Editing Antiandrogen (section)

===Timeline===
The following is a timeline of events in the history of antiandrogens:<ref name="pmid29730201">{{cite journal | vauthors = Crawford ED, Schellhammer PF, McLeod DG, Moul JW, Higano CS, Shore N, Denis L, Iversen P, Eisenberger MA, Labrie F | title = Androgen Receptor Targeted Treatments of Prostate Cancer: 35 Years of Progress with Antiandrogens | journal = J. Urol. | volume = 200 | issue = 5 | pages = 956–966 | date = November 2018 | pmid = 29730201 | doi = 10.1016/j.juro.2018.04.083 | s2cid = 19162538 }}</ref>

* 1941: Hudgins and Hodges show that androgen deprivation via high-dose estrogen therapy or surgical castration treats prostate cancer
* 1957: The steroidal antiandrogen spironolactone is first synthesized<ref name="pmid28634268">{{cite journal | vauthors = Kolkhof P, Bärfacker L | title = 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development | journal = J. Endocrinol. | volume = 234 | issue = 1 | pages = T125–T140 | date = July 2017 | pmid = 28634268 | pmc = 5488394 | doi = 10.1530/JOE-16-0600 }}</ref>
* 1960: Spironolactone is first introduced for medical use, as an antimineralocorticoid<ref name="pmid28634268" />
* 1961: The steroidal antiandrogen cyproterone acetate is first synthesized<ref name="pmid9476091">{{cite journal | vauthors = Pucci E, Petraglia F | title = Treatment of androgen excess in females: yesterday, today and tomorrow | journal = Gynecol. Endocrinol. | volume = 11 | issue = 6 | pages = 411–33 | date = December 1997 | pmid = 9476091 | doi = 10.3109/09513599709152569 }}</ref>
* 1962: Spironolactone is first reported to produce gynecomastia in men<ref name="pmid28634268" /><ref name="Smith1962">{{cite journal| vauthors = Smith WG |title=Spironolactone and gynaecomastia|journal=The Lancet|volume=280|issue=7261|year=1962|pages=886|issn=0140-6736|doi=10.1016/S0140-6736(62)90668-2}}</ref>
* 1966: Benorterone is the first known antiandrogen to be studied clinically, to treat acne and hirsutism in women<ref name="pmid148431">{{cite journal | vauthors = Stewart ME, Pochi PE | title = Antiandrogens and the skin | journal = Int. J. Dermatol. | volume = 17 | issue = 3 | pages = 167–79 | date = April 1978 | pmid = 148431 | doi = 10.1111/j.1365-4362.1978.tb06057.x | s2cid = 43649686 }}</ref><ref name="pmid4225258">{{cite journal | vauthors = Zarate A, Mahesh VB, Greenblatt RB | title = Effect of an antiandrogen, 17-alpha-methyl-B-nortestosterone, on acne and hirsutism | journal = J. Clin. Endocrinol. Metab. | volume = 26 | issue = 12 | pages = 1394–8 | date = December 1966 | pmid = 4225258 | doi = 10.1210/jcem-26-12-1394 }}</ref>
* 1963: The antiandrogenic activity of cyproterone acetate is discovered<ref name="Neumann1996">{{cite book| vauthors = Neumann F |title=Antiandrogens in Prostate Cancer|chapter=Pharmacology of Cyproterone Acetate — A Short Review|year=1996|pages=31–44|doi=10.1007/978-3-642-45745-6_3|isbn=978-3-642-45747-0}}</ref><ref name="pmid14071315">{{cite journal | vauthors = Hamada H, Neumann F, Junkmann K | title = Intrauterine Antimaskuline Beeinflussung von Rattenfeten Durch ein Stark Gestagen Wirksames Steroid | language = de | journal = Acta Endocrinologica | volume = 44 | issue = 3 | pages = 380–388 | date = November 1963 | pmid = 14071315 | doi = 10.1530/acta.0.0440380 | trans-title = Intrauterine antimasculine influence of Rat Fetuses by Birtue of a Powerful Steroid Acting as a Progestogen }}</ref>
* 1967: A known antiandrogen, benorterone, is first reported to induce gynecomastia in males<ref name="pmid148431" />
