[Clinical consequences of the administration of a GnRH antagonist during the menstrual cycle]

GnRH is the native decapeptide which initiates the reproductive cascade. It is synthesized in a loose network of hypothalamic neurons and released into the hypothalamo-pituitary portal blood system in a pulsatile manner. The main physiologic actions of GnRH include the synthesis and release of LH and FSH. Analogs are synthetic versions of GnRH with various amino acid substitutions. These substitutions serve to increase their half-life and to increase their affinity for the GnRH receptor. There are two types of analog: GnRH agonists and GnRH antagonists. GnRH agonists behave like GnRH and are initially stimulatory ("flare up"). GnRH antagonists block the effects of GnRH and are inhibitory. When GnRH antagonists bind to the GnRH receptor they do not initiate the normal cascade of intracellular events, they prevent GnRH from gaining access to the receptor and prevent the above cascade from occuring. Consequently there is no "Flare Effect" and levels of LH and FSH begin immediately to fall. GnRH antagonists do not cause GnRH receptor downregulation: the pituitary remains responsive to GnRH or GnRH agonist administration. The degree of suppression of circulating LH and FSH is dependent on circulating levels of the GnRH antagonist. Administration of GnRH antagonist produces suppression of endogenous LH and FSH at all phases of the cycle. The degree of suppression is dependent on the amount of GnRH antagonist administered. The suppression of endogenous LH and FSH produced by GnRH antagonist can be overridden by GnRH or GnRH agonist.