Kisspeptin
Kisspeptin-10 · KP-10 · Kisspeptin-54 · metastin
+56% penile rigidity vs placebo in men with HSDD (Comninos/Dhillo, 2023)
Overview
Kisspeptin is a neuropeptide encoded by the KISS1 gene that signals through the KISS1R receptor (formerly GPR54) and sits at the top of the reproductive hormone cascade. By stimulating hypothalamic gonadotropin-releasing hormone (GnRH) neurons, it drives downstream luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release — and, unusually for a reproductive hormone, it is also expressed in limbic brain regions involved in emotional and sexual processing, which is the basis of recent interest in low sexual desire.
Two main forms are studied. Kisspeptin-10 (KP-10) is the short C-terminal decapeptide with a very brief circulating half-life of roughly four minutes, while kisspeptin-54 (KP-54, the full-length metastin) lasts longer at around 28 minutes after subcutaneous dosing and is the form used in most landmark trials. Because the signal is pulsatile and continuous exposure causes the LH response to fade (tachyphylaxis), kisspeptin is given as discrete pulses or short cycles rather than continuously.
The most striking human data come from Imperial College London, where placebo-controlled crossover trials in men and women distressed by hypoactive sexual desire disorder (HSDD) found that a 75-minute kisspeptin-54 infusion enhanced activity in sexual-processing brain networks and, in men, increased penile rigidity by up to 56% versus placebo. These are mechanistic, single-session studies; there is no approved kisspeptin product and the figures below are provided strictly as a research reference.
Key parameters
- Dose range
- 50–200 mcg (KP-10, community); 1 nmol/kg/h IV (KP-54, trials)
- Frequency
- Once daily pulse (community) or single trial infusion
- Half-life
- KP-10 ~4 min; KP-54 ~28 min (subcutaneous)
- Route
- Subcutaneous (intravenous in clinical trials)
- Vial sizes
- 5 mg · 10 mg
- Regulatory status
- Investigational. No kisspeptin product is approved by any regulator for any indication. In October 2024 an FDA advisory committee voted against adding kisspeptin-10 to the 503A compounding bulks list. Research-vial material is labeled for laboratory use only.
Mechanism of action
KISS1R (GPR54) agonism on GnRH neurons
Binds the kisspeptin receptor on hypothalamic GnRH neurons, triggering pulsatile GnRH secretion that drives downstream LH and FSH release from the pituitary — the master 'on switch' of the reproductive axis.
Hypothalamic–pituitary–gonadal (HPG) axis modulation
By gating GnRH output upstream, kisspeptin can raise LH and, when the gonads are responsive, indirectly increase testosterone or estrogen. It does not replace sex hormones directly — it relies on a functioning downstream axis.
Limbic / sexual-processing brain activity
Kisspeptin receptors are expressed in limbic structures such as the amygdala and hippocampus. Functional-MRI studies show kisspeptin modulates activity in these sexual- and emotional-processing regions, which is thought to underlie its effects on arousal and desire independent of the pure hormonal cascade.
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Low-dose pulse (community) | Short cycle (2–4 weeks) | 50–100 mcg once daily (KP-10, subcutaneous) | Conservative community starting range; pulsed to limit desensitization. |
| Standard pulse (community) | Short cycle (4–6 weeks) | 100–200 mcg once daily (KP-10, subcutaneous) | Most-cited community window; some split as 100 mcg twice daily. |
| Clinical-trial infusion (KP-54) | Single session | 1 nmol/kg/h intravenously for 75 minutes | The dosing used in the Imperial HSDD fMRI trials — an acute research paradigm, not a home protocol. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
10 mg vial + 2 mL bacteriostatic water
Concentration5,000 mcg/mL · 5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 50 mcg | 0.01 mL | 1 |
| 100 mcg | 0.02 mL | 2 |
| 200 mcg | 0.04 mL | 4 |
Common community mix; the small draws below assume a U-100 syringe and benefit from a fine 0.3 mL barrel.
10 mg vial + 5 mL bacteriostatic water
Concentration2,000 mcg/mL · 2 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 50 mcg | 0.025 mL | 2.5 |
| 100 mcg | 0.05 mL | 5 |
| 200 mcg | 0.1 mL | 10 |
More dilute mix that makes the small microgram doses easier to measure accurately.
Reconstitution calculator
Pre-filled with Kisspeptin's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 2,500 micrograms per millilitre, a 50 microgram dose is 0.02 millilitres, or 2 units on a U-100 syringe, giving 100 doses per vial.
This draw is only 2 units — small volumes are hard to measure accurately. Consider using less bacteriostatic water to make each dose a larger, easier-to-read draw.
Supplies needed
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Recommended supply
Kisspeptin — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
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Bacteriostatic water
Diluent for reconstituting lyophilized vials.
