous endogenous pulse had occurred, and the induced pulses were larger than spontaneous ones, about 5.0 against 2.1 milli-international units per millilitre (Chan 2011). Dose-ranging work in healthy men found maximal LH stimulation at a 1 microgram per kilogram bolus, with LH rising from about 4.1 to 12.4 international units per litre at 30 minutes, and showed that infusion raised both LH pulse frequency and testosterone (George 2011).

Potency relative to the drug already used clinically is modest. A single-blinded, placebo-controlled comparison infused vehicle, kisspeptin-10, kisspeptin-54 or GnRH into healthy men at 0.1, 0.3 and 1.0 nanomoles per kilogram per hour. Serum LH and FSH were about three-fold higher during GnRH than during kisspeptin-10, and about two-fold higher than during kisspeptin-54, while the two kisspeptin isoforms behaved similarly to each other (Narayanaswamy 2015). The argument made for kisspeptin in that literature is not that it is stronger but that it stimulates the axis in a more physiological pattern, because it works through the person's own GnRH neurons.

The response is not uniform across people or across time. In women, kisspeptin-10 raised gonadotrophins during the preovulatory phase of the menstrual cycle but failed to do so during the follicular phase, while men responded throughout, which the authors described as sexual dimorphism in the response (Jayasena 2011). Repeated subcutaneous dosing desensitises the system: in women with hypothalamic amenorrhoea, twice-daily kisspeptin-54 produced an LH rise of about 24 international units per litre on the first injection and about 2.5 by day 14 (Jayasena 2009). Any model of chronic kisspeptin-10 use has to account for that tachyphylaxis, and no published study located has shown a dosing schedule that avoids it.

Strength of evidence

Limited human dataKisspeptin-10 itself has been given to humans in five published studies, including a single-blinded placebo-controlled head-to-head against GnRH, but every one used the intravenous route in four to twenty volunteers over hours, measuring hormone levels rather than clinical outcomes; the best-designed randomised trials in this list used the kisspeptin-54 isoform, and no published human study has given kisspeptin-10 subcutaneously at all, which is the route and schedule the cheatsheet dosing prescribes.

Key studies

  • Human trial2011The Journal of Clinical Endocrinology and Metabolismn = 6
    Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men

    Healthy men received intravenous kisspeptin-10 as boluses from 0.01 to 3.0 micrograms per kilogram and as infusions lasting up to 22.5 hours. Maximal LH stimulation occurred at 1 microgram per kilogram, rising from 4.1 to 12.4 international units per litre at 30 minutes. During lower-dose infusion LH pulse frequency rose from 0.7 to 1.0 pulses per hour, and testosterone rose from 16.6 to 24.0 nanomoles per litre during high-dose infusion.

  • Human trial2011The Journal of Clinical Endocrinology and Metabolismn = 13
    Kisspeptin resets the hypothalamic GnRH clock in men

    Thirteen healthy adult men received a single intravenous bolus of the kisspeptin C-terminal decapeptide. It induced an immediate LH pulse regardless of the timing of the previous endogenous pulse, and the induced pulses were larger than spontaneous ones, 5.0 against 2.1 milli-international units per millilitre. The authors read this as kisspeptin resetting the hypothalamic GnRH pulse generator.

  • Human trial2015Human Reproductionn = 15
    Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men

    Single-blinded, placebo-controlled study with five men per dosing group receiving three-hour intravenous infusions of vehicle, kisspeptin-10, kisspeptin-54 or GnRH at 0.1, 0.3 and 1.0 nanomoles per kilogram per hour. Serum LH and FSH were about three-fold higher during GnRH than during kisspeptin-10 and about two-fold higher than during kisspeptin-54; mean LH area under the curve was 34.06 hour-international units per litre for GnRH against 10.81 for kisspeptin-10. The two kisspeptin isoforms had comparable effects on gonadotrophin secretion.

  • Human trial2011The Journal of Clinical Endocrinology and Metabolism
    The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans

    Intravenous kisspeptin-10 was given to small groups of men and of women studied in different phases of the menstrual cycle, with four to five participants per group. It stimulated gonadotrophin release in men and in women during the preovulatory phase, but failed to stimulate gonadotrophin release in women during the follicular phase, indicating that the response depends on sex and on cycle phase.

  • Human trial2013Clinical Endocrinologyn = 12
    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

    Five men with type 2 diabetes and mild biochemical hypogonadism and seven healthy controls were studied. A 0.3 microgram per kilogram kisspeptin-10 bolus raised LH in the diabetic men from 4.7 to 10.7 international units per litre, and an 11-hour infusion at 4 micrograms per kilogram per hour in four of them raised testosterone from 8.5 to 11.4 nanomoles per litre. The authors took this as evidence that the defect in these men lies upstream of the pituitary and testes.

