Short-Term Treatment of Idiopathic Precocious Puberty with a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone: A Preliminary Report

The uncoupling of pituitary stimulation and response observed in adults during administration of the luteinizing hormone-releasing hormone analogue, D-Trp⁶-Pro⁹-NEt-LHRH (LHRH_a) suggested that this drug might be useful in treating precocious puberty. We treated five girls with idiopathic precocious puberty (ages two to eight) for eight weeks with daily subcutaneous injections of LHRH_a. The patients had Tanner II to IV pubertal development, advanced bone age, an estrogen effect on vaginal smear, measurable basal gonadotropin levels with pulsed nocturnal secretion, and a pubertal gonadotropin response to LHRH. Irregular vaginal bleeding was present in three patients. LHRH_a significantly decreased basal (P<0.025) and LHRH-stimulated (P<0.01) gonadotropin levels as well as serum estradiol (P<0.05). The vaginal maturation-index score, which reflects the estrogen effect, fell by 25 per cent. Eight weeks after stopping treatment, all hormonal values and the vaginal maturation index had returned to pretreatment levels. These favorable short-term results will need further study before the benefits and risks of chronic treatment with LHRH_a can be adequately assessed. (N Engl J Med. 1981; 305:1546–50.) PUBERTY is initiated by the pulsed nocturnal secretion of gonadotropins. These gonadotropin pulses, resulting from the episodic release of luteinizing hormone-releasing hormone (LHRH) by the hypothalamus, stimulate gonadal sex-steroid secretion, which leads to the secondary sexual changes characteristic of puberty.¹ This process begins prematurely in idiopathic precocious puberty. The premature occurrence of pubertal maturation adversely affects subsequent development in several ways. Adult stature may be compromised because of accelerated epiphyseal closure. Adverse psychosocial effects (including libido, the need for contraception, and rejection by peers) may be profound for both the child and the family. An adequate treatment for this disorder. . .