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Kisspeptin

Reproductive peptide regulating gonadotropin release and fertility

Overview

Kisspeptin is a family of neuropeptides encoded by the KISS1 gene that serve as critical regulators of the hypothalamic-pituitary-gonadal axis and reproductive function. Acting through the kisspeptin receptor (KISS1R/GPR54), these peptides stimulate gonadotropin-releasing hormone (GnRH) neurons to initiate pulsatile GnRH secretion, thereby controlling downstream release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Research demonstrates kisspeptin is essential for puberty onset, maintaining fertility, and normal reproductive cycling. Mutations in KISS1 or KISS1R cause hypogonadotropic hypogonadism and failure of puberty. Clinical studies have explored kisspeptin for fertility treatment, showing it can induce ovulation and restore gonadotropin pulsatility. The peptide may offer advantages over GnRH analogs in assisted reproduction with reduced risk of ovarian hyperstimulation syndrome. Research continues into kisspeptin's roles in metabolic regulation, pregnancy maintenance, and cancer metastasis suppression. The kisspeptin system represents a key control point for reproductive neuroendocrinology.

Last reviewed: 2026-08-18

Identity & Aliases

Also known as

Kisspeptin-54KP-54MetastinKisspeptin-10KP-10KISS1 peptideKisspeptin-13

Status: Research compound - Reproductive hormone modulator

CAS374675-21-5

PubChem25077993

Full composition (formula, molecular weight, sequence) in Quick Facts →

Research Areas

Fertility / IVF triggerOvarian hyperstimulation syndrome preventionHypothalamic amenorrheaPuberty regulationReproductive neuroendocrinology

Available Evidence

Human

Clinical studies at Imperial College London showed a single subcutaneous kisspeptin-54 injection can trigger oocyte maturation in women undergoing IVF (mature eggs retrieved, fertilization in 92% of patients, clinical pregnancy rate 23%). In a phase 2 randomized trial of 60 women at high risk of OHSS, kisspeptin-54 triggered oocyte maturation in 95% with no moderate/severe/critical OHSS and live-birth rates up to 45-62% per transfer. Twice-weekly kisspeptin-54 for 8 weeks stimulated reproductive hormone release in women with hypothalamic amenorrhea. Intranasal kisspeptin administration was shown (2025) to rapidly stimulate gonadotropin release in humans.

Animal

Kisspeptin signaling (KISS1/KISS1R) is established as essential for puberty onset and the GnRH/LH surge driving ovulation; knockout models are infertile and lack pubertal development.

In Vitro

Kisspeptin activates KISS1R (GPR54) on GnRH neurons; mutations in KISS1 or KISS1R cause hypogonadotropic hypogonadism in humans.

Uncertain

Tachyphylaxis limits repeated dosing (twice-daily dosing caused desensitization). Larger phase 3 programs and approval are pending; use for libido enhancement or TRT support is not clinically validated.

Key Studies & Findings

4 studies

Clinical2014

A single SC injection of kisspeptin-54 triggered oocyte maturation in 53 women undergoing IVF; fertilization occurred in 92% of patients with biochemical and clinical pregnancy rates of 40% and 23%.

Clinical trial (J Clin Invest)

Clinical2015

In 60 women at high risk of OHSS during IVF, kisspeptin-54 triggered oocyte maturation in 95%, produced live-birth rates of 45-62% per transfer, and no woman developed moderate, severe, or critical OHSS.

Phase 2 randomized clinical trial (J Clin Endocrinol Metab)

Clinical2010

Twice-weekly kisspeptin-54 for 8 weeks significantly elevated reproductive hormone levels vs saline in women with hypothalamic amenorrhea, with only partial desensitization (versus complete tolerance with twice-daily dosing).

Randomized controlled study (Clin Pharmacol Ther)

Clinical2025

Intranasal kisspeptin rapidly stimulated gonadotropin release in humans, suggesting a non-invasive route for clinical use.

Human physiology study (EBioMedicine)

Benefits & Effects

6 documented

GnRH stimulation

anecdotal

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Fertility enhancement

anecdotal

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Libido support

anecdotal

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Reproductive health

anecdotal

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Testosterone optimization

anecdotal

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Natural hormone regulation

anecdotal

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Side Effects & Safety

4 reported

Generally well-tolerated

MildUncommon

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Headache

MildUncommon

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Mild nausea

MildUncommon

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Limited long-term data

MildUncommon

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Limitations & Open Questions

All human data come from a single research group's small trials; no approved product exists. Repeated dosing causes tachyphylaxis, and dosing regimens are not standardized. Effects in men and for libido remain speculative.

Pharmacology

Kisspeptin is the product of the KISS1 gene; kisspeptin-54 is the major circulating isoform. It activates KISS1R (GPR54) on GnRH neurons, stimulating GnRH and downstream LH/FSH release. In trials, SC kisspeptin-54 was dosed 1.6-12.8 nmol/kg as a single trigger injection; plasma half-life is short (kisspeptin-10 much shorter than kisspeptin-54), and repeated frequent dosing causes receptor desensitization.

Reported Research Dosing

Reported values from research literature and community protocols. Educational reference only — not a dosing recommendation or medical advice.

100-200mcg

Route: IV/SC

Half-life: 4 minutes

Research Protocols

Gonadotropin stimulation

Dose: 100-200mcg
Frequency: Single dose or 2-3x/week
Route: SubQ

Fertility support

Dose: 0.4-1.0 nmol/kg (50-150mcg)
Frequency: As directed by physician
Route: SubQ (KP-54)

Sexual function

Dose: 1 nmol/kg/h
Frequency: 75 min IV infusion (clinical)
Route: IV infusion

Research protocols

Dose: 0.3-10 nmol/kg
Frequency: Variable by protocol
Route: IV bolus or SubQ

Research protocols are for educational purposes only. Always consult qualified medical professionals.

Frequently Asked Questions

What does kisspeptin do?

It is a neuropeptide that activates KISS1R on GnRH neurons, driving GnRH and LH/FSH secretion — a master regulator of puberty and fertility.

Has kisspeptin been used in IVF?

Yes — in clinical trials, kisspeptin-54 has been used to trigger oocyte maturation in IVF, including in women at high risk of ovarian hyperstimulation syndrome, where it avoided OHSS.

Is kisspeptin approved as a drug?

No. Kisspeptin remains an investigational peptide; no regulatory approval has been granted.

Does repeated kisspeptin stop working?

Frequent dosing (e.g., twice daily) produces tachyphylaxis/desensitization; less frequent regimens such as twice-weekly dosing only partially desensitize.