{{Short description|Class of drugs}} {{Infobox drug class | Image = Fulvestrant.svg | ImageClass = skin-invert-image | Alt = | Caption = Fulvestrant, a steroidal antiestrogen and a drug used in the treatment of breast cancer. | Width = 250px | Synonyms = Estrogen antagonists; Estrogen blockers; Estradiol antagonists <!-- Class identifiers --> | Use = Breast cancer; Infertility; Male hypogonadism; Gynecomastia; transgender men | ATC_prefix = L02BA | Biological_target = Estrogen receptor | Chemical_class = Steroidal; Nonsteroidal (triphenylethylene, others) <!-- Clinical data --> | Drugs.com = | Consumer_Reports = | medicinenet = | rxlist = <!-- External links --> | MeshID = D020847 }}
'''Antiestrogens''', also known as '''estrogen antagonists''' or '''estrogen blockers''', are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production.<ref name="urlDefinition of antiestrogen - NCI Dictionary of Cancer Terms, Definition of antiestrogen - NCI Dictionary of Cancer Terms">{{cite web |url=http://www.cancer.gov/dictionary/?CdrID=44813 |title=Definition of antiestrogen - NCI Dictionary of Cancer Terms, Definition of antiestrogen - NCI Dictionary of Cancer Terms }},</ref><ref>{{DorlandsDict|one/000006027|antiestrogen}}</ref> Antiestrogens are one of three types of sex hormone antagonists, the others being antiandrogens and antiprogestogens.<ref name="Nath2006">{{cite book| vauthors = Nath JL |title=Using Medical Terminology: A Practical Approach |url=https://archive.org/details/usingmedicalterm0000nath |url-access=registration |year=2006 |publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-4868-1|pages=[https://archive.org/details/usingmedicalterm0000nath/page/977 977]–}}</ref> Antiestrogens are commonly used to stop estrogens from binding to the estrogen receptors, leading to a decrease of the effects of estrogens.<ref>{{cite journal | vauthors = McKeage K, Curran MP, Plosker GL | title = Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy | journal = Drugs | volume = 64 | issue = 6 | pages = 633–48 | date = 2004-03-01 | pmid = 15018596 | doi = 10.2165/00003495-200464060-00009 | s2cid = 242916244 }}</ref> Decreased levels of estrogen can lead to complications in sexual development.<ref>{{cite journal | vauthors = Amenyogbe E, Chen G, Wang Z, Lu X, Lin M, Lin AY | title = A Review on Sex Steroid Hormone Estrogen Receptors in Mammals and Fish | journal = International Journal of Endocrinology | volume = 2020 | article-number = 5386193 | date = 2020-02-07 | pmid = 32089683 | pmc = 7029290 | doi = 10.1155/2020/5386193 | doi-access = free }}</ref>
==Types and examples== Antiestrogens include selective estrogen receptor modulators (SERMs) like tamoxifen, clomifene, and raloxifene, the ER silent antagonist and selective estrogen receptor degrader (SERD) fulvestrant,<ref name="OttowWeinmann2008">{{cite book| vauthors = Ottow E, Weinmann H |title=Nuclear Receptors as Drug Targets|url=https://books.google.com/books?id=iATfLbPgRugC&pg=PA164|date=8 September 2008|publisher=John Wiley & Sons|isbn=978-3-527-62330-3|pages=164–165}}</ref><ref name="ChabnerLongo2010">{{cite book| vauthors = Chabner BA, Longo DL |title=Cancer Chemotherapy and Biotherapy: Principles and Practice|url=https://books.google.com/books?id=WL4arNFsQa8C&pg=PA660|date=8 November 2010|publisher=Lippincott Williams & Wilkins|isbn=978-1-60547-431-1|pages=660–}}</ref> aromatase inhibitors (AIs) like anastrozole, and antigonadotropins including androgens/anabolic steroids, progestogens, and GnRH analogues.
