Kisspeptin
Also known as: Kisspeptin-54, Kisspeptin-10, Metastin, KiSS-1 Peptide, KP-54, KP-10
Kisspeptin is a neuropeptide that acts as the master upstream regulator of the HPG axis by directly stimulating GnRH neurons. Discovered in 2003, it controls puberty onset, LH pulsatility, and reproductive function. It is being researched for IVF triggering, hypogonadism, and as a physiological alternative to hCG and GnRH analogs.
Kisspeptin is a 1,302.45 Da (Kisspeptin-10) research peptide. Kisspeptin is a neuropeptide that acts as the master upstream regulator of the HPG axis by directly stimulating GnRH neurons. Discovered in 2003, it controls puberty onset, LH pulsatility, and reproductive function. It is being researched for IVF triggering, hypogonadism, and as a physiological alternative to hCG and GnRH analogs.
Also called: Kisspeptin-54, Kisspeptin-10, Metastin
1,302.45 (Kisspeptin-10)
Molecular Weight
Daltons
3
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
1600-12800
Typical Dose
mcg
Overview
Kisspeptin is a family of neuropeptides encoded by the KiSS-1 gene, acting through the kisspeptin receptor (KISS1R/GPR54) on GnRH neurons in the hypothalamus. The discovery in 2003 that loss-of-function mutations in KISS1R cause hypogonadotropic hypogonadism and absence of puberty established kisspeptin as the critical upstream gatekeeper of reproductive function. Kisspeptin neurons in the arcuate nucleus and anteroventral periventricular nucleus (AVPV) integrate metabolic, circadian, stress, and sex steroid signals to regulate GnRH pulsatility. The full-length peptide is Kisspeptin-54 (54 amino acids), but shorter fragments; Kisspeptin-10, -13, and -14, retain full receptor activity. Kisspeptin-10 (the C-terminal decapeptide) is most commonly used in research. Clinical trials have demonstrated kisspeptin can trigger oocyte maturation for IVF with dramatically reduced ovarian hyperstimulation syndrome (OHSS) risk compared to hCG triggers, making it particularly valuable for high-risk patients. Kisspeptin also stimulates LH pulsatility in men, with potential applications for testosterone optimization and fertility. Beyond reproduction, kisspeptin was originally identified as a metastasis suppressor (Metastin) and plays roles in emotional processing, mood, and sexual behavior.
Key Takeaways: Kisspeptin
- Strongest evidence supports Kisspeptin for ivf oocyte maturation trigger (reduced ohss) and physiological lh stimulation
- Research doses typically range from 1600 to 12800 mcg via subcutaneous injection (kp-54, single dose)
- 3 benefits with strong evidence, 2 moderate, 0 preliminary
- Half-life: ~28 minutes (KP-54 IV); ~4 minutes (KP-10 IV)
- 5 cited research studies in this guide
Mechanism of Action
Kisspeptin binds KISS1R (GPR54), a Gq/11-coupled GPCR expressed on GnRH neurons in the hypothalamus. Receptor activation triggers PLC/IP3/DAG signaling, increasing intracellular calcium and depolarizing GnRH neurons, causing GnRH secretion into the hypothalamic-pituitary portal system. Kisspeptin neurons exist in two critical populations: (1) the arcuate nucleus (ARC), where kisspeptin/neurokinin B/dynorphin (KNDy) neurons form the GnRH pulse generator — generating the rhythmic pulsatile GnRH release essential for LH/FSH secretion; and (2) the AVPV (in rodents) / rostral periventricular area (in humans), where kisspeptin neurons mediate the estrogen-positive feedback that triggers the preovulatory LH surge. This dual role makes kisspeptin both the tonic pulsatile driver of reproductive function AND the surge signal for ovulation. Kisspeptin neurons integrate inputs from metabolic sensors (leptin, ghrelin, insulin), circadian signals (SCN), stress hormones (cortisol/CRH), and sex steroids (estrogen, testosterone), explaining how nutrition, sleep, stress, and hormonal status all converge on reproductive function through this single neuropeptide node. In males, kisspeptin stimulates LH pulsatility and testosterone production. Importantly, kisspeptin triggers a physiological LH response (through GnRH) rather than the supraphysiological stimulation of hCG, which is why it carries lower OHSS risk in IVF.
Research Benefits
Kisspeptin at a Glance
Kisspeptin binds KISS1R (GPR54), a Gq/11-coupled GPCR expressed on GnRH neurons in the hypothalamus.
IVF Oocyte Maturation Trigger (Reduced OHSS)
Strong EvidenceClinical trials show kisspeptin effectively triggers oocyte maturation for IVF with dramatically reduced ovarian hyperstimulation syndrome risk compared to hCG, making it safer for high-risk patients.
Physiological LH Stimulation
Strong EvidenceStimulates endogenous GnRH release, producing physiological LH pulses rather than supraphysiological gonadotropin surges. Maintains normal HPG axis feedback mechanisms.
Puberty and Reproductive Axis Regulation
Strong EvidenceKisspeptin is the master gatekeeper of puberty; its activation initiates GnRH pulsatility at puberty onset. Therapeutic kisspeptin can activate the dormant HPG axis in hypogonadotropic hypogonadism.
Testosterone and Reproductive Function in Men
Moderate EvidenceResearch shows kisspeptin stimulates LH pulsatility and testosterone secretion in men, with potential applications for hypogonadism and fertility optimization.
Sexual Arousal and Behavior Enhancement
Moderate EvidencefMRI studies show kisspeptin enhances brain activity in regions associated with sexual arousal, attraction, and reward processing, suggesting direct effects on sexual behavior beyond hormone levels.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| IVF oocyte maturation trigger | 1600–12800 mcg | Subcutaneous injection (KP-54, single dose) |
| LH stimulation research (men) | 1000–10000 mcg | Subcutaneous injection (KP-54) |
| Kisspeptin-10 research protocol | 100–1000 mcg | Intravenous or subcutaneous |
Frequency
Single dose (IVF trigger); once or twice daily (LH stimulation research)
Timing
IVF: timed per stimulation protocol. Research: variable.
