Treatment of true precocious puberty with a potent luteinizing hormone-releasing factor agonist: Effect on growth, sexual maturation, pelvic sonography, and the hypothalamic-pituitary-gonadal axis

We used the LHRH agonist D-Trp⁶-Pro⁶-N-ethylamide LHRH (LHRH-A) to treat 19 children (12 girls and 7 boys) with true precocious puberty. Fourteen patients had idiopathic true precocious puberty, 4 had a hamartoma of the tuber cinereum, and 1 had a hypothalamic astrocytoma. Basal gonadotropin secretion and responses to native LHRH decreased within 1 week of initiation LHRH-A therapy, and sex steroid secretion decreased within 2 weeks to or within the prepubertal range. Ultrasonographic evaluation of the uterus indicated a postmenarchal size and shape in all 11 girls studied before treatment, which reverted to prepubertal size and configuration in 5 girls during LHRH-A therapy. The enlarged ovaries decreased in size and the multiple ovarian follicular cysts regressed. Sexual characteristics ceased advancing or reverted toward the prepubertal state in all patients receiving therapy for 6-36 months. All 5 girls with menarche before therapy had no further menses. Three girls had hot flashes after LHRH-A-induced reduction of the plasma estradiol concentration. Height velocity, SDs above the mean height velocity for age, and SDs above the mean height for age decreased during LHRH-A therapy; the velocity of skeletal maturation decreased after 12 months of LHRH-A therapy and was sustained during continued therapy over 18-36 months. In 4 patients, a subnormal growth rate (<4.5 cm/yr) occurred during LHRH-A therapy. Six patients had cutaneous reactions of LHRH-A, but no demonstrable circulating antibodies to LHRH-A. In 2 patients in whom LHRH-A therapy was discontinued because of skin reactions precocious sexual maturation resumed at the previous rate for the ensuing 6-12 months; subsequently, they were desensitized to LHRH-A, and during a second course of therapy, their secondary sexual development and sex steroid levels again quickly decreased. LHRH-A proved an effective and safe treatment for true precocious puberty in boys as well as girls with central precocious puberty whether of the idiopathic type or secondary to a hamartoma of the tuber cinereum or a hypothalamic neoplasm.