Pituitary-gonadal axis activation depends upon pulsatile hypothalamic
gonadotropin-releasing hormone (
GnRH) secretion. This phenomenon has led to clinical use of
GnRH agonists in the treatment of
central precocious puberty.
GnRH analogues contain substitutions of the native decapeptide. Depending upon the substitutions, the analogues have
GnRH agonistic or antagonistic properties. The pharmacokinetics of
GnRH agonists, the established treatment of
precocious puberty, includes an initial 'flare-up' of the pituitary-gonadal axis, followed by a reduced luteinising
hormone secretion by desensitisation of pituitary
GnRH receptors. Antagonistic
GnRH analogues act by competitive binding to the pituitary
GnRH receptors, thereby preventing the action of endogenous
GnRH - theoretically offering a more direct and dose-dependent treatment alternative. The antagonist available today in Germany is a concomitant in assisted reproduction with only 1 - 3 days duration. However, long-acting
depot preparations of other
GnRH antagonists are in primate-testing phase. Our animal tests indicate strong potential for the development and testing of long-acting
depot preparations of
GnRH antagonists in treating
precocious puberty.