Estrogen receptors (ER) like ERα and ERβ include activation function 1 (AF1) domain and activation function 2 (AF2) domain in which SERMS act as antagonists for the AF2 domain, while "pure" antiestrogens like ICI 182,780 and ICI 164,384 are antagonists for the AF1 and AF2 domains.<ref>{{Cite journal|last1=Pike|first1=Ashley C.W.|last2=Brzozowski|first2=A.Marek|last3=Walton|first3=Julia|last4=Hubbard|first4=Roderick E.|last5=Thorsell|first5=Ann-Gerd|last6=Li|first6=Yi-Lin|last7=Gustafsson|first7=Jan-Åke|last8=Carlquist|first8=Mats|date=2001-02-01|title=Structural Insights into the Mode of Action of a Pure Antiestrogen|journal=Structure|language=en|volume=9|issue=2|pages=145–153|doi=10.1016/S0969-2126(01)00568-8|pmid=11250199|issn=0969-2126|doi-access=free}}</ref>
Although aromatase inhibitors and antigonadotropins can be considered antiestrogens by some definitions, they are often treated as distinct classes.<ref name="pmid16112269">{{cite book | vauthors = Riggins RB, Bouton AH, Liu MC, Clarke R | title = Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer | volume = 71 | pages = 201–37 | year = 2005 | pmid = 16112269 | doi = 10.1016/S0083-6729(05)71007-4 | isbn = 978-0-12-709871-5 | series = Vitamins & Hormones }}</ref> Aromatase inhibitors and antigonadotropins reduce the ''production'' of estrogen, while the term "antiestrogen" is often reserved for agents reducing the ''response'' to estrogen.<ref name="pmid14633737">{{cite journal | vauthors = Thiantanawat A, Long BJ, Brodie AM | title = Signaling pathways of apoptosis activated by aromatase inhibitors and antiestrogens | journal = Cancer Research | volume = 63 | issue = 22 | pages = 8037–50 | date = November 2003 | pmid = 14633737 | url = https://cancerres.aacrjournals.org/content/63/22/8037.short }}</ref>
==Medical uses== Antiestrogens are used for:
* Estrogen deprivation therapy in the treatment of ER-positive breast cancer * Ovulation induction in infertility due to anovulation * Male hypogonadism * Gynecomastia (breast development in men) * A component of hormone replacement therapy for transgender men
==Side effects== In women, the side effects of antiestrogens include hot flashes, osteoporosis, breast atrophy, vaginal dryness, and vaginal atrophy. In addition, they may cause depression and reduced libido.
==Pharmacology== Antiestrogens act as antagonists of the estrogen receptors, ERα and ERβ.
{{Affinities of estrogen receptor ligands for the ERα and ERβ}}
==History== The first nonsteroidal antiestrogen was discovered by Lerner and coworkers in 1958.<ref>{{cite journal | vauthors = MacGregor JI, Jordan VC | title = Basic guide to the mechanisms of antiestrogen action | journal = Pharmacological Reviews | volume = 50 | issue = 2 | pages = 151–96 | date = June 1998 | pmid = 9647865 }}</ref> Ethamoxytriphetol (MER-25) was the first antagonist of the ER to be discovered,<ref name="MaximovMcDaniel2013">{{cite book| vauthors = Maximov PY, McDaniel RE, Jordan VC |title=Tamoxifen: Pioneering Medicine in Breast Cancer|url=https://books.google.com/books?id=p-W5BAAAQBAJ&pg=PA7|date=23 July 2013|publisher=Springer Science & Business Media|isbn=978-3-0348-0664-0|pages=7–}}</ref> followed by clomifene and tamoxifen.<ref name="Jordan2013">{{cite book| vauthors = Jordan VC |title=Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health: Progress and Promise|url=https://books.google.com/books?id=ZM26CgAAQBAJ&pg=PA7|date=27 May 2013|publisher=World Scientific|isbn=978-1-84816-959-3|pages=7,112}}</ref><ref name="Sneader2005">{{cite book|vauthors = Sneader W |title=Drug Discovery: A History|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA198|date=23 June 2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2|pages=198–199}}</ref>
== See also == * Antiestrogen withdrawal response * Estrogen synthesis inhibitor
== References == {{Reflist}}
== External links == * {{Commons category-inline|Antiestrogens}} {{NCI-cancer-dict}}
{{Estrogens and antiestrogens}} {{Estrogen receptor modulators}}
Category:Antiestrogens Category:Hormonal antineoplastic drugs Category:Progonadotropins