Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. effects on somatic growth and skeletal maturation

For the child with precocious puberty, in the absence of a correctable anatomic lesion, the goal of therapy is suppression of gonadal function in order to arrest or reverse secondary sexual development, decrease the linear growth rate to a normal prepubertal velocity, and slow skeletal maturation to prevent short stature caused by premature epiphyseal fusion. So far, no therapeutic approach has achieved al these objectives. In earlier short-term studies, the present authors have shown that a potent agonist of the gonadotropin-reteasing hormone, D-Trp ⁶-Pro⁹-NEt-LHRH (LHRH_a), can decrease the responsiveness of the pituitary to kiteinizing hormone-releasing hormone (LHRH) and thereby reversibly suppress pubertal gonadotropin and sex steroid levels over an 8-week period in patients with idiopathic precocious puberty. They now report the effects of LHRH. on secondary sexual development, statural growth, skeletal maturation, and predicated adult height in nine girls with central idiopathic or neurogenic precocious puberty, who were treated continuously for 18 months. Two patients had received earlier treatment with other drugs. The involution of secondary sexual characteristics, previously reported after short-term therapy, was maintained throughout the 18 months of treatment. Menstruation ceased in al menstruating patients. The amount of heavy tissue decreased or was stabilized in al, and breast development regressed by a full Tanner stage in two patients (both had been in Tanner stage III or less before treatment). Pubic hair diminished in two subjects whose dehydroepiandrosterone sulfate levels remained premenarcheal (i.e., below 60 μg/dl. but increased by a ful Tanner stage in two of the five patients who had had levels above 60 μq/ dl before treatment. LHRH_a. therapy did not appear to interfere with the progression of established adrenarche, and dehydroepiandrosterone sulfate levels rose in four of five patients who had had levels above 60 μg/dl before therapy. Before treatment, al patients had serum gonadotropin levels that were elevated into the pubertal ranges, with detectable nocturnal gonadotropin pulsations and a brisk rise in gonadotropin levels in response to LHRH. Initiation of treatment with LHRH_a.