Kisspeptin
Research OnlyAn endogenous neuropeptide that serves as the master regulator of reproductive function. Acts upstream of GnRH to control puberty, fertility, and the menstrual cycle. Under clinical investigation as a safer IVF trigger and treatment for hypothalamic amenorrhea. Pioneering research led by Imperial College London.
KISS1 · Metastin · Kisspeptin-54 · Kisspeptin-10 · KP-54 · KP-10
18 human studies
- Preclinical
- 25%
- Clinical
- 75%
Based on 24 cited sources
clinically demonstrated · moderate confidence
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 69: 1A=28 (>=2 double-blind RCTs — Abbara 2015 dose-finding n=60 26192876, Abbara 2017 Phase 2 n=62 28854728, Comninos 2017 n=29 28112678, Mills 2023 n=37 36735255 — but all single-centre/one group, no systematic review or meta-analysis of RCTs); 1B=15 (low-RoB blinded RCTs on the relevant outcome, no AMSTAR-rated review); 1C=6 (total human N ~250, 50-300 band); 1D=13 (direct population/route/outcome for IVF trigger and HA); 1E=7 (substantial multi-species preclinical program). Mechanism 95: 2A=40 (KISS1R/GPR54 named target with binding + functional confirmation + genetic knockout abolishing the effect in mouse and human GnRH deficiency); 2B=28 (full KISS1R->Gq/11->PLC->Ca2+->GnRH->LH/FSH->gonadal-steroid pathway characterized); 2C=17 (human dose-response 26192876 plus in-vivo animal gradients); 2D=10 (confirmed in-vivo incl. humans). Plausibility 87: 3A=33 (mechanism->surrogate LH pulsatility 24517142->clinical oocyte/pregnancy outcome chain supported; sexual-desire application 36735255 more surrogate-bound); 3B=24 (fully coherent with reproductive neuroendocrinology); 3C=17 (GnRH agonists/hCG reliably reproduce the analogous HPG effect); 3D=13 (tightly scoped to the reproductive axis). Global Coverage 73: 4A=22 (clinical trigger RCTs concentrated at Imperial, but kisspeptin/KISS1R biology independently replicated worldwide — Podfigurna/Genazzani Poland-Italy 32915434, plus US, Brazil, Spain, China); 4B=22 (UK, US, Poland, Italy, Japan, China, Brazil, Spain); 4C=24 (>100 studies, large and growing literature); 4D=5 (no regulatory approval; under trial registration NCT/ISRCTN). Community Experience 36: 5A=6 (negligible self-experimentation, clinical-research context only — dossier notes "very limited community experience"); 5B=8 (short track record outside the clinic); 5C=11 (limited but broadly consistent themes); 5D=11 (no recurring adverse signal, though exposure is small). Effectiveness basis clinical (moderate): primary IVF-trigger indication — E1=22 (95% oocyte maturation with zero OHSS vs significant OHSS for hCG; second-dose RCT +26% oocyte-yield), E2=17 (meaningful zero-OHSS plus competitive pregnancy/live-birth), E3=13 (hard patient-relevant outcomes — oocyte yield, pregnancy, OHSS avoidance), E4=14 (non-inferior maturation vs hCG with a safety edge, no head-to-head live-birth superiority); confidence moderate (RCTs small, single-centre, no meta-analysis).
Kisspeptin is the master regulator of reproduction, acting as the upstream controller of the entire hypothalamic-pituitary-gonadal axis. Human clinical trials have established its physiological role and therapeutic potential.
How It Works (Simplified)
Kisspeptin serves as the gatekeeper of fertility by directly activating GnRH neurons:
Binds KISS1R on GnRH neurons, triggering Gq/11-coupled signaling cascade that causes calcium mobilization and GnRH release.
GnRH stimulates pituitary gonadotrophs to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in physiological pulses.
Kisspeptin neurons express estrogen and progesterone receptors, integrating sex steroid feedback to regulate ovulation timing.
