title: The extrapituitary effects of GnRH antagonists and their potential clinical implications: a narrated review.
abstract: Potential roles of gonadotropin-releasing hormone (GnRH) antagonists on GnRH/GnRH receptor systems and their effects on the extrapituitary tissues are largely elusive. In this narrated review, we summarized the systemic effects of GnRH antagonists on ovary, endometrium, embryo implantation, placental development, fetal teratogenicity, reproductive tissue cancer cells, and heart while briefly reviewing the GnRH and GnRH receptor system. GnRH antagonists may have direct effects on ovarian granulosa cells. Data are conflicting regarding their effects on endometrial receptivity. The GnRH antagonists may potentially have detrimental effect on early placentation by decreasing the invasive ability of cytotrophoblasts if the exposure to them occurs during early pregnancy. The GnRH antagonists were not found to increase the rates of congenital malformations. Comparative clinical data are required to explore their systemic effects on various extrapituitary tissues such as on cardiac function in the long term as well as their potential use in other human cancers that express GnRH receptors.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. orkun.tan@utsouthwestern.edu
authors.forename: Orkun
authors.initials: O
authors.lastname: Tan
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Carr
authors.forename: Victor E
authors.initials: VE
authors.lastname: Beshay
authors.forename: Orhan
authors.initials: O
authors.lastname: Bukulmez
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D018873:Pregnancy Rate / Q000639:trends; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome; D014565:Urogenital Neoplasms / Q000188:drug therapy / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006727:Hormone Antagonists; D011966:Receptors, LHRH