Kisspeptin-10

Kisspeptin is a neuropeptide produced by hypothalamic KNDy neurons (kisspeptin/neurokinin B/dynorphin) that represents the primary upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis. Kisspeptin-10 is the biologically active 10-amino acid C-terminal fragment. It binds to KISS1R (GPR54) receptors on GnRH neurons, triggering pulsatile GnRH release — which in turn drives LH and FSH secretion from the pituitary, ultimately stimulating testosterone production in the testes. This mechanism is upstream of all other testosterone-supporting interventions: Kisspeptin addresses the hypothalamic pulse generator directly. Clinical research has established its role in puberty initiation, reproductive function, and as a diagnostic and therapeutic tool for hypogonadotropic hypogonadism.

Kisspeptin's role as the gatekeeper of reproductive function is well-established — the discovery of its role in GnRH regulation earned its discoverers the prestigious Aldo Mastroianni Prize. Clinical research at King's College London (Dhillo et al.) and MIT has established its utility as a diagnostic tool in reproductive endocrinology and a therapeutic candidate for hypothalamic hypogonadism. Multiple human trials demonstrate reliable LH pulse and testosterone elevation following Kisspeptin-10 administration. The application to age-related testosterone decline (where GnRH pulse amplitude and frequency reduce) is mechanistically sound but remains in early clinical investigation. Growing use in integrative hormone medicine alongside or as an alternative to clomiphene for men seeking testosterone restoration without exogenous hormone use.

4–8 weeks — pulsatile administration important; continuous use causes receptor desensitisation