Antiandrogen#Medical uses

Antiandrogens are used in the treatment of an assortment of androgen-dependent conditions in both males and females.{{cite journal | vauthors = Sciarra F, Toscano V, Concolino G, Di Silverio F | title = Antiandrogens: clinical applications | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 37 | issue = 3 | pages = 349–362 | date = November 1990 | pmid = 2147859 | doi = 10.1016/0960-0760(90)90484-3 | s2cid = 20274398 }} They are used to treat men with prostate cancer, benign prostatic hyperplasia, pattern hair loss, hypersexuality, paraphilias, and priapism, as well as boys with precocious puberty.{{cite journal | vauthors = Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R | title = Priapism: pathogenesis, epidemiology, and management | journal = The Journal of Sexual Medicine | volume = 7 | issue = 1 Pt 2 | pages = 476–500 | date = January 2010 | pmid = 20092449 | doi = 10.1111/j.1743-6109.2009.01625.x }}{{cite book| vauthors = Steinberg MH, Forget BG, Higgs DR, Weatherall DJ |title=Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management|url=https://books.google.com/books?id=5UcgAwAAQBAJ&pg=PA476|date=17 August 2009|publisher=Cambridge University Press|isbn=978-1-139-48080-2|pages=476–}} In women and girls, antiandrogens are used to treat acne, seborrhea, hidradenitis suppurativa, hirsutism, and hyperandrogenism.{{cite journal | vauthors = Essah PA, Wickham EP, Nunley JR, Nestler JE | title = Dermatology of androgen-related disorders | journal = Clinics in Dermatology | volume = 24 | issue = 4 | pages = 289–298 | year = 2006 | pmid = 16828411 | doi = 10.1016/j.clindermatol.2006.04.004 }}{{cite journal| vauthors = Rabe T, Grunwald K, Feldmann K, Runnebaum B |title=Treatment of hyperandrogenism in women|journal=Gynecological Endocrinology|volume=10|issue=sup3|year=2009|pages=1–44|issn=0951-3590|doi=10.3109/09513599609045658}} Antiandrogens are also used in transgender women as a component of feminizing hormone therapy and as puberty blockers in transgender girls.

{{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.{{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 }} They act as growth factors in the prostate gland, stimulating cell division and tissue growth. 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. 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.{{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 }} When this occurs, other treatment approaches, such as chemotherapy, may be considered.

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. Castration may be used alone or in combination with one of the other two treatments.{{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 }} 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).{{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 }} Enzalutamide, apalutamide, and abiraterone acetate are specifically approved for use in combination with castration to treat castration-resistant prostate cancer.{{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 }} 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.{{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}}

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.{{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 }} 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,{{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–}} but it has largely been replaced by nonsteroidal antiandrogens, which are newer and have greater effectiveness, tolerability, and safety.{{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}}{{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 }} Bicalutamide, as well as enzalutamide, have largely replaced the earlier nonsteroidal antiandrogens flutamide and nilutamide, which are now little used.{{citation | title = Bicalutamide BPCA Drug Use Review in the Pediatric Population | vauthors = Chang S | publisher = 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 = dead }}{{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–}}{{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 }}{{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–}} 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.

In addition to active treatment of prostate cancer, antiandrogens are effective as prophylaxis (preventatives) in reducing the risk of ever developing prostate cancer.{{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 }} 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.{{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 }} 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.{{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 }}{{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 }}{{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 }}

{{See also|Benign prostatic hyperplasia#5α-Reductase inhibitors}}

The 5α-reductase inhibitors finasteride and dutasteride are used to treat benign prostatic hyperplasia, a condition in which the prostate becomes enlarged and this results in urinary obstruction and discomfort.{{cite journal | vauthors = Dörsam J, Altwein J | title = 5alpha-Reductase inhibitor treatment of prostatic diseases: background and practical implications | journal = Prostate Cancer Prostatic Dis. | volume = 12 | issue = 2 | pages = 130–6 | year = 2009 | pmid = 19030020 | doi = 10.1038/pcan.2008.56 | doi-access = free }} They are effective because androgens act as growth factors in the prostate gland. The antiandrogens chlormadinone acetate and oxendolone and the functional antiandrogens allylestrenol and gestonorone caproate are also approved in some countries for the treatment of benign prostatic hyperplasia.{{cite journal | vauthors = Ishizuka O, Nishizawa O, Hirao Y, Ohshima S | title = Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy | journal = Int. J. Urol. | volume = 9 | issue = 11 | pages = 607–12 | year = 2002 | pmid = 12534901 | doi = 10.1046/j.1442-2042.2002.00539.x| s2cid = 8249363 | doi-access = free }}{{cite book| vauthors = Raspé G, Brosig W |title=International Symposium on the Treatment of Carcinoma of the Prostate, Berlin, November 13 to 15, 1969: Life Science Monographs|url=https://books.google.com/books?id=8RjLBAAAQBAJ&pg=PA165|date=22 October 2013|publisher=Elsevier|isbn=978-1-4831-8711-2|pages=165–}}

{{See also|Management of hair loss#Antiandrogens}}

5α-Reductase inhibitors like finasteride, dutasteride, and alfatradiol and the topical nonsteroidal AR antagonist topilutamide (fluridil) are approved for the treatment of pattern hair loss, also known as scalp hair loss or baldness.{{cite book| vauthors = Trüeb RM, Lee WS |title=Male Alopecia: Guide to Successful Management|url=https://books.google.com/books?id=0ue5BAAAQBAJ&pg=PA93|date=13 February 2014|publisher=Springer Science & Business Media|isbn=978-3-319-03233-7|pages=91–93}} This condition is generally caused by androgens, so antiandrogens can slow or halt its progression.{{cite book| vauthors = Bolognia JL, Jorizzo JL, Rapini RP |title=Dermatology|year=2003 |url=https://books.google.com/books?id=f2IwYiyh3YUC&pg=PT1072|publisher=Gulf Professional Publishing|isbn=9789997638991|pages=1072–}} Systemic antiandrogens besides 5α-reductase inhibitors are not generally used to treat scalp hair loss in males due to risks like feminization (e.g., gynecomastia) and sexual dysfunction.{{cite book| vauthors = Simpson NB |title=Pharmacology of the Skin II|volume=87 / 2|year=1989|pages=495–508|issn=0171-2004|doi=10.1007/978-3-642-74054-1_37|series=Handbook of Experimental Pharmacology|isbn=978-3-642-74056-5|chapter=The Effect of Drugs on Hair|publisher=Springer }}{{cite book| vauthors = Unger WP |chapter=Androgenetic alopecia and its treatment. A historical overview|pages=1–33|title=Hair Transplantation | edition =Third |url=https://books.google.com/books?id=_KxsAAAAMAAJ|date=1 February 1995|publisher=Taylor & Francis|isbn=978-0-8247-9363-0}}{{cite journal | vauthors = Giltay EJ, Gooren LJ | title = Potential side effects of androgen deprivation treatment in sex offenders | journal = The Journal of the American Academy of Psychiatry and the Law | volume = 37 | issue = 1 | pages = 53–58 | date = 2009 | pmid = 19297634 }}{{cite book| vauthors = Lam SM, Hempstead BR, Williams EF |title=Aesthetic Medicine|chapter=Medical Management Options for Hair Loss|year=2012|pages=529–535|publisher=Springer |doi=10.1007/978-3-642-20113-4_41|isbn=978-3-642-20112-7}} However, they have been assessed and reported to be effective for this indication.{{cite journal | vauthors = Coskey RJ | title = Dermatologic therapy: December, 1982, through November, 1983 | journal = Journal of the American Academy of Dermatology | volume = 11 | issue = 1 | pages = 25–52 | date = July 1984 | pmid = 6376557 | doi = 10.1016/S0190-9622(84)80163-2 }}

