Editing Antiandrogen (section)

====Prostate cancer====
{{See also|Management of prostate cancer#Hormonal therapy|Androgen deprivation therapy}}

Androgens like testosterone and particularly DHT are importantly involved in the development and progression of prostate cancer.<ref name="pmid27019626">{{cite journal | vauthors = Wadosky KM, Koochekpour S | title = Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer | journal = Int. J. Biol. Sci. | volume = 12 | issue = 4 | pages = 409–26 | year = 2016 | pmid = 27019626 | pmc = 4807161 | doi = 10.7150/ijbs.14090 }}</ref> They act as [[growth factor]]s in the [[prostate gland]], stimulating [[cell division]] and [[tissue growth]].<ref name="pmid27019626" /> In accordance, therapeutic modalities that reduce androgen signaling in the prostate gland, referred to collectively as [[androgen deprivation therapy]], are able to significantly slow the course of prostate cancer and extend life in men with the disease.<ref name="pmid27019626" /> Although antiandrogens are effective in slowing the progression of prostate cancer, they are not generally curative, and with time, the disease adapts and androgen deprivation therapy eventually becomes ineffective.<ref name="pmid21680543">{{cite journal | vauthors = Massard C, Fizazi K | title = Targeting continued androgen receptor signaling in prostate cancer | journal = Clin. Cancer Res. | volume = 17 | issue = 12 | pages = 3876–83 | year = 2011 | pmid = 21680543 | doi = 10.1158/1078-0432.CCR-10-2815 | doi-access = free }}</ref> When this occurs, other treatment approaches, such as [[chemotherapy]], may be considered.<ref name="pmid21680543" />

The most common methods of androgen deprivation therapy currently employed to treat prostate cancer are [[castration]] (with a GnRH modulator or [[orchiectomy]]), nonsteroidal antiandrogens, and the androgen synthesis inhibitor [[abiraterone acetate]].<ref name="pmid27019626" /> Castration may be used alone or in combination with one of the other two treatments.<ref name="pmid27019626" /><ref name="pmid17604502">{{cite journal | vauthors = Msaouel P, Diamanti E, Tzanela M, Koutsilieris M | title = Luteinising hormone-releasing hormone antagonists in prostate cancer therapy | journal = Expert Opin Emerg Drugs | volume = 12 | issue = 2 | pages = 285–99 | year = 2007 | pmid = 17604502 | doi = 10.1517/14728214.12.2.285 | s2cid = 41988320 }}</ref> When castration is combined with a nonsteroidal antiandrogen like [[bicalutamide]], this strategy is referred to as [[combined androgen blockade]] (also known as complete or maximal androgen blockade).<ref name="pmid27019626" /><ref name="pmid21091846">{{Cite journal | vauthors = Akaza H | title = Combined androgen blockade for prostate cancer: review of efficacy, safety, and cost-effectiveness | journal = Cancer Science | volume = 102 | pages = 51–6 |date=Jan 2011 | pmid = 21091846 | doi = 10.1111/j.1349-7006.2010.01774.x | issue = 1| s2cid = 38486547 | doi-access = free }}</ref> [[Enzalutamide]], [[apalutamide]], and abiraterone acetate are specifically approved for use in combination with castration to treat castration-resistant prostate cancer.<ref name="pmid27019626" /><ref name="pmid24390422">{{cite journal | vauthors = Mateo J, Smith A, Ong M, de Bono JS | title = Novel drugs targeting the androgen receptor pathway in prostate cancer | journal = Cancer Metastasis Rev. | volume = 33 | issue = 2–3 | pages = 567–79 | year = 2014 | pmid = 24390422 | doi = 10.1007/s10555-013-9472-2 | s2cid = 13980764 }}</ref> Monotherapy with the nonsteroidal antiandrogen bicalutamide is also used in the treatment of prostate cancer as an alternative to castration with comparable effectiveness but with a different and potentially advantageous side effect profile.<ref name="pmid27019626" /><ref name="pmid11121992" /><ref name="pmid11502439">{{cite journal |vauthors=Kolvenbag GJ, Iversen P, Newling DW | title = Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer | journal = Urology | volume = 58 | issue = 2 Suppl 1 | pages = 16–23 |date=August 2001 | pmid = 11502439 | doi = 10.1016/s0090-4295(01)01237-7}}</ref>

