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%
- Human research
- 75%
Based on 24 cited sources
Numeric assessment unreviewed
A historical numeric score is recorded but has not passed a current, compound-specific assessment review. No numeric score is displayed.
This is a limitation of the numeric assessment, not a measured absence of benefit. It does not re-review the separately recorded catalogue classification or establish efficacy or safety.
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 (date type unverified) |
| NCT07224438 | Kisspeptin Administration Subcutaneously to Patients With Hypothalamic Amenorrhea Hypothalamic Amenorrhea, Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Recruiting | May 2030 (date type unverified) |
| NCT05901467 | Recall by Genotype: Neuropeptide Stimulation Reproductive Disorder | Kisspeptin | Phase 1 | Terminated | May 2024 (date type unverified) |
| NCT05971849 | Dampening the Reproductive Axis With Continuous Kisspeptin Reproductive Disorder, PCOS +1 more | Kisspeptin | Phase 1 | Completed | Apr 2024 (date type unverified) |
| NCT05896293 | Kisspeptin Administration Subcutaneously to Patients With IHH Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Recruiting | May 2028 (date type unverified) |
| NCT05633966 | Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders Hypothalamic Amenorrhea, Hypogonadotropic Hypogonadism | Kisspeptin | Phase 1 | Completed | Aug 2025 (date type unverified) |
| NCT05456854 | Evaluation of Kisspeptin Stimulated Insulin Secretion With Hyperglycemic Clamp Metabolic Disease | Kisspeptin | Phase 1 | Withdrawn | Aug 2024 (date type unverified) |
| NCT04958109 | Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Oral Glucose Tolerance Test Metabolic Diseases | Kisspeptin | Phase 1 | Completed | Oct 2022 (date type unverified) |
| NCT04532801 | Evaluation of Kisspeptin Glucose-Stimulated Insulin Secretion With Physiologic Mixed Meal Tolerance Insulin, Glucose +3 more | Kisspeptin | Phase 1 | Withdrawn | Aug 2024 (date type unverified) |
| NCT04648969 | Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Completed | Aug 2025 (date type unverified) |
| NCT02956447 | Administration of Kisspeptin in Patients With Hyperprolactinemia Hyperprolactinemia, Hypogonadism | Kisspeptin | Phase 2 | Completed | Jun 2023 (date type unverified) |
| NCT02381288 | Effects of TAK-448 in Middle-aged and Older Men With Low Testosterone Low Testosterone | Kisspeptin | Phase 2 | Terminated | Apr 2016 (date type unverified) |
| NCT02369796 | A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism Hypogonadotropic Hypogonadism | Kisspeptin | Phase 2 | Terminated | Oct 2015 (date type unverified) |
| NCT03315325 | Age-dependent Changes in the Responsiveness of Hypothalamic Pituitary Gonadal Axis in Men Sterility, Reproductive | Kisspeptin | Phase 3 | Completed | Aug 2014 (date type unverified) |
| NCT03286517 | Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys. Reproductive Physiological Phenomena | Kisspeptin | Phase 3 | Completed | Aug 2014 (date type unverified) |
| NCT01952782 | Neuropeptides in Human Reproduction Hypogonadotropic Hypogonadism | Kisspeptin | Phase 1 | Completed | May 2016 (date type unverified) |
| NCT02081924 | Reproductive Hormones During Sustained Administration of Kisspeptin Fertility Disorders, Hypothalamic Dysfunction | Kisspeptin | Phase N/A | Recruiting | Nov 2027 (date type unverified) |
| NCT02877992 | Tachykinin and Kisspeptin Expression in Human Granulosa and Cumulus Cells Infertility | Kisspeptin | Phase N/A | Completed | Jul 2019 (date type unverified) |
| 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 (date type unverified) |
| NCT01438034 | Kisspeptin in the Evaluation of Delayed Puberty Delayed Puberty, Kallmann Syndrome +2 more | Kisspeptin | Phase 1 | Completed | Sep 2019 (date type unverified) |
| NCT01667406 | The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment Infertility | Kisspeptin | Phase 2 | Completed | Oct 2016 (date type unverified) |
| NCT01438073 | Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling Hypogonadotropic Hypogonadism, Healthy Postmenopausal Women +1 more | Kisspeptin | Phase 1 | Completed | Apr 2016 (date type unverified) |
| 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 (date type unverified) |
| NCT00914823 | Kisspeptin Administration in the Adult Hypogonadotropic Hypogonadism, Kallmann Syndrome +4 more | Kisspeptin | Phase 1 | Completed | Oct 2021 (date type unverified) |
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.
Neuropeptides in Human Reproduction
Reproductive Hormones During Sustained Administration of Kisspeptin
Tachykinin and Kisspeptin Expression in Human Granulosa and Cumulus Cells
KP-10 and Insulin Secretion in Men
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
Kisspeptin Administration in the Adult
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.
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
Use the source links in the research discussion above to inspect the referenced records.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength labels summarize the cited material for this entry and should be read alongside its population, model, and study limitations.
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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Compared With
2 comparisonsConditions Studied
3 entries- Kisspeptin for IVF Oocyte Maturation Trigger Kisspeptin-54 has been evaluated as an alternative to hCG for triggering oocyte maturation in IVF. Phase 2 RCTs at Imperial Colleg…
- Kisspeptin for Hypothalamic Amenorrhea Kisspeptin infusion restores pulsatile LH secretion in women with hypothalamic amenorrhea. Studies showed 3-fold increase in LH pu…
- Kisspeptin for Hypoactive Sexual Desire Disorder fMRI studies show kisspeptin enhances limbic brain activity to sexual stimuli in men. RCTs demonstrated enhanced brain responses t…