Systemic antiandrogens are generally not used to treat acne in males due to their high risk of feminization (e.g., gynecomastia) and sexual dysfunction.{{cite book| vauthors = Plewig G, Kligman AM |title= ACNE and ROSACEA|url=https://books.google.com/books?id=0cD-CAAAQBAJ&pg=PA687|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-59715-2|pages=687–}}{{cite book| vauthors = Alldredge BK, Corelli RL, Ernst ME |title=Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs|url=https://books.google.com/books?id=qcVpuHngXK0C&pg=PA952|date=1 February 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-713-7|pages=952–}} However, they have been studied for acne in males and found to be effective.{{cite journal | vauthors = Ward A, Brogden RN, Heel RC, Speight TM, Avery GS | title = Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders | journal = Drugs | volume = 28 | issue = 1 | pages = 6–37 | date = July 1984 | pmid = 6235105 | doi = 10.2165/00003495-198428010-00002 }}{{cite book| vauthors = Rasmusson GH |title= Chapter 18. Chemical Control of Androgen Action|volume=21|year=1986|pages=179–188|issn=0065-7743|doi=10.1016/S0065-7743(08)61128-8|series=Annual Reports in Medicinal Chemistry|publisher= Academic Press|isbn=9780120405213}}{{cite journal| vauthors = Cormane RH, van der Meeren HL |title=Cyproteronacetate in the management of severe acne in males|journal=Archives of Dermatological Research |volume=271 |issue=2 |year=1981 |pages=183–187 |issn=0340-3696|doi=10.1007/BF00412545|s2cid=12153042}}{{cite journal | vauthors = Misch KJ, Dolman WF, Neild V, Rhodes EL | title = Response of male acne to antiandrogen therapy with cyproterone acetate | journal = Dermatologica | volume = 173 | issue = 3 | pages = 139–142 | date = 1986 | pmid = 2945742 | doi = 10.1159/000249236 }} Clascoterone, a topical antiandrogen, is effective for acne in males, albeit modestly, and has been approved by the FDA in August 2020.{{cite journal | vauthors = Kircik LH | title = What's new in the management of acne vulgaris | journal = Cutis | volume = 104 | issue = 1 | pages = 48–52 | date = July 2019 | pmid = 31487336 | url = https://www.mdedge.com/dermatology/article/204308/acne/whats-new-management-acne-vulgaris | access-date = 2020-03-30 | archive-date = 2020-10-26 | archive-url = https://web.archive.org/web/20201026050003/https://www.mdedge.com/dermatology/article/204308/acne/whats-new-management-acne-vulgaris | url-status = live }}{{cite journal | vauthors = Hassoun LA, Chahal DS, Sivamani RK, Larsen LN | title = The use of hormonal agents in the treatment of acne | journal = Seminars in Cutaneous Medicine and Surgery | volume = 35 | issue = 2 | pages = 68–73 | date = June 2016 | pmid = 27416311 | doi = 10.12788/j.sder.2016.027 | doi-broken-date = 1 November 2024 }}{{Cite web |date=2020-08-28 |title=Cassiopea Receives FDA Approval for Winlevi® (clascoterone cream 1%), First-in-Class Topical Acne Treatment Targeting the Androgen Receptor - Cassiopea |url=https://www.cassiopea.com/2020/08/27/cassiopea-receives-fda-approval-for-winlevi-clascoterone-cream-1-first-in-class-topical-acne-treatment-targeting-the-androgen-receptor/ |access-date=2024-04-15 |archive-url=https://web.archive.org/web/20200828021558/https://www.cassiopea.com/2020/08/27/cassiopea-receives-fda-approval-for-winlevi-clascoterone-cream-1-first-in-class-topical-acne-treatment-targeting-the-androgen-receptor/ |archive-date=2020-08-28 }}{{Cite web |title=Drugs@FDA: FDA-Approved Drugs |url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213433 |archive-url=https://web.archive.org/web/20201019221210/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213433 |url-status=dead |archive-date=October 19, 2020 |access-date=2024-04-15 |website=www.accessdata.fda.gov |language=en}}

{{See also|Paraphilia#Antiandrogens|Chemical castration#Treatment for sex offenders}}

Androgens increase sex drive,{{cite book| vauthors = Jones RE, Lopez KH |title=Human Reproductive Biology|url=https://books.google.com/books?id=M4kEdSnS-pkC&pg=PA77|date=28 September 2013|publisher=Academic Press|isbn=978-0-12-382185-0|pages=77–}} and for this reason, antiandrogens are able to reduce sex drive in men.{{cite journal | vauthors = Bradford JM | title = The neurobiology, neuropharmacology, and pharmacological treatment of the paraphilias and compulsive sexual behaviour | journal = Can J Psychiatry | volume = 46 | issue = 1 | pages = 26–34 | year = 2001 | pmid = 11221487 | doi = 10.1177/070674370104600104| doi-access = free }}{{cite journal | vauthors = Guay DR | title = Drug treatment of paraphilic and nonparaphilic sexual disorders | journal = Clin Ther | volume = 31 | issue = 1 | pages = 1–31 | year = 2009 | pmid = 19243704 | doi = 10.1016/j.clinthera.2009.01.009 }} In accordance, antiandrogens are used in the treatment of conditions such as hypersexuality (excessively high sex drive) and paraphilias (atypical and sometimes societally unacceptable sexual interests) like pedophilia (sexual attraction to children). They have been used to decrease sex drive in sex offenders so as to reduce the likelihood of recidivism (repeat offenses).{{cite book| vauthors = Marshall WL, Laws DR, Barbaree HE |title=Handbook of Sexual Assault: Issues, Theories, and Treatment of the Offender|url=https://books.google.com/books?id=lkf2BwAAQBAJ&pg=PA297|date=21 November 2013|publisher=Springer Science & Business Media|isbn=978-1-4899-0915-2|pages=297–}} Antiandrogens used for these indications include cyproterone acetate, medroxyprogesterone acetate, and GnRH modulators.{{cite book| vauthors = Stunkard AJ, Baum A |title=Eating, Sleeping, and Sex|url=https://books.google.com/books?id=bf-dRU-Ie9EC&pg=PA209 |year=1989|publisher=Psychology Press|isbn=978-0-8058-0280-1|pages=209–}}{{cite book| vauthors = Phenix A, Hoberman HM |title=Sexual Offending: Predisposing Antecedents, Assessments and Management|url=https://books.google.com/books?id=NhEpCwAAQBAJ&pg=PA759|date=7 December 2015|publisher=Springer|isbn=978-1-4939-2416-5|pages=759–}}

Antiandrogens are used to treat precocious puberty in boys.{{cite journal | vauthors = Brito VN, Latronico AC, Arnhold IJ, Mendonça BB | title = Update on the etiology, diagnosis and therapeutic management of sexual precocity | journal = Arq Bras Endocrinol Metabol | volume = 52 | issue = 1 | pages = 18–31 | date = February 2008 | pmid = 18345393 | doi = 10.1590/S0004-27302008000100005 | doi-access = free }}{{cite journal | vauthors = Tindall DJ, Chang CH, Lobl TJ, Cunningham GR | title = Androgen antagonists in androgen target tissues | journal = Pharmacol. Ther. | volume = 24 | issue = 3 | pages = 367–400 | date = 1984 | pmid = 6205409 | doi = 10.1016/0163-7258(84)90010-x}}{{cite journal | vauthors = Namer M | title = Clinical applications of antiandrogens | journal = J. Steroid Biochem. | volume = 31 | issue = 4B | pages = 719–29 | date = October 1988 | pmid = 2462132 | doi = 10.1016/0022-4731(88)90023-4}}{{cite journal | vauthors = Fraser HM, Baird DT | title = Clinical applications of LHRH analogues | journal = Baillière's Clin. Endocrinol. Metab. | volume = 1 | issue = 1 | pages = 43–70 | date = February 1987 | pmid = 3109366 | doi = 10.1016/S0950-351X(87)80052-6}} They work by opposing the effects of androgens and delaying the development of secondary sexual characteristics and onset of changes in sex drive and function until a more appropriate age. Antiandrogens that have been used for this purpose include cyproterone acetate, medroxyprogesterone acetate, GnRH modulators, spironolactone, bicalutamide, and ketoconazole.{{cite journal | vauthors = Laron Z, Kauli R | title = Experience with cyproterone acetate in the treatment of precocious puberty | journal = J. Pediatr. Endocrinol. Metab. | volume = 13 | issue = Suppl 1 | pages = 805–10 | date = July 2000 | pmid = 10969925 | doi = 10.1515/jpem.2000.13.s1.805| s2cid = 25398066 }}{{cite journal | vauthors = Neumann F, Kalmus J | title = Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience | journal = Exp. Clin. Endocrinol. | volume = 98 | issue = 2 | pages = 71–80 | date = 1991 | pmid = 1838080 | doi = 10.1055/s-0029-1211103 }}{{cite journal | vauthors = Holland FJ | title = Gonadotropin-independent precocious puberty | journal = Endocrinol. Metab. Clin. North Am. | volume = 20 | issue = 1 | pages = 191–210 | date = March 1991 | pmid = 1903104 | doi = 10.1016/s0889-8529(18)30288-3}}{{cite journal | vauthors = Reiter EO, Norjavaara E | title = Testotoxicosis: current viewpoint | journal = Pediatr Endocrinol Rev | volume = 3 | issue = 2 | pages = 77–86 | date = December 2005 | pmid = 16361981 }} Spironolactone and bicalutamide require combination with an aromatase inhibitor to prevent the effects of unopposed estrogens, while the others can be used alone.

