Kisspeptin
Reproductive Hormone Peptide
aka Kisspeptin-54 · Kisspeptin-10 · metastin · KISS1 · KP-54 · KP-10 · intranasal kisspeptin
Research describes kisspeptin as a master hypothalamic regulator that triggers the reproductive hormone cascade via GnRH.
Sequence
YNWNSFGLRF
Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2
Mechanism of action
Kisspeptin binds to the GPR54 receptor on neurons in the hypothalamus, stimulating the release of gonadotropin-releasing hormone (GnRH). This action triggers the pituitary gland to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are crucial for reproductive function. Kisspeptin also influences the production of sex hormones like testosterone and estradiol.
What the evidence actually shows
Grade A: Multiple RCTs including 2025 double-blind crossover placebo-controlled trial (eBioMedicine/Lancet). Intranasal route demonstrated effective, non-invasive delivery via novel olfactory GnRH pathway. Works in healthy men, women, and hypothalamic amenorrhoea patients. PMID: 40215751.
Regulatory status
In the UK, kisspeptin is considered a research compound and is not approved for general medical use by the MHRA.
Source ↗Pharmacokinetics
Dosing — what backs each figure
Kisspeptin has substantial and well-documented human trial dosing, chiefly kisspeptin-54 at 9.6 nmol/kg subcutaneously as a single IVF trigger and kisspeptin-10 as subcutaneous infusions of 1.25-10 nmol/kg/h (or 150-180 nmol/h for 5-12 days). All of it is weight- or infusion-rate-based investigational dosing; kisspeptin is not approved and there is no established self-administered regimen.
Single subcutaneous injection of kisspeptin-54 9.6 nmol/kg given 36 hours prior to oocyte retrieval, with randomisation to a second identical dose or saline 10 hours later; the second dose improved the proportion of patients achieving >=60% oocyte yield (71% vs 45%)
62 women aged 18-34 at high risk of ovarian hyperstimulation syndrome undergoing IVF (phase 2 randomised controlled trial) · subcutaneous
Three linked studies: (1) acute 8-hour subcutaneous kisspeptin-10 dose-response infusions at 1.25-10.0 nmol/kg/h; (2) continuous subcutaneous infusion at 180 nmol/h for 5 days; (3) daily intermittent 8-hour-on / 16-hour-off subcutaneous infusions at 150 nmol/h for 12 days. Plus a 1 nmol/kg kisspeptin-10 bolus to confirm receptor responsiveness at day 12
15 healthy men (study 1 n=7, study 2 n=4, study 3 n=7) plus 12 controls · subcutaneous infusion
- Dose
- Research literature cites microgram-range boluses/infusions
- Frequency
- 2-3x weekly
Why this isn't evidence
Human kisspeptin dosing is weight- or rate-based in nanomoles (9.6 nmol/kg subcutaneous single trigger dose, or 1.25-10 nmol/kg/h and 150-180 nmol/h infusions) delivered as one-off triggers or continuous/intermittent infusions, so the vague 'microgram-range' descriptor combined with a '2-3x weekly' schedule and the luteal-phase claim in dosingNotes match no published regimen.
This figure is shown because it is what circulates and what people search for — not because it is supported. Cycle lengths in particular tend to be convention copied between compounds rather than anything derived from a compound's own pharmacokinetics.
Handling and storage
Safety
- ·Nausea
- ·Headache
- ·Flushing
- ·Severe allergic reactions
- ·Ovarian hyperstimulation syndrome
- ·Pregnancy
- ·Breastfeeding
- ·"Known hypersensitivity to kisspeptin"
- ·GnRH analogs may alter the effects of kisspeptin by modifying baseline hormone levels
Generally well tolerated in studies
Reported combinations
- ·L-arginine, which may enhance nitric oxide production and improve reproductive outcomes
- ·GnRH antagonists, which may counteract the effects of kisspeptin
Combination claims in this dataset are largely unsourced and should be treated as folk knowledge until a citation appears beside them.
References (3)
- Abbara A, Jayasena CN, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Nijher GM, Comninos AN, Peters D, Buckley A, Ratnasabapathy R, Prague JK, Salim R, Lavery SA, Bloom SR, Szigeti M, Ashby DA, Trew GH, Dhillo WS (2015) Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy ↗The Journal of Clinical Endocrinology and MetabolismPMID 26192876DOI
Phase 2 open-label randomised trial in 60 women at high risk of OHSS at Hammersmith Hospital: a single injection of kisspeptin-54 at 3.2, 6.4, 9.6 or 12.8 nmol/kg was used to trigger oocyte maturation, with retrieval 36 h later.
- Abbara A, Clarke S, Islam R, Prague JK, Comninos AN, Narayanaswamy S, Papadopoulou D, Roberts R, Izzi-Engbeaya C, Ratnasabapathy R, Nesbitt A, Vimalesvaran S, Salim R, Lavery SA, Bloom SR, Huson L, Trew GH, Dhillo WS (2017) A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial ↗Human ReproductionPMID 28854728DOI
Phase 2 randomised placebo-controlled trial in 62 women at high risk of OHSS: a second dose of kisspeptin-54 given 10 h after the first improved oocyte yield; a single dose produces an LH surge of about 12-14 h.
- Navarro VM (2020) Metabolic regulation of kisspeptin - the link between energy balance and reproduction ↗Nature Reviews EndocrinologyPMID 32427949DOI
Review of kisspeptin/KISS1R signalling as the gatekeeper of GnRH release and its regulation by metabolic status.
Data provenance
Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.
Could not verify
storage.lyophilized, storage.reconstituted, storage.lightSensitive, reconstitution.solvent