Kisspeptin
KISS1 receptor (GPR54) agonist, natural neuropeptide
Status
In clinical trials
Not approved anywhere; kisspeptin-54 and kisspeptin-10 are used in registered academic trials, while FDA keeps kisspeptin-10 in 503A Category 2 (significant safety risks) after its compounding advisory committee voted 11-0 in October 2024 against allowing it in compounding.
Evidence
Preliminary
Evidence comes from small human studies (typically 6 to 60 participants) of hormone responses, IVF outcomes and brain imaging, with no large randomized trials.
In sport
WADAProhibited (WADA)
Kisspeptin is a natural brain hormone that switches on the reproductive system by triggering release of gonadotrophin-releasing hormone. Synthetic kisspeptin-54 and kisspeptin-10 are being studied to trigger egg maturation in IVF and to treat low sexual desire, but neither is approved.
Structure
54 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
Sequence as text
Kisspeptin-54: H-G-T-S-L-S-P-P-P-E-S-S-G-S-P-Q-Q-P-G-L-S-A-P-H-S-R-Q-I-P-A-P-Q-G-A-V-L-V-Q-R-E-K-D-L-P-N-Y-N-W-N-S-F-G-L-R-F-NH2 Kisspeptin-10: H-Y-N-W-N-S-F-G-L-R-F-NH2
What it is used for
- Triggering egg maturation in IVF, especially in women at high risk of ovarian hyperstimulation syndrome (studied)
- Low sexual desire (hypoactive sexual desire disorder) in men and women (studied)
- Stimulating LH and testosterone release in men (studied)
- Treating low testosterone (secondary hypogonadism) with compounded kisspeptin-10 (claimed, unproven)
How it works
Kisspeptin binds the KISS1 receptor (also called GPR54) on hypothalamic neurons that make gonadotrophin-releasing hormone (GnRH). This releases GnRH, which drives the pituitary to secrete LH and FSH, the hormones that control ovulation, sperm production and sex hormone production. People born with inactivating mutations in the receptor do not go through puberty normally, showing its central role. Brain imaging studies suggest kisspeptin also modulates sexual and emotional processing in limbic brain areas.
How strong the evidence is
Preliminary
In 53 women undergoing IVF, a single kisspeptin-54 injection triggered egg maturation, with a 23% clinical pregnancy rate (Jayasena 2014). In 60 women at high risk of ovarian hyperstimulation syndrome, egg maturation occurred in 95% and none developed moderate or severe hyperstimulation (Abbara 2015). In men, kisspeptin-10 potently raised LH and testosterone (George 2011). Randomized crossover studies completed by 32 women and 32 men with low sexual desire found kisspeptin altered sexual brain processing on MRI and, in men, increased penile tumescence (Thurston 2022; Mills 2023). FDA found insufficient safety data for compounded kisspeptin-10.
Risks and side effects
- Long-term safety unknown; human studies were short and small
- Continuous exposure can blunt the response (tachyphylaxis) in nonclinical studies
- Immunogenicity and impurity concerns flagged by FDA for compounded kisspeptin-10
- Research-chemical products are unregulated and of uncertain purity
- Prohibited for male athletes at all times (WADA S2)
Regulatory status
Status by country
| Jurisdiction | Status | Source |
|---|---|---|
| USUnited States | No authorised medicine | Source 11 |
| EUEuropean Union | No authorised medicine | Source 15 |
| UKUnited Kingdom | No authorised medicine | Source 16 |
| AUAustralia | No authorised medicine | Source 17 |
| CACanada | No authorised medicine | Source 18 |
Sources
- 01Metastasis-suppressor KiSS-1 (kisspeptin precursor) (Q15726)(opens the source in a new tab)
- 02Kisspeptin-10 (CID 25240297)(opens the source in a new tab)
- 03The GPR54 gene as a regulator of puberty(opens the source in a new tab)
- 04Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males(opens the source in a new tab)
- 05Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization(opens the source in a new tab)
- 06Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS) during IVF therapy(opens the source in a new tab)
- 07Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men(opens the source in a new tab)
- 08Kisspeptin modulates sexual and emotional brain processing in humans(opens the source in a new tab)
- 09Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial(opens the source in a new tab)
- 10Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial(opens the source in a new tab)
- 11FDA Briefing Document: kisspeptin-10, Pharmacy Compounding Advisory Committee, October 29, 2024(opens the source in a new tab)
- 12Pharmacy Compounding Advisory Committee meeting, October 29, 2024: minutes(opens the source in a new tab)
- 13Safety Risks Associated with Certain Bulk Drug Substances Nominated for Use in Compounding (Category 2)(opens the source in a new tab)
- 14World Anti-Doping Code International Standard: Prohibited List 2026(opens the source in a new tab)
- 15Find medicine: centrally authorised medicines(opens the source in a new tab)
- 16MHRA Products: active substances beginning with K(opens the source in a new tab)
- 17Australian Register of Therapeutic Goods (ARTG)(opens the source in a new tab)
- 18Unauthorized injectable peptide drugs seized and sold by Canada Peptide may pose serious health risks(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.