* 1967: The first-generation nonsteroidal antiandrogen flutamide is first synthesized
* 1967: Cyproterone acetate was first studied clinically, to treat sexual deviance in men<ref name="pmid20459370">{{cite journal | vauthors = Thibaut F, De La Barra F, Gordon H, Cosyns P, Bradford JM | title = The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of paraphilias | journal = World J. Biol. Psychiatry | volume = 11 | issue = 4 | pages = 604–55 | date = June 2010 | pmid = 20459370 | doi = 10.3109/15622971003671628 | s2cid = 14949511 }}</ref>
* 1969: Cyproterone acetate was first studied in the treatment of acne, hirsutism, seborrhea, and scalp hair loss in women<ref name="pmid4304873">{{cite journal | vauthors = Hammerstein J, Cupceancu B | title = Behandlung des Hirsutismus mit Cyproteronacetat | trans-title = Management of hirsutism using cyproterone acetate | language = de | journal = Deutsche Medizinische Wochenschrift | volume = 94 | issue = 16 | pages = 829–34 | date = April 1969 | issn = 0012-0472 | pmid = 4304873 | doi = 10.1055/s-0028-1111126 | s2cid = 71214286 }}</ref>
* 1969: The antiandrogenic activity of spironolactone is discovered<ref name="pmid5344274">{{cite journal | vauthors = Steelman SL, Brooks JR, Morgan ER, Patanelli DJ | title = Anti-androgenic activity of spironolactone | journal = Steroids | volume = 14 | issue = 4 | pages = 449–50 | year = 1969 | pmid = 5344274 | doi = 10.1016/s0039-128x(69)80007-3}}</ref>
* 1972: The antiandrogenic activity of flutamide is first reported<ref name="pmid4264731">{{cite journal | vauthors = Neri R, Florance K, Koziol P, Van Cleave S | title = A biological profile of a nonsteroidal antiandrogen, SCH 13521 (4'-nitro-3'trifluoromethylisobutyranilide) | journal = Endocrinology | volume = 91 | issue = 2 | pages = 427–37 | date = August 1972 | pmid = 4264731 | doi = 10.1210/endo-91-2-427 }}</ref><ref name="pmid4116667">{{cite journal | vauthors = Neri RO, Monahan M | title = Effects of a novel nonsteroidal antiandrogen on canine prostatic hyperplasia | journal = Invest Urol | volume = 10 | issue = 2 | pages = 123–30 | date = September 1972 | pmid = 4116667 }}</ref>
* 1973: Cyproterone acetate was first introduced for medical use, to treat sexual deviance<ref name="pmid8005205">{{cite journal | vauthors = Neumann F | title = The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research | journal = Exp. Clin. Endocrinol. | volume = 102 | issue = 1 | pages = 1–32 | date = 1994 | pmid = 8005205 | doi = 10.1055/s-0029-1211261 | doi-access = free }}</ref>
* 1977: The first-generation antiandrogen nilutamide is first described<ref name="pmid385986">{{cite journal | vauthors = Raynaud JP, Bonne C, Bouton MM, Lagace L, Labrie F | title = Action of a non-steroid anti-androgen, RU 23908, in peripheral and central tissues | journal = J. Steroid Biochem. | volume = 11 | issue = 1A | pages = 93–9 | year = 1979 | pmid = 385986 | doi = 10.1016/0022-4731(79)90281-4}}</ref>
* 1978: Spironolactone is first studied in the treatment of hirsutism in women<ref name="pmid6205409"/><ref name="pmid717935">{{cite journal | vauthors = Ober KP, Hennessy JF | title = Spironolactone therapy for hirsutism in a hyperandrogenic woman | journal = Ann. Intern. Med. | volume = 89 | issue = 5 Pt 1 | pages = 643–4 | year = 1978 | pmid = 717935 | doi = 10.7326/0003-4819-89-5-643}}</ref>