Unlike hCG, kisspeptin produces a short-lived LH surge (hours vs days), eliminating ovarian hyperstimulation syndrome risk in IVF.
Key Research: Abbara A et al. (Imperial College London, 2017) demonstrated kisspeptin-54 as safe IVF trigger with zero OHSS cases. PMID:28854728
Important Limitations
- Clinical trials primarily conducted by single research group (Imperial College London)
- Long-term safety data not yet available
- Optimal dosing regimens still being refined
- Continuous administration causes tachyphylaxis (desensitization)
- Not yet approved by FDA or EMA; investigational use only
Reported positives
- Hormonal optimization benefits in clinical settings
- Potential fertility applications explored
- Short-acting profile allows controlled use
- Research expanding into metabolic applications
Reported negatives
- Very limited community experience outside clinical settings
- Effects not well characterized for self-administration
- Short half-life requires frequent administration
- Limited availability from research suppliers
“Primarily discussed in fertility and hormone optimization contexts. Limited self-experimentation community.”
Self-reported, unverified accounts — not clinical evidence and no substitute for the cited research. Anecdotes are prone to selection bias and placebo effects.
| NCT ID | Title | Peptide | Phase | Status | Completion |
|---|---|---|---|---|---|
| NCT07224490 | Kisspeptin to Quantify GnRH Neuronal Function in Health and Disease Reproductive Disorder, Neurodegeneration +2 more | Kisspeptin | Phase 1 | Recruiting | May 2030 |
| NCT07224438 | Kisspeptin Administration Subcutaneously to Patients With Hypothalamic Amenorrhea Hypothalamic Amenorrhea, Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Recruiting | May 2030 |
| NCT05901467 | Recall by Genotype: Neuropeptide Stimulation Reproductive Disorder | Kisspeptin | Phase 1 | Terminated | May 2024 |
| NCT05971849 | Dampening the Reproductive Axis With Continuous Kisspeptin Reproductive Disorder, PCOS +1 more | Kisspeptin | Phase 1 | Completed | Apr 2024 |
| NCT05896293 | Kisspeptin Administration Subcutaneously to Patients With IHH Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Recruiting | May 2028 |
| NCT05633966 | Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders Hypothalamic Amenorrhea, Hypogonadotropic Hypogonadism | Kisspeptin | Phase 1 | Completed | Aug 2025 |
| NCT05456854 | Evaluation of Kisspeptin Stimulated Insulin Secretion With Hyperglycemic Clamp Metabolic Disease | Kisspeptin | Phase 1 | Withdrawn | Aug 2024 |
| NCT04958109 | Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Oral Glucose Tolerance Test Metabolic Diseases | Kisspeptin | Phase 1 | Completed | Oct 2022 |
| NCT04532801 | Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Physiologic Mixed Meal Tolerance Insulin, Glucose +3 more | Kisspeptin | Phase 1 | Withdrawn | Aug 2024 |
| NCT04648969 | Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Completed | Aug 2025 |
| NCT02956447 | Administration of Kisspeptin in Patients With Hyperprolactinemia Hyperprolactinemia, Hypogonadism | Kisspeptin | Phase 2 | Completed | Jun 2023 |
| NCT02381288 | Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone Low Testosterone | Kisspeptin | Phase 2 | Terminated | Apr 2016 |
| NCT02369796 | A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Terminated | Oct 2015 |
| NCT03315325 | Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men Sterility, Reproductive | Kisspeptin | Phase 3 | Completed | Aug 2014 |
| NCT03286517 | Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys. Reproductive Physiological Phenomena | Kisspeptin | Phase 3 | Completed | Aug 2014 |
| NCT01952782 | Neuropeptides in Human Reproduction Hypogonadotropic Hypogonadism | Kisspeptin | Phase 1 | Completed | May 2016 |
| NCT02081924 | Reproductive Hormones During Sustained Administration of Kisspeptin Fertility Disorders, Hypothalamic Dysfunction | Kisspeptin | Phase N/A | Recruiting | Nov 2027 |
| NCT02877992 | Tachykinin and Kisspeptin Expression in Human Granulosa and Cumulus Cells Infertility | Kisspeptin | Phase N/A | Completed | Jul 2019 |
