GnRH Agonist vs Antagonist

Both classes end at the same place, a suppressed gonadal axis, but reach it by opposite routes. Agonists such as leuprolide, goserelin, triptorelin and nafarelin carry a D-amino acid at position 6, a change that blocks the main cleavage site and extends duration enough to give the pituitary continuous rather than pulsatile receptor occupancy. The gonadotrope first releases its stored LH and FSH, then desensitises and downregulates, and only then does output fall. Antagonists such as cetrorelix, ganirelix, degarelix and oral relugolix occupy the receptor competitively from the first dose, so gonadotropins fall within hours to days with no preceding rise.

A leuprolide depot in prostate cancer produces a testosterone surge over the first week or two before castrate concentrations are reached at around three to four weeks, and that flare can transiently worsen bone pain, spinal cord compression or bladder outlet obstruction, which is why an antiandrogen is usually given around initiation. Degarelix reaches castrate testosterone within a few days without any surge, and relugolix, approved in the United States in 2020, delivers antagonism orally.

The choice turns on how fast suppression is needed, whether a flare is tolerable, and how quickly the axis must recover. Depot agonists offer long dosing intervals and decades of use; antagonists immediate onset and a shorter tail after stopping.

The error worth naming treats the phrase GnRH analogue as if it described one thing, since agonist and antagonist have opposite acute effects and a summary reporting only the eventual suppression hides the flare entirely. A related confusion equates an agonist depot with pulsatile GnRH delivered by pump: the molecule class is the same and the endocrine outcome opposite, because the pattern of delivery, not the ligand, decides whether the pituitary is driven or shut down.