Natural GnRH administered in hourly pulses (to mimic hypothalamic secretion) is effective in treating hypogonadotropic hypogonadism (e.g., in anorexia nervosa, hypothalamic amenorrhea, and Kallman's syndrome), undescended testes (cryptorchidism), and delayed puberty (Fig. 115-4).

GnRH analogues are used extensively as intervention therapies in a wide spectrum of pathologies, which is reflected in annual sales of about $2 billion. Long-term pharmacologic administration of GnRH agonists induces gonadotrope desensitization and inhibition of gonadotropin secretion, resulting in inhibition of gonadal sex steroid hormones and gametogenesis (see Fig. 115-4). This is a slow process, requiring 1 to 2 weeks, and induces stimulation before desensitization occurs. In contrast, GnRH antagonists have immediate inhibition of gonadotropins, with the rate of decline equal to that of their half-lives. Consequently, GnRH …