{"paper_id":"ebb645a3-02e8-4d83-a553-c8a48a4b6144","body_text":"ABSTRACT\nIntroduction\nEndometriosis 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.\nAreas covered\nBy 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.\nExpert opinion\nGnRHagonists 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.\nArticle highlights\nIn women who do not respond to the first-line therapies, endometriosis can be treated by inducing hypoestrogenism with the GnRHanalogs. However, this therapeutical strategy shows some disadvantages:\nnon-immediate suppression of gonadotropins and estradiol;\ncomplex ways of administrations, such as daily subcutaneous injections, more than one daily intranasal spray, depot intramuscular or subcutaneous injections either every month or every 3–4 months;\nhypoestrogenism-dependent side effects, disabling the quality of life and the health, especially affecting the bone. However, all of these adverse effects can be antagonized by the concomitant administration of estrogen and progestin (add back therapy).\nThe peptide GnRHantagonists over the GnRHagonists offer the advantage of inducing an immediate suppression of gonadotropins and estradiol, but like the GnRHagonists:\nrequire complex ways of administrations.\nneed to counteract the hypoestrogenism side effects with add-back therapy.\nThe discovery of non-peptide GnRHantagonists opens a new scenario in the treatment of endometriosis:\nimmediate suppression of gonadotropins and estradiol.\noral administration unlike complex ways of administrations of GnRHagonists and peptide GnRH antagonists.\ndecrease in gonadotropins and estradiol related to doses of the non-peptide GnRH antagonist.\nrapid reversibility of related-hypoestrogenism.\nDeclaration of interest\nThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.\nReviewer disclosure\nPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.\nAcknowledgments\nThe authors thank K Jenkins for revising the English language of the manuscript.","source_license":"CC0","license_restricted":false}