GnRH agonists: gonadorelin, leuprolide and nafarelin

Gonadotropin-releasing hormone (GnRH), a decapeptide synthesized and released by the hypothalamus, regulates production and release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the adenohypophysis. Parenterally administered GnRH was initially used diagnostically as a test of adenohypophyseal reserve of LH and FSH. Subsequently, native GnRH was used therapeutically to treat hypothalamic hypogonadal and infertility states in both men and women. Because of the low potency and short half-life of native GnRH, long-acting, potent analogs have been developed that suppress secretion of native pituitary gonadotropins, resulting in medical gonadectomy. When administered parenterally and, more recently, intranasally, these compounds are useful in the management of prostate and breast carcinoma, endometriosis and uterine leiomyomata, precocious puberty and nontumorous ovarian hyperandrogenic syndromes.