The chronic administration of the long-acting
LHRH agonist analog D-Ser(TBU)6-LHRH-EA10 (
HOE 766,
Buserelin) suppresses pituitary
gonadotropin secretion. Since a similar analog was shown to be effective in the short term parenteral treatment of idiopathic
precocious puberty in girls (10), we used
Buserelin both intranasally and sc to treat patients of both sexes with idiopathic and secondary
central precocious puberty to test its efficacy, safety, and potential for long term use. Six girls and two boys presented with advanced skeletal maturity, accelerated growth velocity, Tanner stage II-IV pubertal development, and pubertal levels of sex
steroids and
gonadotropins. Patients were treated for 6 months sc and up to 5 months intranasally. Optimal doses ranged from 10-20 micrograms/kg X day in girls and 30 micrograms/kg X day in boys, with marked individual variation. During sc
therapy, there was significant suppression of growth velocity (P less than 0.001), serum
gonadotropins (P less than 0.001),
17 beta-estradiol (P less than 0.005), and
testosterone as well as clinical and behavioral improvement. The rate of bone maturation was reduced. All effects were reversed after discontinuation of
therapy for 1 month in one girl. No reduction in efficacy was seen after changing four girls and one boy to intranasal
therapy, but improved acceptability and compliance were reported by parents. Apart from withdrawal
bleeding in one girl and transient acceleration of puberty in two patients during the initial phase of treatment, no serious unwanted effects occurred.
Antibodies to native
LHRH were not detected after 6 months of
therapy. These results confirm the efficacy and safety of
Buserelin by intranasal and sc routes in patients with
sexual precocity and indicate a need for long term studies.