[[High-dose estrogen]] was the first functional antiandrogen used to treat prostate cancer. It was widely used, but has largely been abandoned for this indication in favor of newer agents with improved safety profiles and fewer feminizing side effects.<ref name="pmid12667881">{{cite journal | vauthors = Mcleod DG | title = Hormonal therapy: historical perspective to future directions | journal = Urology | volume = 61 | issue = 2 Suppl 1 | pages = 3–7 | year = 2003 | pmid = 12667881 | doi = 10.1016/s0090-4295(02)02393-2 }}</ref> [[Cyproterone acetate]] was developed subsequently to high-dose estrogen and is the only steroidal antiandrogen that has been widely used in the treatment of prostate cancer,<ref name="SmithWilliams2005">{{cite book | vauthors = Smith HJ, Williams H | title = Smith and Williams' Introduction to the Principles of Drug Design and Action, Fourth Edition |url=https://books.google.com/books?id=P2W6B9FQRKsC&pg=PA489 |date=10 October 2005 |publisher=CRC Press |isbn=978-0-203-30415-0 |pages=489–}}</ref> but it has largely been replaced by nonsteroidal antiandrogens, which are newer and have greater effectiveness, tolerability, and safety.<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=PA680|date=8 November 2010|publisher=Lippincott Williams & Wilkins|isbn=978-1-60547-431-1|pages=679–680|quote=From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used.|access-date=27 December 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224032/https://books.google.com/books?id=WL4arNFsQa8C&pg=PA680|url-status=live}}</ref><ref name="KaliksDel Giglio2008">{{cite journal | vauthors = Kaliks RA, Del Giglio A | title = Management of advanced prostate cancer | journal = Revista da Associação Médica Brasileira | volume = 54 | issue = 2 | pages = 178–82 | year = 2008 | pmid = 18506331 | doi = 10.1590/S0104-42302008000200025 | url = http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf | doi-access = free | access-date = 2016-12-27 | archive-date = 2017-05-10 | archive-url = https://web.archive.org/web/20170510112152/http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf | url-status = live }}</ref> Bicalutamide, as well as enzalutamide, have largely replaced the earlier nonsteroidal antiandrogens [[flutamide]] and [[nilutamide]], which are now little used.<ref name="pmid21091846" /><ref name="HHS2010">{{citation | title = Bicalutamide BPCA Drug Use Review in the Pediatric Population | vauthors = Chang S | publisher = [[United States Department of Health and Human Services|U.S. Department of Health and Human Service]] | date = 10 March 2010 | access-date = 20 July 2016 | url = https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM214400.pdf | archive-date = 24 October 2016 | archive-url = https://web.archive.org/web/20161024181831/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM214400.pdf | url-status = live }}</ref><ref name="Gulley2011">{{cite book | vauthors = Gulley JL |title=Prostate Cancer |url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PT81 |year=2011 |publisher=Demos Medical Publishing |isbn=978-1-935281-91-7 |pages=81–}}</ref><ref name="Moser2008">{{cite book |vauthors=Lutz M |title=Controversies in the Treatment of Prostate Cancer |url=https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41 |date=1 January 2008 |publisher=Karger Medical and Scientific Publishers |isbn=978-3-8055-8524-8 |pages=41–42 |access-date=27 December 2016 |archive-date=12 January 2023 |archive-url=https://web.archive.org/web/20230112173054/https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41 |url-status=live }}</ref><ref name="Demnos2011">{{cite book |title=Prostate Cancer |url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PA505 |date=20 December 2011 |publisher=Demos Medical Publishing |isbn=978-1-935281-91-7 |pages=505–}}</ref> The earlier androgen synthesis inhibitors [[aminoglutethimide]] and [[ketoconazole]] have only limitedly been used in the treatment of prostate cancer due to [[toxicity]] concerns and have been replaced by abiraterone acetate.<ref name="FiggChau2010" />

In addition to active treatment of prostate cancer, antiandrogens are effective as [[prophylaxis]] (preventatives) in reducing the risk of ever developing prostate cancer.<ref name="pmid21604953">{{cite journal | vauthors = Rittmaster RS | title = Chemoprevention of prostate cancer | journal = Acta Oncol | volume = 50 | issue = Suppl 1 | pages = 127–36 | year = 2011 | pmid = 21604953 | doi = 10.3109/0284186X.2010.527367 | doi-access = free }}</ref> Antiandrogens have only limitedly been assessed for this purpose, but the 5α-reductase inhibitors [[finasteride]] and [[dutasteride]] and the steroidal AR antagonist [[spironolactone]] have been associated with significantly reduced risk of prostate cancer.<ref name="pmid21604953" /><ref name="pmid27735065">{{cite journal | vauthors = Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM | title = Spironolactone use and risk of incident cancers: a retrospective, matched cohort study | journal = Br J Clin Pharmacol | volume = 83| issue = 3| pages = 653–663| year = 2016 | pmid = 27735065 | doi = 10.1111/bcp.13152 | pmc = 5306481 }}</ref> In addition, it is notable that prostate cancer is extremely rare in transgender women who have been on feminizing hormone therapy for an extended period of time.<ref name="pmid19509099">{{cite journal | vauthors = Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ, Spack NP, Tangpricha V, Montori VM | title = Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline | journal = J. Clin. Endocrinol. Metab. | volume = 94 | issue = 9 | pages = 3132–54 | year = 2009 | pmid = 19509099 | doi = 10.1210/jc.2009-0345 | doi-access = free }}</ref><ref name="pmid24329588">{{cite journal | vauthors = Gooren L, Morgentaler A | title = Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens | journal = Andrologia | volume = 46 | issue = 10 | pages = 1156–60 | year = 2014 | pmid = 24329588 | doi = 10.1111/and.12208 | s2cid = 1445627 | doi-access = free }}</ref><ref name="pmid24032068">{{cite journal | vauthors = Turo R, Jallad S, Prescott S, Cross WR | title = Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy | journal = Can Urol Assoc J | volume = 7 | issue = 7–8 | pages = E544–6 | year = 2013 | pmid = 24032068 | pmc = 3758950 | doi = 10.5489/cuaj.175 }}</ref>