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Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
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Alcohol prep pads
Sterile swabs for the vial stopper and site.
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Sharps container
Safe disposal of used needles.
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Storage fridge
Keeps reconstituted vials at 2–8 °C.
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Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
No approved-label guidance exists because kisspeptin is investigational. Because the peptide is short-acting and used in pulses, a missed community dose is generally skipped and the schedule resumed the next day rather than doubled. Clinical trials administer single fixed infusions, so 'missed dose' handling does not apply in that setting.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Dermatologic | Mild flushing or warmthReported shortly after dosing; mild and transient in trials. | — |
| Injection site | Local redness or irritation | — |
| Neurological | Transient headache | — |
| Gastrointestinal | Brief mild nausea | — |
| Endocrine | Tachyphylaxis (fading LH response with continuous exposure)The main pharmacologic limitation; the rationale for pulsed/short-cycle dosing rather than continuous use. | — |
Clinical trials & evidence
Kisspeptin in men with HSDD (Imperial College)
Phase 2 (mechanistic RCT)Two single-session visits ≥7 days apart · 32 heterosexual men with HSDD (mean age ~38)
KP-54 infusion increased penile rigidity by up to 56% vs placebo and significantly modulated sexual-processing brain networks (Cohen d ≈ 0.81).
ISRCTN17271094 ↗Kisspeptin in women with HSDD (Imperial College)
Phase 2 (mechanistic RCT)Two single-session visits · 32 premenopausal women with HSDD
KP-54 infusion increased activity in sexual-arousal brain regions and reduced activity in inhibition/aversion regions vs placebo; no significant adverse events.
Trial identifier needs verification
Kisspeptin-54 IVF oocyte maturation (Hammersmith)
Phase 2Single trigger dose per cycle · Women at high risk of ovarian hyperstimulation syndrome (OHSS)
Single/second-dose KP-54 triggered oocyte maturation with LH peaking ~5 h and returning to baseline by ~12–14 h; explored as a lower-OHSS-risk alternative to hCG.
Trial identifier needs verification
Storage & handling
- Lyophilized
- Store lyophilized powder frozen at −20 °C for long-term stability; short-term refrigeration at 2–8 °C is acceptable. Protect from light.
- Reconstituted
- Refrigerate at 2–8 °C and use within ~28 days. Do not freeze the reconstituted solution; discard if cloudy or discolored.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| PT-141 (Bremelanotide) | KISS1R (upstream of GnRH) vs melanocortin MC4R | KP-10 ~4 min / KP-54 ~28 min vs ~2.7 h | 50–200 mcg pulse or IV infusion vs 1.75 mg as needed | Boosts sexual brain processing (investigational) vs approved for HSDD | Investigational vs FDA-approved (Vyleesi) |
| Oxytocin | KISS1R / reproductive axis vs oxytocin receptor (bonding) | Minutes vs minutes | Subcutaneous pulse / IV vs mostly intranasal | Hormonal + sexual-processing effects vs social/affiliative effects | Investigational vs IV-approved (obstetrics), off-label otherwise |
Sources & references
- [1]Mills EG et al. Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With HSDD: A Randomized Clinical Trial. JAMA Netw Open 2023. ↗ source
- [2]Comninos AN et al. Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest 2017. ↗ source
- [3]Kisspeptin hormone injection could treat low sex drive in women and men — Imperial College London. ↗ source
Frequently asked questions
What does kisspeptin do in the reproductive axis?
It acts on the KISS1R receptor on GnRH neurons, sitting at the very top of the reproductive cascade. By driving GnRH it raises LH and FSH and, when the gonads are responsive, can indirectly raise testosterone or estrogen. It is not testosterone replacement — it depends on a functioning downstream axis.
What is the difference between kisspeptin-10 and kisspeptin-54?
Both activate the same receptor. Kisspeptin-10 is the short decapeptide with a roughly four-minute half-life; kisspeptin-54 (metastin) is the full-length peptide that lasts longer (around 28 minutes subcutaneously) and is the form used in most published HSDD and IVF trials.
Is kisspeptin FDA-approved?
No. As of 2026 there is no FDA-approved kisspeptin product for any indication, and an FDA advisory committee voted in 2024 against adding kisspeptin-10 to the 503A compounding bulks list. The human data are from mechanistic research studies only.
Related protocols
PT-141 (Bremelanotide)
Bremelanotide
FDA-approved (2019) for premenopausal hypoactive sexual desire disorder
Oxytocin
OXT
Endogenous bonding nonapeptide; large autism trial (SOARS-B) found no benefit over placebo
Melanotan II
MT-II
Non-selective melanocortin agonist (tanning + libido); the precursor context for PT-141
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For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.