Pharmacokinetic considerations for gonadotropin-releasing hormone agonists and antagonists to treat endometriosis.

Introduction: Endometriosis is a chronic disease characterized by endometriotic cells implanted outside the uterus triggering a chronic inflammatory state. Estradiol stimulates the endometriotic implants, which overexpress estrogen receptor β. Lowering estradiol levels to a range within 40-50 pg/ml allows antagonizing the growth of endometriotic implants and counteracting its-related disabling symptoms.

Areas covered: By blocking the Gonadotropin-Releasing-Hormone (GnRH) receptors, GnRHagonists, peptide GnRHantagonists, non-peptide GnRHantagonists induce hypoestrogenism, due to the suppression of pituitary gonadotropins. This manuscript provides the results of an electronic literature search on pharmacological features of GnRHagonists and GnRHantagonists to treat endometriosis. Hypoestrogenism-dependent side effects can be counteracted by concomitant estrogen and progestin compounds (add-back therapy). GnRHagonists chronic administration induces hypoestrogenism after 10-12 days, since initial administrations stimulate gonadotropin rise (flare-up effect). Peptide GnRHantagonists quickly block GnRH-receptors inducing an immediate hypoestrogenism. Similarly to GnRHagonists, their peptide structure impedes the oral administration. The non-peptide GnRHantagonists have the advantage both of being taken orally and inducing a rapid dose-dependent hypoestrogenism.

Expert opinion: GnRHagonists and peptide GnRHantagonists are effective to treat endometriosis, but require complex ways of administration. Non-peptide GnRHantagonists offer more important prospects in the tailored medical treatment of endometriosis, given their rapid onset of action and their oral way of administration.