Kisspeptin
Kisspeptin-10 · KP-10 · Metastin
Kisspeptin (KISS-1) is the absolute primordial trigger of the mammalian Hypothalamic-Pituitary-Gonadal (HPG) axis, effectively acting as the upstream master switch for human reproduction and endocrinology. Distinct from hCG or Enclomiphene, it is deployed in elite integrative endocrinology to aggressively upregulate endogenous testosterone production, reverse hypogonadism, and preserve massive gonadal volume without inducing estrogenic side effects or risking HPTA shutdown. It represents the cleanest, most physiologically natural method of restoring a suppressed hormonal baseline.
Use-case scores
0–10 against the evidence we have, not a gym ranking. Hidden domains do not apply here.
- Sexual / hormonal5/10
Kisspeptin-54/10 stimulate GnRH/LH in human physiology studies. Not an HSDD or TRT replacement NDA. Small-human: 5 after haircut vs approved hormones.
Compound card
- Class
- KISS1-derived RF-amide (metastin; reproductive research)
- Formula
- Variable - Kisspeptin-10 is the most studied fragment (10 amino acids)
- Status
- Not FDA-approved · research use
How it works
Kisspeptin is a neuropeptide encoded by the KISS1 gene that acts as the master upstream regulator of the reproductive hormone cascade. It activates GPR54 (KISS1R) receptors on hypothalamic GnRH neurons, triggering pulsatile GnRH release which drives LH and FSH secretion.
Kisspeptin sits at the very top of the HPG axis - above GnRH itself. Loss-of-function mutations in KISS1 or GPR54 cause hypogonadotropic hypogonadism (failure to enter puberty). Exogenous kisspeptin is studied as a diagnostic tool for reproductive disorders and as a therapeutic for functional hypothalamic amenorrhea (FHA), male hypogonadism, and polycystic ovary syndrome (PCOS). Because it acts upstream of GnRH, it can restart the entire reproductive cascade from the top down.
Source: PMID: 16140907
Background & History
Kisspeptin is a 54-amino-acid peptide encoded by the KISS1 gene, first identified in 1996 as a metastasis suppressor by Danny Welch at Pennsylvania State University. Its role as the master regulator of the hypothalamic-pituitary-gonadal (HPG) axis was discovered in 2003 independently by multiple groups who found KISS1 receptor mutations caused hypogonadotropic hypogonadism. Kisspeptin neurons directly activate GnRH neurons - it is upstream of GnRH in the reproductive endocrine hierarchy. It integrates metabolic status, stress, and environmental cues to regulate fertility and sexual function.
Research Use Cases
- ✓Identity: KISS1/metastin vs kisspeptin-10 vs GnRH vs hCG
- ✓Human LH-pulse papers are not a TRT replacement
- ✓Not Vyleesi and not a fertility protocol on this site
Dosing
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Diagnostic / Research | 0.01 - 1 mcg/kg | Single IV or SC dose for stimulation testing | Used diagnostically to test hypothalamic-pituitary axis integrity. Not an ongoing therapy at these doses. |
| Therapeutic Research | 1 - 3 nmol/kg IV | Pulsatile (every 90 min in research protocols) | Clinical trial protocol for FHA and reproductive disorders. Requires medical supervision. |
Administration
Timeline
Who it is for
Reproductive Endocrinology
ModerateStrong evidence for LH/FSH stimulation. In clinical trials for FHA and hypogonadism.
HPG Axis Restart / PCT
LowStudied for post-cycle testosterone restoration. Experimental - less established than triptorelin or gonadorelin for PCT.
Reconstitution
| Vial | Water | Concentration | Example dose |
|---|---|---|---|
| 5 mg lyophilized | 2 mL BAC | 2.5 mg/mL | Research mcg on the vial COA. Fertility-clinic protocols are not community SubQ folklore. |
Change vial size or water volume? Open the reconstitution calculator.
Safety & Considerations
Endogenous neuropeptide with clinical trial safety data. Short half-life limits systemic exposure. May cause transient facial flushing. Chronic pulsatile delivery requires IV access - not practical outside clinical research. Not yet FDA-approved for therapeutic use.
Regulatory & Legal Status
Competitive athletes subject to anti-doping controls should not use Kisspeptin.
Research Chemical
US Compounding: Not eligible / not available
⚠️ This information is for educational purposes only and may not reflect the most current regulatory updates. Always verify with official FDA, WADA, and jurisdiction-specific sources before use.
Limits of current evidence
- Kisspeptin-10 is a shorter SKU. Do not mix the dose tables.
- This site will not treat infertility or hypogonadism from this page.
Verdict
Kisspeptin sits upstream of GnRH. Human LH-pulse papers exist. It is not testosterone, not hCG, and not Vyleesi. Fertility-clinic research is not a libido stack.
Interactions & Contraindications
Kisspeptin pulses are required for efficacy - continuous GnRH output leads to downregulation. Exogenous testosterone suppresses kisspeptin neurons (negative feedback) - less effective while on TRT. Elevated estrogen also provides negative feedback. Leptin deficiency blunts kisspeptin response (anorexia, extreme caloric restriction).
Synergies & Common Stacks
Upstream KISS1R vs direct GnRH analog. Different rungs. Not a complete HPG cascade and not a fertility protocol on this site.
Kisspeptin is GnRH/LH. PT-141 is central MC4R. Clinics pair them. That is not a combination trial and not a sexual-health NDA.
Appears in goal guides
Goal guides are maps, not clinic protocols. A mention here is not a treatment plan.
Sexual Health & Libido Restoration
PT-141 is Vyleesi for premenopausal HSDD. Kisspeptin is upstream GnRH biology. This page maps the SKUs. It is not a PDE5 and not a general ED or libido NDA.
Perimenopause & Menopause Optimization
Kisspeptin, Epitalon, MOTS-c, and PT-141 as they show up next to menopause folklore. Not HRT and not a vasomotor-symptom indication.
Post-Cycle Endocrine Restoration (HPTA)
Educational PCT map: Testoluten, Libidon, Glandokort, plus Enclomiphene and Kisspeptin. Not a license to run steroids. Physician-owned.
Frequently Asked Questions
How is Kisspeptin different from Gonadorelin?▼
Can Kisspeptin be used for PCT?▼
References
- Dhillo WS et al. “"Kisspeptin-10 and LH secretion in humans".” Journal of Clinical Endocrinology & Metabolism (2005). PMID: 16131585
- Seminara SB, et al. “Kisspeptin signaling in the HPG axis.” N Engl J Med (2003). PMID: 14573733
- Dhillo WS, et al. “Kisspeptin as a diagnostic tool and therapeutic target in reproductive disorders.” Neuroendocrinology (2012). PMID: 22538355
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