Antiandrogens are effective in the treatment of recurrent priapism (potentially painful penile erections that last more than four hours).{{cite journal | vauthors = Levey HR, Kutlu O, Bivalacqua TJ | title = Medical management of ischemic stuttering priapism: a contemporary review of the literature | journal = Asian Journal of Andrology | volume = 14 | issue = 1 | pages = 156–63 | year = 2012 | pmid = 22057380 | pmc = 3753435 | doi = 10.1038/aja.2011.114 }}{{cite journal | vauthors = Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R | title = Priapism: pathogenesis, epidemiology, and management | journal = The Journal of Sexual Medicine | volume = 7 | issue = 1 Pt 2 | pages = 476–500 | year = 2010 | pmid = 20092449 | doi = 10.1111/j.1743-6109.2009.01625.x }}{{cite journal | vauthors = Chow K, Payne S | title = The pharmacological management of intermittent priapismic states | journal = BJU International | volume = 102 | issue = 11 | pages = 1515–21 | year = 2008 | pmid = 18793304 | doi = 10.1111/j.1464-410X.2008.07951.x | s2cid = 35399393 | doi-access = free }}{{cite journal | vauthors = Dahm P, Rao DS, Donatucci CF | title = Antiandrogens in the treatment of priapism | journal = Urology | volume = 59 | issue = 1 | pages = 138 | year = 2002 | pmid = 11796309 | doi = 10.1016/S0090-4295(01)01492-3 }}{{cite journal | vauthors = Yuan J, Desouza R, Westney OL, Wang R | title = Insights of priapism mechanism and rationale treatment for recurrent priapism | journal = Asian Journal of Andrology | volume = 10 | issue = 1 | pages = 88–101 | year = 2008 | pmid = 18087648 | doi = 10.1111/j.1745-7262.2008.00314.x | doi-access = free }}

{{See also|Acne vulgaris#Hormonal agents|Seborrhoeic dermatitis#Antiandrogens|Hirsutism#Medications}}

Antiandrogens are used in the treatment of androgen-dependent skin and hair conditions including acne, seborrhea, hidradenitis suppurativa, hirsutism, and pattern hair loss in women. All of these conditions are dependent on androgens, and for this reason, antiandrogens are effective in treating them. The most commonly used antiandrogens for these indications are cyproterone acetate and spironolactone.{{cite book| vauthors = Baran R, Maibach HI |title=Textbook of Cosmetic Dermatology|url=https://books.google.com/books?id=yIVfq5Lpl2EC&pg=PA388|date=1 October 1998|publisher=CRC Press|isbn=978-1-85317-478-0|pages=388–}} Flutamide has also been studied extensively for such uses, but has fallen out of favor due to its association with hepatotoxicity.{{cite book| vauthors = Maibach HI, Gorouhi F |title=Evidence Based Dermatology|url=https://books.google.com/books?id=V2L1MAoGHVkC&pg=PA526|year=2011|publisher=PMPH-USA|isbn=978-1-60795-039-4|pages=526–}} Bicalutamide, which has a relatively minimal risk of hepatotoxicity, has been evaluated for the treatment of hirsutism and found effective similarly to flutamide and may be used instead of it.{{cite book|vauthors=Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B|title=Evidence-Based Dermatology|url=https://books.google.com/books?id=SbsQij5xkfYC&pg=PA529|date=22 January 2009|publisher=John Wiley & Sons|isbn=978-1-4443-0017-8|pages=529–|access-date=27 December 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110085152/https://books.google.com/books?id=SbsQij5xkfYC&pg=PA529|url-status=live}}{{cite journal | vauthors = Erem C | title = Update on idiopathic hirsutism: diagnosis and treatment | journal = Acta Clin Belg | volume = 68 | issue = 4 | pages = 268–74 | year = 2013 | pmid = 24455796 | doi = 10.2143/ACB.3267 | s2cid = 39120534 }} In addition to AR antagonists, oral contraceptives containing ethinylestradiol are effective in treating these conditions, and may be combined with AR antagonists.{{cite book| vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism |url= https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1004 |year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=1004, 1196}}{{cite book| vauthors = Camacho PM, Gharib H, Sizemore GW |title=Evidence-Based Endocrinology |url=https://books.google.com/books?id=TrLaw_CX1i8C&pg=PA199 |year=2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-1091-3 |pages=199–}}

{{See also|Hyperandrogenism#Treatment}}

Hyperandrogenism is a condition in women in which androgen levels are excessively and abnormally high. It is commonly seen in women with PCOS, and also occurs in women with intersex conditions like congenital adrenal hyperplasia. Hyperandrogenism is associated with virilization – that is, the development of masculine secondary sexual characteristics like male-pattern facial and body hair growth (or hirsutism), voice deepening, increased muscle mass and strength, and broadening of the shoulders, among others. Androgen-dependent skin and hair conditions like acne and pattern hair loss may also occur in hyperandrogenism, and menstrual disturbances, like amenorrhea, are commonly seen. Although antiandrogens do not treat the underlying cause of hyperandrogenism (e.g., PCOS), they are able to prevent and reverse its manifestation and effects. As with androgen-dependent skin and hair conditions, the most commonly used antiandrogens in the treatment of hyperandrogenism in women are cyproterone acetate and spironolactone. Other antiandrogens, like bicalutamide, may be used alternatively.

{{See also|Feminizing hormone therapy#Antiandrogens}}

Antiandrogens are used to prevent or reverse masculinization and to facilitate feminization in transgender women and some non-binary transfeminine individuals who are undergoing hormone therapy and who have not undergone sex reassignment surgery or orchiectomy.{{cite journal | vauthors = Bockting W, Coleman E, De Cuypere G | title = Care of transsexual persons | journal = N. Engl. J. Med. | volume = 364 | issue = 26 | pages = 2559–60; author reply 2560 | year = 2011 | pmid = 21714669 | doi = 10.1056/NEJMc1104884 }} Besides estrogens, the main antiandrogens that have been used for this purpose are cyproterone acetate, spironolactone, and GnRH modulators. Nonsteroidal antiandrogens like bicalutamide are also used for this indication.{{cite journal | vauthors = Randolph JF | title = Gender-Affirming Hormone Therapy for Transgender Females | journal = Clin Obstet Gynecol | volume = 61 | issue = 4 | pages = 705–721 | date = December 2018 | pmid = 30256230 | doi = 10.1097/GRF.0000000000000396 | s2cid = 52821192 }} In addition to use in transgender women, antiandrogens, mainly GnRH modulators, are used as puberty blockers to prevent the onset of puberty in transgender girls until they are older and ready to begin hormone therapy.{{cite journal | vauthors = Vance SR, Ehrensaft D, Rosenthal SM | title = Psychological and medical care of gender nonconforming youth | journal = Pediatrics | volume = 134 | issue = 6 | pages = 1184–92 | year = 2014 | pmid = 25404716 | doi = 10.1542/peds.2014-0772 | s2cid = 5743822 | url = http://pediatrics.aappublications.org/content/pediatrics/134/6/1184.full.pdf | access-date = 2018-05-14 | archive-date = 2018-05-15 | archive-url = https://web.archive.org/web/20180515045718/http://pediatrics.aappublications.org/content/pediatrics/134/6/1184.full.pdf | url-status = live }}

{{See also|Steroidal antiandrogen|Nonsteroidal antiandrogen}}

There are several different types of antiandrogens, including the following:

