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Hormonal — GnRH RegulatorResearch Use

Kisspeptin

Also known as: Kisspeptin-10 · Kisspeptin-54 · Metastin

MW

1302.45 Da

Amino Acids

10 AA

Half-Life

28 minutes

Route

SubQ, IV

CAS

374675-21-5

Formula

C63H83N13O14

Amino Acid Sequence

YNWNSFGLRF-NH2

Mechanism of Action

Kisspeptin is a hypothalamic neuropeptide encoded by the KISS1 gene that serves as the master regulator of the reproductive axis. Kisspeptin-10 (the 10-amino acid C-terminal active fragment) is the clinically used form.

PRIMARY MECHANISM — KISS1R/GPR54 ACTIVATION: Binds KISS1R (GPR54) on hypothalamic GnRH neurons → triggers pulsatile GnRH (gonadotropin-releasing hormone) release → LH and FSH secretion from anterior pituitary → gonadal steroid production (testosterone in men, estrogen/progesterone in women).

MASTER REGULATOR: Kisspeptin neurons integrate metabolic (leptin), circadian, and stress signals to control reproductive function. Loss-of-function KISS1R mutations cause hypogonadotropic hypogonadism — demonstrating kisspeptin's essential role.

CLINICAL APPLICATIONS: Being investigated as (1) fertility treatment to trigger ovulation, (2) diagnostic tool for pubertal disorders, (3) means to restart suppressed HPG axis (e.g., after anabolic steroid use).

Unlike GnRH analogs (leuprolide, buserelin) which cause desensitization with continuous use, kisspeptin may produce more physiologic pulsatile GnRH release.

Dosing Protocol

Low Dose

███ – ███ mcg/day

Standard Dose

███ mcg/day

High Dose

███ – ███ mcg/day

Dosing protocols are for paid members

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Frequency

Single or repeated boluses in clinical research setting.

Half-Life

28 minutes

Reconstitution Guide

Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.

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Clinical Warnings

Rapid LH surge — requires clinical monitoring.

Not for self-administration.

May trigger ovarian hyperstimulation in women.

Not FDA approved for clinical use yet.

HPG axis disruption if misused.

Contraindications

Absolute

Pregnancy

Hormone-sensitive cancers

Relative Cautions

PCOS

Hypothalamic amenorrhea

Hypogonadism

Side Effect Profile

Mild

  • Flushing
  • Headache
  • Mild nausea

Moderate

  • Abdominal discomfort
  • Hot flashes

Severe (Rare)

  • Ovarian hyperstimulation (in IVF)

Synergistic Peptides

PT-141Melanotan II

Common Stacks

PT-141

Research Status

ACTIVE CLINICAL DEVELOPMENT. PMID 26040266 (Jayasena 2014): Pulsatile LH stimulation in men and women. PMID 33811296 (Abbara 2021): Fertility outcomes. Multiple ongoing clinical trials for reproductive medicine.

Frequently Asked Questions

How does Kisspeptin work?

Kisspeptin is a hypothalamic neuropeptide encoded by the KISS1 gene that serves as the master regulator of the reproductive axis. Kisspeptin-10 (the 10-amino acid C-terminal active fragment) is the clinically used form. PRIMARY MECHANISM — KISS1R/GPR54 ACTIVATION: Binds KISS1R (GPR54) on hypothalamic GnRH neurons → triggers pulsatile GnRH (gonadotropin-releasing hormone) release → LH and FSH secretion from anterior pituitary → gonadal steroid production (testosterone in men, estrogen/progestero

What is the standard dose of Kisspeptin?

Kisspeptin dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: Single or repeated boluses in clinical research setting.

What is the half-life of Kisspeptin?

The half-life of Kisspeptin is 28 minutes. This determines optimal dosing frequency and timing.

Who should not use Kisspeptin?

Kisspeptin is absolutely contraindicated in: Pregnancy; Hormone-sensitive cancers. Use with caution in: PCOS; Hypothalamic amenorrhea; Hypogonadism.

What are the side effects of Kisspeptin?

Common mild side effects include: Flushing, Headache, Mild nausea. Moderate effects: Abdominal discomfort, Hot flashes.

What peptides stack well with Kisspeptin?

Kisspeptin is commonly stacked with: PT-141, Melanotan II.

How do you reconstitute Kisspeptin?

Kisspeptin is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.

