Kisspeptin-10 (KP-10)
Kisspeptin-10 — the reproductive master-switch peptide: the chocolate name, the cancer origin, and the real trials

Class: peptide
Synonyms: Kisspeptin-10
KP-10
metastin (the parent's original name)
Function tags: reproductive-axis stimulation (GnRH→LH/FSH)
fertility / IVF triggering
sexual desire / arousal (HSDD)
(research tool for reproductive endocrinology)
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-13

In brief: Kisspeptin-10 is the minimal active fragment of kisspeptin — the hypothalamic peptide that sits at the top of the reproductive hormone axis and acts as its master switch. It works upstream: activating KISS1R on GnRH neurons, which drives pulsatile GnRH → LH/FSH → testosterone/estradiol. Its story is unusually rich: the gene was named after Hershey's Kisses chocolate, was discovered in cancer research (as the metastasis suppressor "metastin") before its reproductive role was known, and proved essential when people lacking it were found not to undergo puberty. Crucially — and unlike most compounds here — kisspeptin has real, current clinical science behind it: Imperial College London teams have run trials in hypogonadism, IVF triggering, hypothalamic amenorrhea, and hypoactive sexual desire disorder, where randomized placebo-controlled studies showed it modulates the brain's arousal/"attraction" circuits and reduces sexual aversion. The honest caveats: it's still research-only (not approved), its strongest data are in specific clinical settings (not the bodybuilding "testosterone restart" use it's often sold for), and it has a very short half-life. Bottom line: a genuinely important hormone with real translational momentum — promising and well-studied, but not yet an approved therapy.

## Identity an **endogenous decapeptide** — the **minimal fully-active fragment** of kisspeptin, the hypothalamic peptide that sits at the very **top of the reproductive hormone axis**. The **KISS1** gene (chromosome 1q32) makes a 145-aa precursor, cleaved to **kisspeptin-54 (metastin)** and shorter fragments including **KP-10**, which retains full activity at the **KISS1R (GPR54)** receptor. Unlike hormones that act on the gonads directly, kisspeptin acts **upstream — it "controls the controllers."** ## Mechanism (as proposed) kisspeptin neurons (in the hypothalamic **arcuate** and **AVPV** nuclei) release kisspeptin, which binds **KISS1R (GPR54)** — a **Gq/11-coupled GPCR** — on **GnRH neurons**, activating **phospholipase C → IP3/DAG → calcium** and **ERK1/2/p38** signalling. This makes GnRH neurons fire and release **GnRH in pulses** into the pituitary portal circulation; the pituitary then secretes **LH and FSH**, which drive the gonads to make **testosterone/estradiol**. Kisspeptin is thus the **dominant "gate" for GnRH pulse generation** — the reason it's called the reproductive **master regulator**. It's also **sensitive to sex-steroid feedback and metabolic cues** (linking body energy status to fertility). The separate **arousal/attraction** effects appear to involve **limbic brain activity** and are reported to be **partly independent** of the downstream hormone rise — i.e. kisspeptin may act on **desire circuits directly**, not only via testosterone/estradiol.

Evidence grades by outcome:
outcome: Stimulating the reproductive axis (LH/FSH release)
grade: B
base: Robust, repeatedly demonstrated in humans (IV kisspeptin → rapid LH/FSH rise); genetics confirm necessity
caveat: Well-established physiology in controlled settings; short-acting; response shows sexual dimorphism (differs by sex and menstrual-cycle phase)
outcome: IVF / egg-maturation triggering
grade: B
base: Clinical trials: kisspeptin can trigger oocyte maturation with lower OHSS risk than standard hCG
caveat: Promising, actively developed; not yet a standard/approved trigger
outcome: Hypoactive sexual desire disorder (HSDD) — arousal/attraction
grade: C
base: 2 randomized placebo-controlled trials (JAMA Netw Open 2022/2023, 32 women + 32 men): modulated sexual-processing brain networks, ↑"sexy" ratings, ↓aversion
caveat: Real RCT signal on brain processing + self-report — but early, small, mechanistic endpoints; not an approved HSDD drug
outcome: Idiopathic hypogonadotropic hypogonadism / hypothalamic amenorrhea
grade: C
base: Mechanistic + clinical studies restoring axis activity
caveat: Coherent, promising; still investigational
outcome: "PCT / natural-testosterone restart" (the bodybuilding use)
grade: F
base: Extrapolated from LH/FSH stimulation
caveat: Not clinically established for this purpose; short half-life and pulsatility make casual self-use dubious
outcome: Safety
base: Controlled-setting trials
caveat: Reported well-tolerated with no significant adverse events in trials; but off-protocol self-dosing of an upstream reproductive hormone is unstudied; product quality unverified

Legal status:
region: EU
status: Not FDA-approved (gray-market)
note: research use only; not approved by FDA or EMA for any therapeutic use. But — unlike most gray-market peptides — it has an active, legitimate clinical-trial pipeline (Phase 1/2), so its "unproven" status is "not yet approved, actively being developed," not "fringe."

Cosmetic claims:

Note: The reproductive "master switch" — with real modern clinical science and three great backstories. This is one of the register's stronger entries: a genuine upstream controller of human reproduction, backed by actual randomized trials (Imperial College London), yet still research-only. Three threads of intrigue: (1) it's named after Hershey's Kisses chocolate; (2) it was discovered in cancer research (as a metastasis suppressor) before anyone knew it ran reproduction; (3) recent placebo-controlled trials show it modulates the "attraction" and desire circuits of the brain — a real, published sexual-desire signal, not gray-market folklore.
Status note: active clinical pipeline — watch for Phase 2/3 progress in IVF triggering and HSDD; approval would move several grades

Sources:
Lee JH, Welch DR, et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. (1996) — discovery/naming; Ohtaki et al. 2001 (metastin/KISS1R).
Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update. 2014; Koysombat et al. (Dhillo/Abbara), Physiol Rev. 2025 (current synthesis).
Thurston L, et al. Effects of kisspeptin administration in women with HSDD: a randomized clinical trial. JAMA Netw Open. 2022; Mills EG, et al. …in men with HSDD. JAMA Netw Open. 2023 (the RCT arousal/attraction data).
Comninos AN, et al. — kisspeptin and attraction/olfaction brain processing (JCI Insight, 2020).
Human genetics: KISS1/KISS1R loss-of-function → idiopathic hypogonadotropic hypogonadism. (Research-use-only; not FDA/EMA-approved as of 2026.)