• Androgen receptor antagonists: Drugs that bind directly to and block the AR.{{cite journal | vauthors = Singh SM, Gauthier S, Labrie F | title = Androgen receptor antagonists (antiandrogens): structure-activity relationships | journal = Current Medicinal Chemistry | volume = 7 | issue = 2 | pages = 211–247 | date = February 2000 | pmid = 10637363 | doi = 10.2174/0929867003375371 }}{{cite book| vauthors = Shen HC, Taplin ME, Balk SP |title=Drug Management of Prostate Cancer |chapter=Androgen Receptor Antagonists |year=2010|pages=71–81|publisher=Springer |doi=10.1007/978-1-60327-829-4_6|isbn=978-1-60327-831-7}} These drugs include the steroidal antiandrogens cyproterone acetate, megestrol acetate, chlormadinone acetate, spironolactone, oxendolone, and osaterone acetate (veterinary) and the nonsteroidal antiandrogens flutamide, bicalutamide, nilutamide, topilutamide, enzalutamide, apalutamide, and darolutamide. Aside from cyproterone acetate and chlormadinone acetate, a few other progestins used in oral contraceptives and/or in menopausal HRT including dienogest, drospirenone, medrogestone, nomegestrol acetate, promegestone, and trimegestone also have varying degrees of AR antagonistic activity.{{cite journal | vauthors = Šauer P, Bořík A, Golovko O, Grabic R, Staňová AV, Valentová O, Stará A, Šandová M, Kocour Kroupová H | display-authors = 6 | title = Do progestins contribute to (anti-)androgenic activities in aquatic environments? | journal = Environmental Pollution | volume = 242 | issue = Pt A | pages = 417–425 | date = November 2018 | pmid = 29990947 | doi = 10.1016/j.envpol.2018.06.104 | bibcode = 2018EPoll.242..417S | s2cid = 51622914 }}{{cite journal | vauthors = Raudrant D, Rabe T | title = Progestogens with antiandrogenic properties | journal = Drugs | volume = 63 | issue = 5 | pages = 463–492 | year = 2003 | pmid = 12600226 | doi = 10.2165/00003495-200363050-00003 | s2cid = 28436828 }}{{cite journal | vauthors = Schneider HP | title = Androgens and antiandrogens | journal = Annals of the New York Academy of Sciences | volume = 997 | issue = 1 | pages = 292–306 | date = November 2003 | pmid = 14644837 | doi = 10.1196/annals.1290.033 | s2cid = 8400556 | bibcode = 2003NYASA.997..292S }}
• Androgen synthesis inhibitors: Drugs that directly inhibit the enzymatic biosynthesis of androgens like testosterone and/or DHT.{{cite book| vauthors = Strauss III JF, Barbieri RL |title=Yen and Jaffe's Reproductive Endocrinology|url=https://books.google.com/books?id=KZ95AAAAQBAJ&pg=PA90|date=13 September 2013|publisher=Elsevier Health Sciences|isbn=978-1-4557-2758-2|pages=90–}}{{cite book| vauthors = Figg W, Chau CH, Small EJ |title=Drug Management of Prostate Cancer|url=https://books.google.com/books?id=4KDrjeWA5-UC&pg=PA93|date=14 September 2010|publisher=Springer Science & Business Media|isbn=978-1-60327-829-4|pages=71–72, 75, 91–96}} Examples include the CYP17A1 inhibitors ketoconazole, abiraterone acetate, and seviteronel, the CYP11A1 (P450scc) inhibitor aminoglutethimide, and the 5α-reductase inhibitors finasteride, dutasteride, epristeride, alfatradiol, and saw palmetto extract (Serenoa repens).{{cite journal | vauthors = Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M | title = An overview on 5alpha-reductase inhibitors | journal = Steroids | volume = 75 | issue = 2 | pages = 109–53 | year = 2010 | pmid = 19879888 | doi = 10.1016/j.steroids.2009.10.005 | s2cid = 44363501 }} A number of other antiandrogens, including cyproterone acetate, spironolactone, medrogestone, flutamide, nilutamide, and bifluranol, are also known to weakly inhibit androgen synthesis.
• Antigonadotropins: Drugs that suppress the gonadotropin-releasing hormone (GnRH)-induced release of gonadotropins and consequent activation of gonadal androgen production.{{cite book| vauthors = Farmer PB, Walker JM |title= The Molecular Basis of Cancer|url=https://books.google.com/books?id=Bva8BAAAQBAJ&pg=PA232|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4684-7313-1|pages=232–}} Examples include GnRH modulators like leuprorelin (a GnRH agonist) and cetrorelix (a GnRH antagonist), progestogens like allylestrenol, chlormadinone acetate, cyproterone acetate, gestonorone caproate, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, osaterone acetate (veterinary), and oxendolone,{{cite book| vauthors = Ledger W, Schlaff WD, Vancaillie TG |title=Chronic Pelvic Pain|url=https://books.google.com/books?id=ON-VBQAAQBAJ&pg=PA55|date=11 December 2014|publisher=Cambridge University Press|isbn=978-1-316-21414-5|pages=55–}} and estrogens like estradiol, estradiol esters, ethinylestradiol, conjugated estrogens, and diethylstilbestrol.
• Miscellaneous: Drugs that oppose the effects of androgens by means other than the above. Examples include estrogens, especially oral and synthetic (e.g., ethinylestradiol, diethylstilbestrol), which stimulate sex hormone-binding globulin (SHBG) production in the liver and thereby decrease free and hence bioactive levels of testosterone and DHT; anticorticotropins such as glucocorticoids, which suppress the adrenocorticotropic hormone (ACTH)-induced production of adrenal androgens; and immunogens and vaccines against androstenedione like ovandrotone albumin and androstenedione albumin, which decrease levels of androgens via the generation of antibodies against the androgen and androgen precursor androstenedione (used only in veterinary medicine).

Certain antiandrogens combine multiple of the above mechanisms.{{cite book| vauthors = Hanna L, Crosby T, Macbeth F |title=Practical Clinical Oncology|url=https://books.google.com/books?id=wm_OCgAAQBAJ&pg=PA37|date=19 November 2015|publisher=Cambridge University Press|isbn=978-1-107-68362-4|pages=37–}} An example is the steroidal antiandrogen cyproterone acetate, which is a potent AR antagonist, a potent progestogen and hence antigonadotropin, a weak glucocorticoid and hence anticorticotropin, and a weak androgen synthesis inhibitor.{{cite book| vauthors = Weber GF |title=Molecular Therapies of Cancer|url=https://books.google.com/books?id=dhs_CgAAQBAJ&pg=PA316|date=22 July 2015|publisher=Springer|isbn=978-3-319-13278-5|pages=314, 316}}{{cite journal | vauthors = Mahler C, Verhelst J, Denis L | title = Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer | journal = Clin Pharmacokinet | volume = 34 | issue = 5 | pages = 405–17 | date = May 1998 | pmid = 9592622 | doi = 10.2165/00003088-199834050-00005 | s2cid = 25200595 }}

The side effects of antiandrogens vary depending on the type of antiandrogen – namely whether it is a selective AR antagonist or lowers androgen levels – as well as the presence of off-target activity in the antiandrogen in question.{{cite journal | vauthors = Iversen P, Melezinek I, Schmidt A | title = Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function | journal = BJU Int. | volume = 87 | issue = 1 | pages = 47–56 | year = 2001 | pmid = 11121992 | doi = 10.1046/j.1464-410x.2001.00988.x| s2cid = 28215804 | doi-access = free }}{{cite book|vauthors=Thomas JA|title=Endocrine Toxicology, Second Edition|url=https://books.google.com/books?id=URc5JMoNirgC&pg=PA152|date=12 March 1997|publisher=CRC Press|isbn=978-1-4398-1048-4|pages=152–|access-date=27 December 2016|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111061946/https://books.google.com/books?id=URc5JMoNirgC&pg=PA152|url-status=live}} For instance, whereas antigonadotropic antiandrogens like GnRH modulators and cyproterone acetate are associated with pronounced sexual dysfunction and osteoporosis in men, selective AR antagonists like bicalutamide are not associated with osteoporosis and have been associated with only minimal sexual dysfunction.{{cite journal | vauthors = Anderson J | title = The role of antiandrogen monotherapy in the treatment of prostate cancer | journal = BJU Int. | volume = 91 | issue = 5 | pages = 455–61 | year = 2003 | pmid = 12603397 | doi = 10.1046/j.1464-410x.2003.04026.x| s2cid = 8639102 | doi-access = free }}{{cite book| vauthors = Priestman T |title=Cancer Chemotherapy in Clinical Practice|url=https://books.google.com/books?id=K41Lf91GULcC&pg=PA97|date=26 May 2012|publisher=Springer Science & Business Media|isbn=978-0-85729-727-3|pages=97–}} These differences are thought related to the fact that antigonadotropins suppress androgen levels and by extension levels of bioactive metabolites of androgens like estrogens and neurosteroids whereas selective AR antagonists similarly neutralize the effects of androgens but leave levels of androgens and hence their metabolites intact (and in fact can even increase them as a result of their progonadotropic effects). As another example, the steroidal antiandrogens cyproterone acetate and spironolactone possess off-target actions including progestogenic, antimineralocorticoid, and/or glucocorticoid activity in addition to their antiandrogen activity, and these off-target activities can result in additional side effects.