  • Human trial2009The Journal of Clinical Endocrinology and Metabolismn = 10
    Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis

    Ten women with hypothalamic amenorrhoea received twice-daily subcutaneous kisspeptin-54 at 6.4 nanomoles per kilogram, or saline, for two weeks. The first injection raised LH by 24.0 and FSH by 9.1 international units per litre, but by day 14 those rises had fallen to 2.5 and 0.5. The authors concluded that repeated dosing causes desensitisation, which limits chronic kisspeptin administration as a treatment. This study used the kisspeptin-54 isoform rather than kisspeptin-10.

  • Randomised controlled trial2023JAMA Network Openn = 32
    Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial

    Double-blind, two-way crossover, placebo-controlled trial in men with hypoactive sexual desire disorder; 37 were randomised and 32 completed. A 75-minute intravenous infusion of kisspeptin-54 at 1 nanomole per kilogram per hour modulated activity in sexual-processing brain structures, increased penile tumescence in response to sexual stimuli by up to 56 percent more than placebo, and increased self-reported happiness about sex. This trial used kisspeptin-54 by intravenous infusion, not subcutaneous kisspeptin-10.

  • Randomised controlled trial2025eBioMedicinen = 34
    Intranasal kisspeptin administration rapidly stimulates gonadotropin release in humans

    Twelve healthy men, twelve healthy women and ten patients with hypothalamic amenorrhoea received intranasal kisspeptin-54 at 12.8 nanomoles per kilogram, which significantly raised LH against placebo in all groups. The paper states that before this study kisspeptin had been given intravenously and subcutaneously to over 1000 healthy people and patients without any observed adverse effects, and that intranasal dosing was tolerated by all participants with no side effects or adverse events of any severity.

Safety data

The reported tolerability record is unremarkable and the exposure behind it is short. A 2025 paper from the main research group states that kisspeptin had been administered intravenously and subcutaneously to over 1000 healthy men and women and to patients with reproductive and psychosexual disorders without any observed adverse effects, and that intranasal administration produced no side effects or adverse events of any severity in any participant (Mills 2025). Almost all of that exposure consists of single boluses or infusions lasting hours, in screened volunteers, under hospital supervision. It cannot speak to repeated subcutaneous self-injection over weeks or months, which is how the compound is used off-label.

The most concrete adverse finding in the literature is loss of effect rather than harm. Twice-daily subcutaneous kisspeptin-54 in women with hypothalamic amenorrhoea produced a strong gonadotrophin response on day 1 and almost none by day 14 (Jayasena 2009). This matters for anyone using the off-label 8-to-12-week cycle, because the published data point toward the axis becoming unresponsive rather than toward a sustained testosterone gain, and no human study located has tested a schedule that avoids it. There is also no human data on what happens to the reproductive axis after stopping repeated dosing.

Product quality is a separate risk from the molecule. The US Food and Drug Administration added kisspeptin-10 to its list of bulk drug substances used in compounding that may present significant safety risks on 29 September 2023, stating that compounded drugs containing it may pose risk for immunogenicity for certain routes of administration, may have complexities with regard to peptide-related impurities and active-ingredient characterisation, and that the agency lacks sufficient information to know whether the drug would cause harm when administered to humans. Material bought outside a regulated supply chain carries the additional and unquantified risk of not being what the label says.

Regulatory status

FDA
As of 2026-09-19, kisspeptin-10 is not approved by the US Food and Drug Administration for any indication, is not a component of any FDA-approved drug, and has been listed since 29 September 2023 on the agency's page of bulk drug substances used in compounding that may present significant safety risks, citing immunogenicity risk and peptide impurity and characterisation concerns.
WADA
As of 2026-09-19, kisspeptin and its agonist analogues are named in section S2.2.1 of the World Anti-Doping Agency 2026 Prohibited List as testosterone-stimulating peptides in males, prohibited at all times both in and out of competition.
Source
https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks

Open questions

  • Does subcutaneous kisspeptin-10 at 100 to 200 micrograms do anything comparable to the intravenous boluses and infusions used in every human study located? No published pharmacokinetic or dose-response work for that route and dose was found.
  • Is there any dosing schedule that raises testosterone over weeks without the desensitisation seen by day 14 of twice-daily subcutaneous dosing (Jayasena 2009)? Intermittent weekly dosing has not been tested against that endpoint in humans.
  • Do the sexual-desire findings transfer from kisspeptin-54 given by intravenous infusion (Mills 2023) to kisspeptin-10 given subcutaneously at home? The isoform, the route and the setting all differ.
  • Why choose kisspeptin-10 over GnRH, which produced roughly three-fold higher LH and FSH in the same men (Narayanaswamy 2015) and exists as an approved drug? The claimed advantage of a more physiological pulse pattern has not been tested against a clinical outcome.
  • What are the effects of repeated kisspeptin-10 exposure on fertility, on the menstrual cycle in women outside the preovulatory window (Jayasena 2011), and on the axis after discontinuation? None of these has been followed beyond about two weeks in any published human study.