* 1979: Combined androgen blockade is first studied<ref name="pmid16631454">{{cite journal | vauthors = Klotz L | title = Combined androgen blockade: an update | journal = Urol. Clin. North Am. | volume = 33 | issue = 2 | pages = 161–6, v–vi | date = May 2006 | pmid = 16631454 | doi = 10.1016/j.ucl.2005.12.001 }}</ref><ref name="pmid6819101">{{cite journal | vauthors = Labrie F, Dupont A, Belanger A, Cusan L, Lacourciere Y, Monfette G, Laberge JG, Emond JP, Fazekas AT, Raynaud JP, Husson JM | title = New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen | journal = Clin Invest Med | volume = 5 | issue = 4 | pages = 267–75 | date = 1982 | pmid = 6819101 }}</ref>
* 1980: Medical castration via a GnRH analogue is first achieved{{Citation needed|date=March 2020}}
* 1982: The first-generation antiandrogen bicalutamide is first described<ref name="EngelKleemann2014">{{cite book | vauthors = Engel J, Kleemann A, Kutscher B, Reichert D |title=Pharmaceutical Substances: Syntheses, Patents and Applications of the most relevant APIs |edition=5th |year=2009 |url=https://books.google.com/books?id=4lCGAwAAQBAJ&pg=PA153 |publisher=Thieme |isbn=978-3-13-179275-4 |pages=153–154}}</ref>
* 1982: Combined androgen blockade for prostate cancer is developed
* 1983: Flutamide is first introduced, in Chile, for medical use, to treat prostate cancer<ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1695|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=1695–|access-date=2 January 2019|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112173105/https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1695|url-status=live}}</ref><ref name="Ireland2013">{{cite book|title=The Irish Reports: Containing Reports of Cases Argued and Determined in the Court of Appeal, the High Court of Justice, the Court of Bankruptcy, in Ireland, and the Irish Land Commission|url=https://books.google.com/books?id=FQhMAQAAIAAJ|year=1990|publisher=Incorporated Council of Law Reporting for Ireland|pages=501–502|access-date=2019-01-02|archive-date=2023-01-12|archive-url=https://web.archive.org/web/20230112173103/https://books.google.com/books?id=FQhMAQAAIAAJ|url-status=live}}</ref>
* 1987: Nilutamide is first introduced, in France, for medical use, to treat prostate cancer<ref name="BéguéBonnet-Delpon2008"/>
* 1989: Combined androgen blockade via flutamide and a GnRH analogue is found to be superior to a GnRH analogue alone for prostate cancer
* 1989: Flutamide is first introduced for medical use in the United States, to treat prostate cancer<ref name="Regitz-Zagrosek2012">{{cite book| vauthors = Regitz-Zagrosek V |title=Sex and Gender Differences in Pharmacology |url= https://books.google.com/books?id=J3VxihGDh9wC&pg=PA575| date=2 October 2012 |publisher=Springer Science & Business Media|isbn=978-3-642-30725-6|pages=575–}}</ref>
* 1989: Flutamide is first studied in the treatment of hirsutism in women<ref name="pmid2147859"/>
* 1992: The androgen synthesis inhibitor abiraterone acetate is first described<ref name="ICR2014">{{Cite web|url=https://www.icr.ac.uk/news-features/latest-features/abiraterone-a-story-of-scientific-innovation-and-commercial-partnership|title=Abiraterone: A story of scientific innovation and commercial partnership - the Institute of Cancer Research, London|access-date=2019-01-02|archive-date=2019-01-01|archive-url=https://web.archive.org/web/20190101101202/https://www.icr.ac.uk/news-features/latest-features/abiraterone-a-story-of-scientific-innovation-and-commercial-partnership|url-status=live}}</ref>
* 1995: Bicalutamide is first introduced for medical use, to treat prostate cancer<ref name="BéguéBonnet-Delpon2008" />