In males, the major side effects of antiandrogens are demasculinization and feminization.{{cite journal | vauthors = Higano CS | title = Side effects of androgen deprivation therapy: monitoring and minimizing toxicity | journal = Urology | volume = 61 | issue = 2 Suppl 1 | pages = 32–8 | year = 2003 | pmid = 12667885 | doi = 10.1016/S0090-4295(02)02397-X}} These side effects include breast pain/tenderness and gynecomastia (breast development/enlargement), reduced body hair growth/density, decreased muscle mass and strength, feminine changes in fat mass and distribution, and reduced penile length and testicular size. The rates of gynecomastia in men with selective AR antagonist monotherapy have been found to range from 30 to 85%.{{cite journal | vauthors = Di Lorenzo G, Autorino R, Perdonà S, De Placido S | title = Management of gynaecomastia in patients with prostate cancer: a systematic review | journal = Lancet Oncol. | volume = 6 | issue = 12 | pages = 972–9 | date = December 2005 | pmid = 16321765 | doi = 10.1016/S1470-2045(05)70464-2 }} In addition, antiandrogens can cause infertility, osteoporosis, hot flashes, sexual dysfunction (including loss of libido and erectile dysfunction), depression, fatigue, anemia, and decreased semen/ejaculate volume in males.{{failed verification|reason=source does not attribute antiandrogen as the causative agent of all side effects listed.|date=July 2019}} Conversely, the side effects of selective AR antagonists in women are minimal.{{cite book| vauthors = Shapiro J |title=Hair Disorders: Current Concepts in Pathophysiology, Diagnosis and Management, An Issue of Dermatologic Clinics|url=https://books.google.com/books?id=9rLeICotHEoC&pg=PT187|date=12 November 2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-7169-1|pages=187–}} However, antigonadotropic antiandrogens like cyproterone acetate can produce hypoestrogenism, amenorrhea, and osteoporosis in premenopausal women, among other side effects.{{cite book| vauthors = Futterweit W |title=Polycystic Ovarian Disease|url=https://books.google.com/books?id=siSSBgAAQBAJ&pg=PT282|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4613-8289-8|pages=282–}}{{cite journal | vauthors = Katsambas AD, Dessinioti C | title = Hormonal therapy for acne: why not as first line therapy? facts and controversies | journal = Clin. Dermatol. | volume = 28 | issue = 1 | pages = 17–23 | year = 2010 | pmid = 20082945 | doi = 10.1016/j.clindermatol.2009.03.006 }} In addition, androgen receptor antagonists can produce unfavorable effects on cholesterol levels, which long-term may increase the risk of cardiovascular disease.{{cite journal | vauthors = Baldani DP, Skrgatic L, Ougouag R, Kasum M | title = The cardiometabolic effect of current management of polycystic ovary syndrome: strategies of prevention and treatment | journal = Gynecol Endocrinol | volume = 34 | issue = 2 | pages = 87–91 | date = February 2018 | pmid = 28944709 | doi = 10.1080/09513590.2017.1381681 | s2cid = 205631980 | url = }}{{cite journal | vauthors = Nakhjavani M, Hamidi S, Esteghamati A, Abbasi M, Nosratian-Jahromi S, Pasalar P | title = Short term effects of spironolactone on blood lipid profile: a 3-month study on a cohort of young women with hirsutism | journal = Br J Clin Pharmacol | volume = 68 | issue = 4 | pages = 634–7 | date = October 2009 | pmid = 19843067 | pmc = 2780289 | doi = 10.1111/j.1365-2125.2009.03483.x | url = }}{{cite journal | vauthors = Cignarella A, Mioni R, Sabbadin C, Dassie F, Parolin M, Vettor R, Barbot M, Scaroni C | title = Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS | journal = Int J Mol Sci | volume = 21 | issue = 24 | date = December 2020 | page = 9554 | pmid = 33334002 | pmc = 7765466 | doi = 10.3390/ijms21249554 | url = | doi-access = free }}{{cite journal | vauthors = Moretti C, Guccione L, Di Giacinto P, Simonelli I, Exacoustos C, Toscano V, Motta C, De Leo V, Petraglia F, Lenzi A | title = Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and Severe Hirsutism: A Double-Blind Randomized Controlled Trial | journal = J. Clin. Endocrinol. Metab. | volume = 103 | issue = 3 | pages = 824–838 | date = March 2018 | pmid = 29211888 | doi = 10.1210/jc.2017-01186 | doi-access = free }}{{cite journal | last1 = Coleman | first1 = E. | last2 = Radix | first2 = A. E. | last3 = Bouman | first3 = W. P. | last4 = Brown | first4 = G. R. | last5 = de Vries | first5 = A. L. C. | last6 = Deutsch | first6 = M. B. | last7 = Ettner | first7 = R. | last8 = Fraser | first8 = L. | last9 = Goodman | first9 = M. | last10 = Green | first10 = J. | last11 = Hancock | first11 = A. B. | last12 = Johnson | first12 = T. W. | last13 = Karasic | first13 = D. H. | last14 = Knudson | first14 = G. A. | last15 = Leibowitz | first15 = S. F. | last16 = Meyer-Bahlburg | first16 = H. F. L. | last17 = Monstrey | first17 = S. J. | last18 = Motmans | first18 = J. | last19 = Nahata | first19 = L. | last20 = Nieder | first20 = T. O. | last21 = Reisner | first21 = S. L. | last22 = Richards | first22 = C. | last23 = Schechter | first23 = L. 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E. | last78 = Kvach | first78 = E. J. | last79 = Malouf | first79 = M. A. | last80 = Massey | first80 = R. | last81 = Mazur | first81 = T. | last82 = McLachlan | first82 = C. | last83 = Morrison | first83 = S. D. | last84 = Mosser | first84 = S. W. | last85 = Neira | first85 = P. M. | last86 = Nygren | first86 = U. | last87 = Oates | first87 = J. M. | last88 = Obedin-Maliver | first88 = J. | last89 = Pagkalos | first89 = G. | last90 = Patton | first90 = J. | last91 = Phanuphak | first91 = N. | last92 = Rachlin | first92 = K. | last93 = Reed | first93 = T. | last94 = Rider | first94 = G. N. | last95 = Ristori | first95 = J. | last96 = Robbins-Cherry | first96 = S. | last97 = Roberts | first97 = S. A. | last98 = Rodriguez-Wallberg | first98 = K. A. | last99 = Rosenthal | first99 = S. M. | display-authors = 1 | last100 = Sabir | first100 = K. | last101 = Safer | first101 = J. D. | last102 = Scheim | first102 = A. I. | last103 = Seal | first103 = L. J. | last104 = Sehoole | first104 = T. J. | last105 = Spencer | first105 = K. | last106 = St. Amand | first106 = C. | last107 = Steensma | first107 = T. D. | last108 = Strang | first108 = J. F. | last109 = Taylor | first109 = G. B. | last110 = Tilleman | first110 = K. | last111 = T’Sjoen | first111 = G. G. | last112 = Vala | first112 = L. N. | last113 = Van Mello | first113 = N. M. | last114 = Veale | first114 = J. F. | last115 = Vencill | first115 = J. A. | last116 = Vincent | first116 = B. | last117 = Wesp | first117 = L. M. | last118 = West | first118 = M. A. | last119 = Arcelus | first119 = J. | title = Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 | journal = International Journal of Transgender Health | date = 19 August 2022 | volume = 23 | issue = Suppl 1 | pages = S1–S259 | issn = 2689-5269 | doi = 10.1080/26895269.2022.2100644 | doi-access=free | pmid = 36238954 | pmc = 9553112 | url = }}{{cite journal | vauthors = Godsland IF, Wynn V, Crook D, Miller NE | title = Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions | journal = American Heart Journal | volume = 114 | issue = 6 | pages = 1467–1503 | date = December 1987 | pmid = 3318361 | doi = 10.1016/0002-8703(87)90552-7 }}{{cite journal | vauthors = Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Sperling L, Virani SS, Yeboah J | title = 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines | journal = Circulation | volume = 139 | issue = 25 | pages = e1082–e1143 | date = June 2019 | pmid = 30586774 | pmc = 7403606 | doi = 10.1161/CIR.0000000000000625 | url = }}

