Kisspeptin
low riskAlso: Metastin · KiSS-1 derived peptide
Kisspeptin is an endogenous hypothalamic peptide that serves as the master regulator of GnRH (and therefore reproductive hormone) secretion. It has been extensively studied in human reproductive medicine and has significant diagnostic and potential therapeutic applications.
Reported Benefits
GnRH/LH Stimulation
Consistent LH pulse generation demonstrated in extensive human pharmacology studies.
Reproductive Function Assessment
Used as diagnostic tool to assess HPG axis integrity.
Fertility Treatment
Small trials in anorexia-related infertility and hypothalamic amenorrhea show promise.
Mechanism of Action
Kisspeptin activates GPR54 (KISS1R) receptors on GnRH neurons in the hypothalamus, triggering GnRH pulse release. GnRH then stimulates pituitary LH and FSH secretion, which drives gonadal sex hormone production. Kisspeptin is positioned upstream of GnRH in the reproductive axis and serves as the primary transducer of metabolic, photoperiodic, and gonadal feedback signals into reproductive control.
Key Clinical Studies
Dhillo WS et al. (2005)
pharmacology study · 10 healthy men
Kisspeptin-54 injection triggers robust LH pulse
Jayasena CN et al. (2009)
Phase 1/2 · 29 women with HA
Kisspeptin-54 induces LH release in hypothalamic amenorrhea
Overview
Kisspeptin’s discovery in 2003 transformed reproductive neuroendocrinology by identifying the long-sought gating mechanism for GnRH secretion. It is now understood that essentially all signals that modulate reproductive function — from nutritional status to stress to seasonal photoperiod — ultimately act through kisspeptin neurons in the hypothalamus.
Clinical Applications in Development
The most advanced clinical applications are in reproductive medicine: induction of ovulation (as an alternative to hCG in IVF protocols), diagnosis of HPG axis disorders, and treatment of hypothalamic amenorrhea. A key advantage over hCG-based ovulation induction is potentially reduced ovarian hyperstimulation syndrome risk.
Diagnostic Value
Kisspeptin testing is emerging as a diagnostic tool for HPG axis integrity — a kisspeptin stimulation test can distinguish between central hypogonadism subtypes and assess pituitary reserve. This diagnostic application may reach clinical practice ahead of therapeutic applications.
Metabolic-Reproductive Connection
Kisspeptin neurons in the arcuate nucleus co-express neurokinin B and dynorphin (KNDy neurons) and receive leptin, insulin, and nutrient signals. This positions kisspeptin as a critical link between metabolic status (energy availability) and reproductive function — explaining why extreme weight loss or malnutrition suppresses reproduction.
Regulatory Status
Research OnlyNot FDA-approved; significant human trial data exists; no regulatory approval
Safety Profile
Side Effects
- •Nausea (IV bolus)
- •Flushing
- •Transient blood pressure changes
Contraindications
- •Hormone-sensitive cancers
- •Pregnancy (GnRH axis manipulation)
Drug Interactions
- •GnRH agonists/antagonists
- •Sex hormone therapies
Primary Uses
Related Peptides
Weekly Briefing
Regulatory updates + new study breakdowns.
For Practitioners
Do you prescribe Kisspeptin?
Get in front of patients who've already researched this protocol and are ready to consult. Featured listings from $199/mo.
Get Listed →