Therapeutic potential of GnRH antagonists in the treatment of precocious puberty.

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.