A number of antiandrogens have been associated with hepatotoxicity.{{cite journal | vauthors = Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A | title = Hepatotoxicity induced by antiandrogens: a review of the literature | journal = Urol. Int. | volume = 73 | issue = 4 | pages = 289–95 | year = 2004 | pmid = 15604569 | doi = 10.1159/000081585 | s2cid = 24799765 }} These include, to varying extents, cyproterone acetate, flutamide, nilutamide, bicalutamide, aminoglutethimide, and ketoconazole. In contrast, spironolactone, enzalutamide,{{cite journal | vauthors = Keating GM | title = Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer | journal = Drugs & Aging | volume = 32 | issue = 3 | pages = 243–9 | date = March 2015 | pmid = 25711765 | doi = 10.1007/s40266-015-0248-y | s2cid = 29563345 }} and other antiandrogens are not associated with significant rates of hepatotoxicity. However, although they do not pose a risk of hepatotoxicity, spironolactone has a risk of hyperkalemia and enzalutamide has a risk of seizures.{{citation needed|date=May 2021}}

In women who are pregnant, antiandrogens can interfere with the androgen-mediated sexual differentiation of the genitalia and brain of male fetuses.{{cite book| vauthors = Leppert PC, Peipert JF |title=Primary Care for Women|url=https://books.google.com/books?id=PiiD0iUNhlIC&pg=PA277|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-3790-6|pages=277–}} This manifests primarily as ambiguous genitalia – that is, undervirilized or feminized genitalia, which, anatomically, are a cross between a penis and a vagina – and theoretically also as femininity.{{cite book|vauthors=Rathus SA, Nevid JS, Fichner-Rathus L|title=Human sexuality in a world of diversity|url=https://books.google.com/books?id=HahZAAAAYAAJ|year=2005|publisher=Pearson Allyn and Bacon|isbn=978-0-205-40615-9|page=313|access-date=2016-12-27|archive-date=2023-02-26|archive-url=https://web.archive.org/web/20230226052955/https://books.google.com/books?id=HahZAAAAYAAJ|url-status=live}} As such, antiandrogens are teratogens, and women who are pregnant should not be treated with an antiandrogen. Moreover, women who can or may become pregnant are strongly recommended to take an antiandrogen only in combination with proper contraception.

Antiandrogens are relatively safe in acute overdose.{{Citation needed|date=July 2018}}

Inhibitors and inducers of cytochrome P450 enzymes may interact with various antiandrogens.{{Citation needed|date=July 2018}}

{{Relative potencies of selected antiandrogens in rats}}

AR antagonists act by directly binding to and competitively displacing androgens like testosterone and DHT from the AR, thereby preventing them from activating the receptor and mediating their biological effects. AR antagonists are classified into two types, based on chemical structure: steroidal and nonsteroidal.{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1372|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=228–231, 1371–1372}} Steroidal AR antagonists are structurally related to steroid hormones like testosterone and progesterone, whereas nonsteroidal AR antagonists are not steroids and are structurally distinct. Steroidal AR antagonists tend to have off-target hormonal actions due to their structural similarity to other steroid hormones. In contrast, nonsteroidal AR antagonists are selective for the AR and have no off-target hormonal activity. For this reason, they are sometimes described as "pure" antiandrogens.

Although they are described as antiandrogens and indeed show only such effects generally, most or all steroidal AR antagonists are actually not silent antagonists of the AR but rather are weak partial agonists and are able to activate the receptor in the absence of more potent AR agonists like testosterone and DHT.{{cite journal | vauthors = Poyet P, Labrie F | title = Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate | journal = Molecular and Cellular Endocrinology | volume = 42 | issue = 3 | pages = 283–8 | date = October 1985 | pmid = 3930312 | doi = 10.1016/0303-7207(85)90059-0 | s2cid = 24746807 }}{{cite journal | vauthors = Luthy IA, Begin DJ, Labrie F | title = Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture | journal = Journal of Steroid Biochemistry | volume = 31 | issue = 5 | pages = 845–52 | year = 1988 | pmid = 2462135 | doi = 10.1016/0022-4731(88)90295-6}} This may have clinical implications in the specific context of prostate cancer treatment. As an example, steroidal AR antagonists are able to increase prostate weight and accelerate prostate cancer cell growth in the absence of more potent AR agonists, and spironolactone has been found to accelerate progression of prostate cancer in case reports.{{cite journal | vauthors = Sundar S, Dickinson PD | title = Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate | journal = BMJ Case Rep | volume = 2012 | pages = bcr1120115238| year = 2012 | pmid = 22665559 | pmc = 3291010 | doi = 10.1136/bcr.11.2011.5238 }}{{cite journal | vauthors = Flynn T, Guancial EA, Kilari M, Kilari D | title = Case Report: Spironolactone Withdrawal Associated With a Dramatic Response in a Patient With Metastatic Castrate-Resistant Prostate Cancer | journal = Clin Genitourin Cancer | volume = 15| issue = 1| pages = e95–e97| year = 2016 | pmid = 27641657 | doi = 10.1016/j.clgc.2016.08.006 | s2cid = 38441469 }} In addition, whereas cyproterone acetate produces ambiguous genitalia via feminization in male fetuses when administered to pregnant animals,{{cite book | vauthors = James VH, Pasqualini JR | title = Hormonal Steroids: Proceedings of the Sixth International Congress on Hormonal Steroids | url = https://books.google.com/books?id=1VMJAwAAQBAJ&pg=PA391 | date = 22 October 2013 | publisher = Elsevier Science | isbn = 978-1-4831-9067-9 | pages = 391–}} it has been found to produce masculinization of the genitalia of female fetuses of pregnant animals. In contrast to steroidal AR antagonists, nonsteroidal AR antagonists are silent antagonists of the AR and do not activate the receptor.{{cite journal |vauthors=Caubet JF, Tosteson TD, Dong EW, Naylon EM, Whiting GW, Ernstoff MS, Ross SD |title=Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens |journal=Urology |volume=49 |issue=1 |pages=71–8 |year=1997 |pmid=9000189 |doi=10.1016/S0090-4295(96)00325-1 |quote=Because steroidal antiandrogens such as cyproterone acetate have intrinsic androgenic activity and lower antiandrogenic activity than the NSAAs such as flutamide and nilutamide,39–43 it is not surprising that the two classes of antiandrogens may have different efficacies.}}{{cite journal |vauthors=Singh SM, Gauthier S, Labrie F |title=Androgen receptor antagonists (antiandrogens): structure-activity relationships |journal=Current Medicinal Chemistry |volume=7 |issue=2 |pages=211–47 |date=February 2000 |pmid=10637363 |doi=10.2174/0929867003375371}} This may be why they have greater efficacy than steroidal AR antagonists in the treatment of prostate cancer and is an important reason as to why they have largely replaced them for this indication in medicine.

