Kisspeptin-10

The Kisspeptin-10 evidence base cited here is 7 sources — 3 clinical, 3 review. Its strongest evidence is human — 3 clinical studies, most recently 2014 ("Increasing LH Pulsatility in Women with Hypothalamic Amenorrhoea Using I…"). Regulatory status: Not FDA-approved (research).

• Kisspeptin is a family of neuropeptides (from the KISS1 gene) that act as the master switch of the reproductive axis — they potently drive the GnRH neurons that control puberty, fertility, and sex-hormone production.
• Unusually for a research peptide, it has genuinely STRONG human RCT data: trials in low sexual desire (men and women) and an IVF ovulation trigger with a reported ~45% live-birth rate and zero severe ovarian hyperstimulation (OHSS) — a potentially safer alternative to HCG in high-risk patients.
• The two common forms are Kisspeptin-10 (~1,213 Da) and the longer Kisspeptin-54 (~6,087 Da); both are C-terminally amidated fragments of a 145-aa precursor.

Kisspeptin sits at the very top of the reproductive hormone cascade. By stimulating hypothalamic GnRH neurons, it sets off the chain that releases LH and FSH from the pituitary and, in turn, testosterone or estrogen from the gonads. That makes it a research tool for infertility, low libido, and reproductive disorders — and, notably, one of the better-evidenced compounds in this library.

It is investigational and not FDA-approved; everything below is research/clinical context, not medical guidance.

Kisspeptins are RFamide neuropeptides cleaved from a 145-amino-acid KISS1 precursor and C-terminally amidated. The two forms used in research are Kisspeptin-10 (a 10-residue C-terminal fragment, ~1,213 Da, sequence Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂) and Kisspeptin-54 (a 54-residue fragment, ~6,087 Da). KP-54 is longer-acting; KP-10 is shorter and faster.

Both signal through the same receptor (GPR54 / KISS1R) on GnRH neurons — the difference is duration and the clinical context they've been studied in.

Kisspeptin binds GPR54/KISS1R receptors on hypothalamic GnRH neurons, triggering pulsatile GnRH release. That GnRH drives the pituitary to secrete LH and FSH, which then stimulate the gonads to produce sex steroids and support gamete maturation. Because it acts one step upstream of GnRH, kisspeptin can 'wake up' a dormant-but-intact reproductive axis — which is the basis for its use in hypogonadotropic hypogonadism and hypothalamic amenorrhea. Its pulsatile nature is essential: continuous exposure desensitizes the system.

• Time to peak: ~3 minutes (KP-10 is very fast)
• Half-life: ~28 minutes (KP-10); KP-54 is longer-acting
• Largely cleared within ~2.3 hours (Dhillo et al.)

There is no approved dosing. Figures below are from clinical/research protocols, included for context only — and the no-daily-dosing rule is the key one.

• Gonadotropin stimulation: ~100–200 mcg single dose, or 2–3× per week (subcutaneous)
• Fertility (KP-54): ~0.4–1.0 nmol/kg as directed, coordinated with the menstrual cycle
• Sexual-function research: ~1 nmol/kg/h as a 75-minute IV infusion (clinical setting)
• Avoid daily dosing — 2–3× per week is the practical ceiling to prevent receptor desensitization

The single most important practical fact: do NOT dose kisspeptin daily. Continuous receptor stimulation causes tachyphylaxis (the response fades), which is the opposite of the goal.

• Reconstitute with bacteriostatic water down the vial wall; swirl gently, never shake; solution should be clear.
• Photosensitive — use light-protective (amber/opaque) packaging and minimize light exposure.
• Refrigerate at 2–8°C; use KP-10 within ~7 days and KP-54 within ~14 days; discard if yellowed or cloudy.

Generally well-tolerated in trials. The key safety/usage points: avoid daily administration (tachyphylaxis), use caution with cardiovascular disease (possible vasoconstrictive effects), and monitor for ovarian hyperstimulation in women undergoing fertility protocols (though kisspeptin's OHSS risk appears LOWER than HCG's, which is part of its appeal). Not recommended in pregnancy/breastfeeding; fertility use should be supervised by a reproductive endocrinologist.

• Intranasal kisspeptin (2025, human): KP-54 rapidly stimulated gonadotropin release without side effects in healthy adults and hypothalamic-amenorrhea patients; a stable 60-day formulation was reported.
• HSDD in men (2023 RCT, 32 men): IV kisspeptin increased penile tumescence up to ~56% vs placebo and modulated sexual-processing brain networks.
• HSDD in women (2022 RCT, 32 women): modulated sexual/attraction brain processing and increased self-reported arousal vs placebo.
• IVF triggering (KP-54): used as an ovulation trigger with a reported ~45% live-birth rate and zero severe OHSS — a potentially safer alternative to HCG in high-OHSS-risk patients.

Kisspeptin is investigational and not FDA-approved. It is sold as a research chemical for laboratory use only, not intended for human consumption, despite an unusually strong (for this space) human-trial record.

All citations link to the original source (PubMed, journal site, or regulatory filing). Independent research database — no vendor influence on what's cited.