Cycle Length
Single administration (IVF); short-term research protocols (days to weeks)
Research Notes
- 1KP-54 (full-length) has longer half-life than KP-10 — preferred for clinical use.
- 2IVF trigger dose is a single SC injection timed 36 hours before egg retrieval.
- 3Kisspeptin triggers a physiological LH surge; not supraphysiological like hCG.
- 4Multiple Phase II trials completed for IVF; not yet commercially approved.
- 5Tachyphylaxis (reduced response) may occur with continuous exposure, pulsatile or intermittent dosing preferred.
- 6Active clinical trials at Imperial College London and other centers.
Reconstitution Guide
Standard Reconstitution
Vial Size
10 mg
Bacteriostatic Water
2 mL
Concentration
50 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
Kisspeptin vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 2 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Refrigerated (2-8°C) after reconstitution. Use promptly — limited stability data for reconstituted kisspeptin.
Storage Temperature
Refrigerated (2-8°C) after reconstitution
Shelf Life
Use promptly — limited stability data for reconstituted kisspeptin
Important Notes
- •Reconstitute with sterile water or bacteriostatic water.
- •KP-10 is less stable than KP-54.
- •Store lyophilized powder frozen (-20°C) for long-term storage.
- •Research-grade material, no commercial pharmaceutical formulation yet.
Kisspeptin Dosing Calculator
Calculate daily intake, cycle totals, and vials needed with pre-filled protocols →
Kisspeptin Reconstitution Calculator
Calculate concentration, syringe units, and doses per vial with auto-filled values →
Safety & Side Effects
Reported Side Effects
- !Injection site reactions
- !Flushing and warmth (common, related to GnRH/LH release)
- !Headache
- !Nausea (less common than with GnRH agonists)
- !Lower abdominal discomfort in females (related to ovarian response)
- !Very low OHSS risk compared to hCG trigger (primary safety advantage)
- !Generally well tolerated in clinical trials
- !Tachyphylaxis with continuous exposure (reduced efficacy, not a safety issue)
Potential Interactions
- ⚡GnRH agonists/antagonists: kisspeptin works upstream; effects may be blocked by GnRH antagonists.
- ⚡hCG: alternative IVF trigger — kisspeptin has lower OHSS risk.
- ⚡Gonadal steroids (testosterone, estrogen): provide negative feedback that modulates kisspeptin neuron activity.
- ⚡Leptin: metabolic signal that activates kisspeptin neurons; relevant for hypothalamic amenorrhea pathophysiology.
- ⚡Opioids: dynorphin (endogenous opioid) inhibits KNDy neurons, exogenous opioids may suppress kisspeptin-mediated LH release.
- ⚡Naltrexone: opioid antagonist that may enhance kisspeptin/GnRH pulsatility.
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
Kisspeptin as a novel IVF trigger: Phase II trial
Phase II trial demonstrating kisspeptin-54 effectively triggers oocyte maturation in IVF with zero cases of OHSS, compared to significant OHSS risk with hCG trigger in high-risk patients.
Loss-of-function mutations in GPR54 cause hypogonadotropic hypogonadism
Landmark discovery that KISS1R mutations cause failure of puberty and reproductive function, establishing kisspeptin as the essential upstream regulator of the HPG axis.
Kisspeptin enhances brain processing of sexual stimuli in men
fMRI study showing kisspeptin administration enhances activity in brain regions processing sexual and romantic stimuli, establishing direct kisspeptin effects on sexual behavior beyond hormonal changes.
Kisspeptin stimulates LH and testosterone in healthy men
Demonstrated kisspeptin-54 potently stimulates LH secretion and testosterone in healthy men through GnRH-dependent mechanisms, establishing its potential for male reproductive optimization.
KNDy neurons as the GnRH pulse generator
Established that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus form the GnRH pulse generator, the fundamental oscillator driving reproductive function.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
Kisspeptin is the master upstream neuropeptide controlling the HPG axis. It directly stimulates GnRH neurons to release GnRH, which drives LH/FSH secretion. It controls puberty onset, LH pulsatility, and reproductive function. It is being developed as a safer IVF trigger and for reproductive optimization.
Kisspeptin acts one step upstream — it stimulates GnRH neurons to release GnRH naturally, which then stimulates LH/FSH. Gonadorelin IS synthetic GnRH that acts directly on the pituitary. Kisspeptin produces a more physiological response because it works through the natural GnRH system.
hCG directly activates LH receptors with a long half-life (~36 hours), causing sustained, supraphysiological ovarian stimulation that can trigger OHSS. Kisspeptin triggers a short, physiological LH surge through endogenous GnRH, which self-limits. Clinical trials show zero OHSS with kisspeptin triggers vs significant OHSS risk with hCG.
Yes. Kisspeptin stimulates LH pulsatility, which drives testosterone production. Clinical studies show kisspeptin-54 produces strong LH and testosterone increases in healthy men. Research is exploring its potential for hypogonadism and fertility, though it is not yet approved for these indications.
Yes. Beyond its hormonal effects, fMRI studies show kisspeptin directly enhances brain activity in sexual arousal and reward circuits. This suggests kisspeptin influences sexual behavior through both hormonal (LH/testosterone) and direct neural pathways.
Kisspeptin is not yet commercially approved as a pharmaceutical. It is in active clinical trials, particularly for IVF triggering (Phase II completed with excellent results). Research groups at Imperial College London are leading clinical development.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.