Nonsteroidal antiandrogens have relatively low affinity for the AR compared to steroidal AR ligands.{{cite journal | vauthors = Ayub M, Levell MJ | title = The effect of ketoconazole related imidazole drugs and antiandrogens on [3H] R 1881 binding to the prostatic androgen receptor and [3H]5 alpha-dihydrotestosterone and [3H]cortisol binding to plasma proteins | journal = J. Steroid Biochem. | volume = 33 | issue = 2 | pages = 251–5 | date = August 1989 | pmid = 2788775 | doi = 10.1016/0022-4731(89)90301-4 }} For example, bicalutamide has around 2% of the affinity of DHT for the AR and around 20% of the affinity of CPA for the AR. Despite their low affinity for the AR however, the lack of weak partial agonist activity of NSAAs appears to improve their potency relative to steroidal antiandrogens.{{cite journal | vauthors = Yamasaki K, Sawaki M, Noda S, Muroi T, Takakura S, Mitoma H, Sakamoto S, Nakai M, Yakabe Y | title = Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals | journal = Toxicology | volume = 195 | issue = 2–3 |pages=177–86 |year = 2004 | pmid = 14751673 | doi = 10.1016/j.tox.2003.09.012| bibcode = 2004Toxgy.195..177Y }} For example, although flutamide has about 10-fold lower affinity for the AR than CPA, it shows equal or slightly greater potency to CPA as an antiandrogen in bioassays. In addition, circulating therapeutic concentrations of nonsteroidal antiandrogens are very high, on the order of thousands of times higher than those of testosterone and DHT, and this allows them to efficaciously compete and block AR signaling.{{cite book| vauthors = Pratt WB |title= The Anticancer Drugs|url=https://books.google.com/books?id=nPR1L4K5HuEC&pg=PA220 |year=1994 |publisher=Oxford University Press |isbn=978-0-19-506739-2 |pages=220– |quote=In patients receiving flutamide at the usual dosage of 250 mg every 8 hours, the minimal plasma concentration of hydroxyflutamide is about 5 uM, which is 5,000 times the plasma concentration of testosterone (1 nM) in patients treated with an LHRH agonist.127 As hydroxyflutamide is only one percent as potent as testosterone in competing for binding to the androgen receptor,126 a plasma level of 5 uM hydroxyflutamide is required to ensure effective competition.127 [...] Both cyproterone acetate and flutamide have been demonstrated to be effective therapy (roughly equivalent to an estrogen) when used alone in the treatment of carcinoma of the prostate.123}}

AR antagonists may not bind to or block membrane androgen receptors (mARs), which are distinct from the classical nuclear AR.{{cite journal | vauthors = Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC | title = Molecular cell biology of androgen receptor signalling | journal = Int. J. Biochem. Cell Biol. | volume = 42 | issue = 6 | pages = 813–27 | year = 2010 | pmid = 19931639 | doi = 10.1016/j.biocel.2009.11.013 }}{{cite journal | vauthors = Wang C, Liu Y, Cao JM | title = G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids | journal = Int J Mol Sci | volume = 15 | issue = 9 | pages = 15412–25 | year = 2014 | pmid = 25257522 | pmc = 4200746 | doi = 10.3390/ijms150915412 | doi-access = free }}{{cite journal | vauthors = Lang F, Alevizopoulos K, Stournaras C | title = Targeting membrane androgen receptors in tumors | journal = Expert Opin. Ther. Targets | volume = 17 | issue = 8 | pages = 951–63 | year = 2013 | pmid = 23746222 | doi = 10.1517/14728222.2013.806491 | s2cid = 23918273 }} However, the mARs do not appear to be involved in masculinization. This is evidenced by the perfectly female phenotype of women with complete androgen insensitivity syndrome.{{cite book| vauthors = Pescovitz OH, Eugster EA |title=Pediatric Endocrinology: Mechanisms, Manifestations, and Management|url=https://books.google.com/books?id=9gvBlktAT6YC&pg=PA248|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-4059-3|pages=248–}}{{cite book| vauthors = Buonocore G, Bracci R, Weindling M |title=Neonatology: A Practical Approach to Neonatal Diseases|url=https://books.google.com/books?id=n_L2XpJbhLoC&pg=PA1012|date=28 January 2012|publisher=Springer Science & Business Media|isbn=978-88-470-1405-3|pages=1012–}} These women have a 46,XY karyotype (i.e., are genetically "male") and high levels of androgens but possess a defective AR and for this reason never masculinize. They are described as highly feminine, both physically as well as mentally and behaviorally.{{cite book| vauthors = Jordan-Young RM |title=Brain Storm|url=https://books.google.com/books?id=2V9UuOWMXOMC&pg=PA82|date=7 January 2011|publisher=Harvard University Press|isbn=978-0-674-05879-8|pages=82–}}{{cite book| vauthors = Blakemore JE, Berenbaum SA, Liben LS |title=Gender Development |url=https://books.google.com/books?id=PQ3Ylt6KnA4C&pg=PT115 |date=13 May 2013|publisher=Psychology Press|isbn=978-1-135-07932-1|pages=115–}}{{cite book| vauthors = Maggi M |title= Hormonal Therapy for Male Sexual Dysfunction|url=https://books.google.com/books?id=o_A9DnMVi3cC&pg=PA6|date=30 January 2012|publisher=John Wiley & Sons|isbn=978-0-470-65760-7|pages=6–}}

N-Terminal domain AR antagonists are a new type of AR antagonist that, unlike all currently marketed AR antagonists, bind to the N-terminal domain (NTD) of the AR rather than the ligand-binding domain (LBD).{{cite journal | vauthors = Imamura Y, Sadar MD | title = Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic | journal = International Journal of Urology | volume = 23 | issue = 8 | pages = 654–665 | date = August 2016 | pmid = 27302572 | pmc = 6680212 | doi = 10.1111/iju.13137 }} Whereas conventional AR antagonists bind to the LBD of the AR and competitively displace androgens, thereby preventing them from activating the receptor, AR NTD antagonists bind covalently to the NTD of the AR and prevent protein–protein interactions subsequent to activation that are required for transcriptional activity. As such, they are non-competitive and irreversible antagonists of the AR.{{cite journal | vauthors = De Mol E, Fenwick RB, Phang CT, Buzón V, Szulc E, de la Fuente A, Escobedo A, García J, Bertoncini CW, Estébanez-Perpiñá E, McEwan IJ, Riera A, Salvatella X | display-authors = 6 | title = EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor | journal = ACS Chemical Biology | volume = 11 | issue = 9 | pages = 2499–2505 | date = September 2016 | pmid = 27356095 | pmc = 5027137 | doi = 10.1021/acschembio.6b00182 }} Examples of AR NTD antagonists include bisphenol A diglycidyl ether (BADGE) and its derivatives EPI-001, ralaniten (EPI-002), and ralaniten acetate (EPI-506).{{cite journal | vauthors = Martinez-Ariza G, Hulme C | title = Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer | journal = Pharmaceutical Patent Analyst | volume = 4 | issue = 5 | pages = 387–402 | year = 2015 | pmid = 26389532 | doi = 10.4155/ppa.15.20 }} AR NTD antagonists are under investigation for the potential treatment of prostate cancer, and it is thought that they may have greater efficacy as antiandrogens relative to conventional AR antagonists. In accordance with this notion, AR NTD antagonists are active against splice variants of the AR, which conventional AR antagonists are not, and AR NTD antagonists are immune to gain-of-function mutations in the AR LBD that convert AR antagonists into AR agonists and commonly occur in prostate cancer.

Selective androgen receptor degraders (SARDs) are another new type of antiandrogen that has recently been developed.{{cite journal | vauthors = Lai AC, Crews CM | title = Induced protein degradation: an emerging drug discovery paradigm | journal = Nature Reviews. Drug Discovery | volume = 16 | issue = 2 | pages = 101–114 | date = February 2017 | pmid = 27885283 | pmc = 5684876 | doi = 10.1038/nrd.2016.211 }} They work by enhancing the degradation of the AR, and are analogous to selective estrogen receptor degraders (SERDs) like fulvestrant (a drug used to treat estrogen receptor-positive breast cancer). Similarly to AR NTD antagonists, it is thought that SARDs may have greater efficacy than conventional AR antagonists, and for this reason, they are under investigation for the treatment of prostate cancer.{{cite journal | vauthors = Lai KP, Huang CK, Chang YJ, Chung CY, Yamashita S, Li L, Lee SO, Yeh S, Chang C | display-authors = 6 | title = New therapeutic approach to suppress castration-resistant prostate cancer using ASC-J9 via targeting androgen receptor in selective prostate cells | journal = The American Journal of Pathology | volume = 182 | issue = 2 | pages = 460–473 | date = February 2013 | pmid = 23219429 | pmc = 3562731 | doi = 10.1016/j.ajpath.2012.10.029 }} An example of a SARD is dimethylcurcumin (ASC-J9), which is under development as a topical medication for the potential treatment of acne.{{Cite web | url = http://adisinsight.springer.com/drugs/800028542 | title = ASCJ 9 | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2017-12-24 | archive-date = 2018-03-04 | archive-url = https://web.archive.org/web/20180304204526/http://adisinsight.springer.com/drugs/800028542 | url-status = live }} SARDs like dimethylcurcumin differ from conventional AR antagonists and AR NTD antagonists in that they may not necessarily bind directly to the AR.