| NCT03771326 | KP-10 and Insulin Secretion in Men Kisspeptin Action on Insulin in Healthy Normal Men, Kisspeptin Action on Insulin in Obese Diabetic Men | Kisspeptin | Phase 3 | Completed | Nov 2013 |
| NCT01438034 | Kisspeptin in the Evaluation of Delayed Puberty Delayed Puberty, Kallmann Syndrome +2 more | Kisspeptin | Phase 1 | Completed | Sep 2019 |
| NCT01667406 | The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment Infertility | Kisspeptin | Phase 2 | Completed | Oct 2016 |
| NCT01438073 | Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling Hypogonadotropic Hypogonadism, Healthy Postmenopausal Women +1 more | Kisspeptin | Phase 1 | Completed | Apr 2016 |
| NCT01132404 | Study in Men With Prostate Cancer to Assess the Safety, Pharmacokinetics and Testosterone-Lowering Efficacy of TAK-448 Prostate Cancer, Prostatic Neoplasms | Kisspeptin | Phase 1/2 | Terminated | Sep 2011 |
| NCT00914823 | Kisspeptin Administration in the Adult Hypogonadotropic Hypogonadism, Kallmann Syndrome +4 more | Kisspeptin | Phase 1 | Completed | Oct 2021 |
Kisspeptin to Quantify GnRH Neuronal Function in Health and Disease
Kisspeptin Administration Subcutaneously to Patients With Hypothalamic Amenorrhea
Recall by Genotype: Neuropeptide Stimulation
Dampening the Reproductive Axis With Continuous Kisspeptin
Kisspeptin Administration Subcutaneously to Patients With IHH
Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders
Evaluation of Kisspeptin Stimulated Insulin Secretion With Hyperglycemic Clamp
Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Oral Glucose Tolerance Test
Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Physiologic Mixed Meal Tolerance
Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism
Administration of Kisspeptin in Patients With Hyperprolactinemia
Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone
A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism
Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men
Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys.
Reproductive Hormones During Sustained Administration of Kisspeptin
Tachykinin and Kisspeptin Expression in Human Granulosa and Cumulus Cells
Kisspeptin in the Evaluation of Delayed Puberty
The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment
Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling
Study in Men With Prostate Cancer to Assess the Safety, Pharmacokinetics and Testosterone-Lowering Efficacy of TAK-448
Single injection of kisspeptin-54 produces LH surge within 4-12 hours. Unlike hCG, the LH elevation is short-lived (hours rather than days), which eliminates OHSS risk in IVF applications.
PMID:28854728During continuous infusion, LH pulsatility is restored within hours. In hypothalamic amenorrhea studies, 8-hour infusions produced sustained gonadotropin responses.
PMID:24517142Effects are transient - kisspeptin's short half-life means hormonal effects normalize quickly after cessation. This is therapeutically advantageous for IVF safety but may limit other applications.
Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (6 indicators)
Warning Signs (4 indicators)
Bad Signs (5 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Gonadorelin
SynergisticKisspeptin activates GnRH neurons upstream. Both stimulate the HPG axis but at different levels. Combined use may amplify gonadotropin release.
Clomiphene
CompatibleDifferent mechanisms for stimulating HPG axis - clomiphene blocks estrogen feedback, kisspeptin directly activates GnRH. May have additive effects on LH release.
Sermorelin
CompatibleDifferent hormonal axes - kisspeptin targets reproductive axis, sermorelin targets GH axis. No known interactions.
PT-141
CompatibleBoth affect sexual function but through different mechanisms - kisspeptin via limbic brain activity and hormones, PT-141 via melanocortin receptors.
Hcg
CautionBoth used for ovulation triggering in IVF. Kisspeptin produces shorter LH surge (safer for OHSS), while hCG produces prolonged stimulation. Combining may negate kisspeptin's safety advantage.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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