View source for Antiestrogen

{{Short description|Class of drugs}}
{{Infobox drug class
| Image = Fulvestrant.svg
| ImageClass = skin-invert-image
| Alt = 
| Caption = [[Fulvestrant]], a [[steroid]]al 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 = [[Steroid]]al; [[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 [[drug]]s which prevent [[estrogen]]s like [[estradiol]] from mediating their [[biological effect]]s in the body. They act by [[receptor antagonist|blocking]] the [[estrogen receptor]] (ER) and/or [[steroidogenesis inhibitor|inhibiting]] or [[antigonadotropin|suppressing]] estrogen [[biosynthesis|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-hormonal agent|sex hormone antagonist]]s, the others being [[antiandrogen]]s and [[antiprogestogen]]s.<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 steroid hormones, estrogen, from binding to the estrogen receptors leading to the decrease of estrogen levels.<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 | pages = 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 modulator]]s (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 inhibitor]]s (AIs) like [[anastrozole]], and [[antigonadotropin]]s including [[androgen]]s/[[anabolic steroid]]s, [[progestogen]]s, and [[GnRH analogue]]s.

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 inhibitor]]s 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 = 9780127098715 | 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 (female-to-male)|hormone replacement therapy]] for [[transgender men]]

==Side effects==
In [[Woman|women]], the [[side effect]]s of antiestrogens include [[hot flash]]es, [[osteoporosis]], [[breast atrophy]], [[vaginal dryness]], and [[vaginal atrophy]]. In addition, they may cause [[depression (mood)|depression]] and reduced [[libido]].

==Pharmacology==
Antiestrogens act as [[receptor antagonist|antagonist]]s of the [[estrogen receptor]]s, [[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 | url = https://pubmed.ncbi.nlm.nih.gov/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]]