How long should you cycle Kisspeptin?

Kisspeptin cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.

References & Citations

10 PubMed studies · 3 clinical trials

KNDy neurons as an indirect target of insulin-like growth factor-1.

Silva Josiane do N, de Sousa Ligia M M, de Sousa Maria E, Vieira Henrique R et al.. Journal of neuroendocrinology. 2026

PubMed: 41423875DOI ↗C — Research Article

Neurons in the arcuate nucleus of the hypothalamus (ARH) that coexpress kisspeptin, neurokinin B, and dynorphin (KNDy neurons) are considered the gonadotropin-releasing hormone (GnRH) pulse generator

The role of hypothalamic kisspeptin neurons in coordinating reproduction and metabolism.

Rønnekleiv Oline K, Qiu Jian, Kelly Martin J. Journal of neuroendocrinology. 2026

PubMed: 41407546DOI ↗C — Research Article

The hypothalamic control of fertility is a quintessential homeostatic function. Given that reproduction is metabolically demanding, coordination between energy status and reproductive function is esse

Haploinsufficiency of Sox2 causes fewer GnRH neurons and delayed puberty in mice.

Cassin Jessica, Dunn Geneva A, Nguyen Ryan D, Chen Vivian et al.. Endocrinology. 2026

PubMed: 41403157DOI ↗C — Research Article

Mutations in the SOX2 gene have been previously linked to a syndromic form of isolated hypogonadotropic hypogonadism, with additional ocular and neurodevelopmental phenotypes. Recently, we reported a

The hypothalamic effects of PACAP on the hypothalamic-pituitary-gonadal axis in male mice.

Faludi Péter, Barabás Klaudia, Lengyel Ferenc, Udvarácz Ildikó et al.. Frontiers in endocrinology. 2025

PubMed: 41347138DOI ↗C — Research Article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal peptide (VIP) neuropeptide family and plays a role in the regulation of several releasing hormones a

Dual rescue mission: P-G3 dendrimer addresses ovarian and neuroendocrine roots of obesity-linked subfertility.

Nie Yunhan, Kuang Zhe, Si Jiqiang, Huang Yuting et al.. Journal of advanced research. 2025

PubMed: 41274638DOI ↗C — Research Article

The dual pathology of obesity-induced infertility, which encompasses both peripheral (ovarian) and central (hypothalamic-pituitary) mechanisms, is well documented. However, existing therapeutic approa

Acupuncture and the HPO Axis: A Review of Neuroendocrine Mechanisms With Implications for Ovarian Function.

Bu Yu, Yan Jinglan, Zhang Zhen, Xue Song et al.. Journal of integrative neuroscience. 2025

PubMed: 41200977DOI ↗C — Research Article

Declining fertility due to ovarian dysfunction is a critical concern for population sustainability. Acupuncture shows potential for ovarian functional restoration, primarily mediated through its neuro

Molecular pathways affecting reproductive efficiency in seasonal breeders: prospects and implications for improving fertility in donkeys.

Akhtar Muhammad Faheem, Ali Shahzad, Hassan Faizul, Changfa Wang. Frontiers in veterinary science. 2025

PubMed: 41169682DOI ↗C — Research Article

Intense neuroendocrine and molecular pathways with environmental sensitivity maintain reproductive efficiency in seasonal breeders, together with donkeys. The hypothalamic-pituitary-gonadal (HPG) axis

Neuronal plasticity at puberty in mouse hypothalamic Kiss1 neurons that control fertility.

Zhang Yuanxin, Pakulat Leonie M, Takács Szabolcs, Campbell Lauren et al.. Proceedings of the National Academy of Sciences of the United States of America. 2025

PubMed: 41118223DOI ↗A — High-Impact Journal

Puberty is a critical transition period to achieve reproductive capacity in all mammalian species. At puberty, hypothalamic Kiss1 neurons release kisspeptin, stimulating gonadotropin-releasing hormone

Registered Clinical Trials

Molecules Associated with Pediatric Obesity

The Impact of Time-restricted Eating on the Outcomes Associated With Polycystic Ovary Syndrome

Detection of Kisspeptins and miRNAs in Patients With Non-viable Pregnancy

Symptom Indications

Low libidoInfertilityHypothalamic amenorrheaHypogonadism

Full Clinical Access

Complete Kisspeptin Protocol

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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.