Pulsatile GnRH treatment in boys and girls with idiopathic hypogonadotrophic hypogonadism.

Abstract

In order to induce pubertal development, low-dose, pulsatile gonadotrophin-releasing hormone (GnRH) was administered i.v. in adolescent boys and girls with an isolated hypogonadotrophic hypogonadism. The first study included GnRH treatment in 21 male patients with the goal of initiating testicular growth and spermatogenesis; in the second study, GnRH was administered in three adolescent boys and two girls in an increasing pulse frequency as well as pulse dose in order to imitate the 'physiological' pubertal changes. In the first study gonadotrophin and testosterone levels increased in all patients, and testicular growth also occurred. When GnRH treatment was discontinued spermatogenesis was present in 14 out of the 17 patients examined, and was observed in another patient during subsequent human chorionic gonadotrophin (HCG) treatment. Ultimately, 15 out of the 19 patients developed spermatozoa. In the second study, small increases in luteinizing hormone (LH) and follicle stimulating hormone (FSH) were observed during a low-frequency GnRH schedule, followed by a further rise during the 'physiological' schedule with a 90-min pulse interval; testosterone and oestradiol also increased. An increased secretion of growth hormone occurred only in boys during GnRH treatment, after their testosterone levels had increased. In girls, none of the GnRH treatment schedules was associated with an increase in growth hormone. Pulsatile GnRH treatment is thus feasible as a method of inducing testicular growth and spermatogenesis. A GnRH treatment schedule with an increasing pulse frequency and pulse dose can imitate the 'physiological' pubertal changing pattern of gonadotrophins just as well as the use of sex steroid. However, with respect to growth hormone secretion, GnRH will induce an increase in boys only.