* 1996: Nilutamide is first introduced for medical use in the United States, to treat prostate cancer<ref name="AdisInsight-Nilutamide">{{Cite web | url = http://adisinsight.springer.com/drugs/800004379 | title = Nilutamide | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2019-01-02 | archive-date = 2021-05-05 | archive-url = https://web.archive.org/web/20210505173834/https://adisinsight.springer.com/drugs/800004379 | url-status = live }}</ref>
* 2006: The second-generation nonsteroidal antiandrogen enzalutamide is first described<ref name="US20070004753">Sawyers, C., Jung, M., Chen, C., Ouk, S., Welsbie, D., Tran, C., ... & Yoo, D. (2006). U.S. Patent Application No. 11/433,829. https://patents.google.com/patent/US20070004753 [https://patents.google.com/patent/US20070004753]</ref>
* 2007: The second-generation nonsteroidal antiandrogen apalutamide is first described<ref name="WO2007126765">{{Cite web|url=https://worldwide.espacenet.com/publicationDetails/originalDocument?FT=D&date=20071108&DB=EPODOC&locale=en_EP&CC=WO&NR=2007126765A2&KC=A2&ND=6|title=Espacenet - Original document|access-date=2019-01-02|archive-date=2021-11-04|archive-url=https://web.archive.org/web/20211104133256/https://worldwide.espacenet.com/publicationDetails/originalDocument?FT=D&date=20071108&DB=EPODOC&locale=en_EP&CC=WO&NR=2007126765A2&KC=A2&ND=6|url-status=live}}</ref>
* 2011: Abiraterone acetate is first introduced for medical use, to treat prostate cancer<ref name="AdisInsight-Abiraterone-Acetate">{{Cite web|url=https://adisinsight.springer.com/drugs/800005133|title=Abiraterone acetate - Johnson & Johnson|work=AdisInsight|publisher=Springer Nature Switzerland AG|access-date=2019-01-02|archive-date=2019-01-03|archive-url=https://web.archive.org/web/20190103055744/https://adisinsight.springer.com/drugs/800005133|url-status=live}}</ref>
* 2012: Enzalutamide is first introduced for medical use, to treat prostate cancer<ref name="AdisInsight-Enzalutamide">{{Cite web | url = https://adisinsight.springer.com/drugs/800026688 | title = Enzalutamide - Astellas Pharma/Medivation | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2019-01-02 | archive-date = 2018-07-17 | archive-url = https://web.archive.org/web/20180717212735/https://adisinsight.springer.com/drugs/800026688 | url-status = live }}</ref>
* 2018: Apalutamide is first introduced for medical use, to treat prostate cancer<ref name="AdisInsight-Apalutamide">{{Cite web | url = http://adisinsight.springer.com/drugs/800032695 | title = Apalutamide - Janssen Research and Development | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2019-01-02 | archive-date = 2019-01-03 | archive-url = https://web.archive.org/web/20190103110524/https://adisinsight.springer.com/drugs/800032695 | url-status = live }}</ref>
* 2018: Elagolix is the first orally active GnRH antagonist to be introduced for medical use<ref name="AdisInsight-Elagolix" />
* 2019: Relugolix is the second orally active GnRH antagonist to be introduced for medical use<ref name="AdisInsight-Relugolix">{{Cite web | url = https://adisinsight.springer.com/drugs/800028257 | title = Relugolix - Myovant/Takeda | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2021-08-19 | archive-date = 2021-08-19 | archive-url = https://web.archive.org/web/20210819053135/https://adisinsight.springer.com/drugs/800028257 | url-status = live }}</ref>
* 2019: Darolutamide is first introduced for medical use, to treat prostate cancer<ref name="AdisInsight-Darolutamide">{{cite web | title=Darolutamide - Bayer HealthCare/Orion | website=AdisInsight | date=21 January 2025 | url=https://adisinsight.springer.com/drugs/800033671 | access-date=8 May 2025}}</ref>