Long Term Experience with a Superactive GnRH Analog in the Treatment of Precocious Puberty

Since 1960 we have treated in our Institute 209 children with central (true) precocious puberty (CPP). Out of these only 2 male patients had CNS tumors (optic nerve glioma and glioblastoma), in the others the process was idiopathic. Depending upon the time period, the drugs used varied (Table 1). The results obtained TABLE 1 Drugs employed in the treatment of 209 children (149 girls, 60 boys) with central precocious puberty Year Drug Patients Girls Treated Boys 1960–1967 Medroxyprogesterone acetate inj. (Upjohn) 4 1 1967–1980 Cyproterone acetate p.o. (Schering) 100 53 1980–1987 Gn-RH analog ([D-Trp6-LHRH)a Aqueous daily s.c. inj.b (Schally) 21 4 Depot monthly i.m. inj. (Ferring) 36 1 a 15 patients were previously treated with cyproterone acetate b 7 patients were switched from daily to monthly injections. with medroxyprogesterone acetate (Depo-Provera, Upjohn) were not satisfactory [1]. The first drug which seemed to have long-term effects in suppressing the precocious gonadotropin secretion, slowing the rate of skeletal maturation and thus prolonging the period of growth, was cyproterone acetate (Androcur, Schering) [2]. However, with increasing experience it was observed that on prolonged administration, “escape phenomena” occurred and that an improved final height was often not achieved. In 1980, trying in children with hypogonadotropic hypogonadism the long-term stimulatory activity of a superactive GnRH analog ([D-Trp6] LHRH) we observed that the stimulatory phase was followed by a blocking effect [3], therefore, immediately tried to find out whether this property of paradoxical refractoriness of the gonadotropic cells induced by long-term use of a GnRH agonist could be exploited in the treatment of precocious puberty