{{Main|Androgen synthesis inhibitor}}

Androgen synthesis inhibitors are enzyme inhibitors that prevent the biosynthesis of androgens. This process occurs mainly in the gonads and adrenal glands, but also occurs in other tissues like the prostate gland, skin, and hair follicles. These drugs include aminoglutethimide, ketoconazole,{{cite journal |vauthors=Witjes FJ, Debruyne FM, Fernandez del Moral P, Geboers AD | title = Ketoconazole high dose in management of hormonally pretreated patients with progressive metastatic prostate cancer. Dutch South-Eastern Urological Cooperative Group | journal = Urology | volume = 33 | issue = 5 | pages = 411–5 |date=May 1989 | pmid = 2652864 | doi = 10.1016/0090-4295(89)90037-X }} and abiraterone acetate.{{cite book| vauthors = Held-Warmkessel J |title= Contemporary Issues in Prostate Cancer: A Nursing Perspective|url=https://books.google.com/books?id=dZe4ZSVDdBsC&pg=PA275|year=2006|publisher=Jones & Bartlett Learning|isbn=978-0-7637-3075-8|pages=275–}} Aminoglutethimide inhibits cholesterol side-chain cleavage enzyme, also known as P450scc or CYP11A1, which is responsible for the conversion of cholesterol into pregnenolone and by extension the production of all steroid hormones, including the androgens. Ketoconazole and abiraterone acetate are inhibitors of the enzyme CYP17A1, also known as 17α-hydroxylase/17,20-lyase, which is responsible for the conversion of pregnane steroids into androgens, as well as the conversion of mineralocorticoids into glucocorticoids. Because these drugs all prevent the formation of glucocorticoids in addition to androgens, they must be combined with a glucocorticoid like prednisone to avoid adrenal insufficiency. A newer drug currently under development for treatment of prostate cancer, seviteronel, is selective for inhibition of the 17,20-lyase functionality of CYP17A1, and for this reason, unlike earlier drugs, does not require concomitant treatment with a glucocorticoid.{{cite journal | vauthors = Bird IM, Abbott DH | title = The hunt for a selective 17,20 lyase inhibitor; learning lessons from nature | journal = J. Steroid Biochem. Mol. Biol. | volume = 163 | pages = 136–46 | year = 2016 | pmid = 27154414 | doi = 10.1016/j.jsbmb.2016.04.021 | pmc=5046225}}

5α-Reductase inhibitors such as finasteride and dutasteride are inhibitors of 5α-reductase, an enzyme that is responsible for the formation of DHT from testosterone.{{Cite journal |vauthors=Flores E, Bratoeff E, Cabeza M, Ramirez E, Quiroz A, Heuze I | title = Steroid 5alpha-reductase inhibitors | journal = Mini-Reviews in Medicinal Chemistry | volume = 3 | pages = 225–37 |date=May 2003 | pmid = 12570838 | issue = 3 | doi=10.2174/1389557033488196}} DHT is between 2.5- and 10-fold more potent than testosterone as an androgen{{cite book| vauthors = Mozayani A, Raymon L |title=Handbook of Drug Interactions: A Clinical and Forensic Guide|url=https://books.google.com/books?id=NhBJ6kg_uP0C&pg=PA656|date=18 September 2011|publisher=Springer Science & Business Media|isbn=978-1-61779-222-9|pages=656–}} and is produced in a tissue-selective manner based on expression of 5α-reductase.{{cite book| vauthors = Bhagavan NV |title=Medical Biochemistry|url=https://books.google.com/books?id=b7Dc9bOs9uAC&pg=PA787 |year=2002|publisher=Academic Press|isbn=978-0-12-095440-7|pages=787–}} Tissues in which DHT forms at a high rate include the prostate gland, skin, and hair follicles. In accordance, DHT is involved in the pathophysiology of benign prostatic hyperplasia, pattern hair loss, and hirsutism, and 5α-reductase inhibitors are used to treat these conditions.{{cite journal | vauthors = Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS | title = Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review | journal = J Clin Aesthet Dermatol | volume = 9 | issue = 7 | pages = 56–62 | year = 2016 | pmid = 27672412 | pmc = 5023004 }}

File:Estradiol and testosterone levels with a single intramuscular injection of 320 mg polyestradiol phosphate in men.png, a polymeric estradiol ester and prodrug, in men with prostate cancer.{{cite journal | vauthors = Stege R, Gunnarsson PO, Johansson CJ, Olsson P, Pousette A, Carlström K | title = Pharmacokinetics and testosterone suppression of a single dose of polyestradiol phosphate (Estradurin) in prostatic cancer patients | journal = Prostate | volume = 28 | issue = 5 | pages = 307–10 | year = 1996 | pmid = 8610057 | doi = 10.1002/(SICI)1097-0045(199605)28:5<307::AID-PROS6>3.0.CO;2-8 | s2cid = 33548251 }}]]

File:Testosterone and luteinizing hormone levels with 100 mg per day oral cyproterone acetate in men.png in men.{{cite journal| vauthors = Fourcade RO, McLeod D |title=Tolerability of Antiandrogens in the Treatment of Prostate Cancer|journal=UroOncology|volume=4|issue=1|year=2015|pages=5–13|issn=1561-0950|doi=10.1080/1561095042000191655}}]]

Antigonadotropins are drugs that suppress the GnRH-mediated secretion of gonadotropins from the pituitary gland. Gonadotropins include luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and are peptide hormones that signal the gonads to produce sex hormones. By suppressing gonadotropin secretion, antigonadotropins suppress gonadal sex hormone production and by extension circulating androgen levels. GnRH modulators, including both GnRH agonists and GnRH antagonists, are powerful antigonadotropins that are able to suppress androgen levels by 95% in men.{{cite book|author=Urotext|title=Urotext-Luts: Urology|url=https://books.google.com/books?id=6zjtA37qDsMC&pg=PA71|date=1 January 2001|publisher=Urotext|isbn=978-1-903737-03-3|pages=71–|access-date=2016-12-27|archive-date=2023-01-11|archive-url=https://web.archive.org/web/20230111061908/https://books.google.com/books?id=6zjtA37qDsMC&pg=PA71|url-status=live}} In addition, estrogens and progestogens are antigonadotropins via exertion of negative feedback on the hypothalamic–pituitary–gonadal axis (HPG axis).{{cite journal |vauthors=de Lignières B, Silberstein S | title = Pharmacodynamics of oestrogens and progestogens | journal = Cephalalgia: An International Journal of Headache | volume = 20 | issue = 3 | pages = 200–7 |date=April 2000 | pmid = 10997774 | doi = 10.1046/j.1468-2982.2000.00042.x| s2cid = 40392817 | doi-access = free }}{{cite journal | vauthors = Neumann F | title = The physiological action of progesterone and the pharmacological effects of progestogens--a short review | journal = Postgraduate Medical Journal | volume = 54 | issue = Suppl 2 | pages = 11–24 | year = 1978 | pmid = 368741 }} High-dose estrogens are able to suppress androgen levels to castrate levels in men similarly to GnRH modulators,{{cite journal | vauthors = Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R | title = Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial | journal = Br J Urol | volume = 52 | issue = 3 | pages = 208–15 | year = 1980 | pmid = 7000222 | doi = 10.1111/j.1464-410x.1980.tb02961.x}} while high-dose progestogens are able to suppress androgen levels by up to approximately 70 to 80% in men.{{cite book|vauthors=Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA|title=Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set|url=https://books.google.com/books?id=fu3BBwAAQBAJ&pg=PA2938|date=25 August 2011|publisher=Elsevier Health Sciences|isbn=978-1-4160-6911-9|pages=2938–|access-date=27 December 2016|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111061407/https://books.google.com/books?id=fu3BBwAAQBAJ&pg=PA2938|url-status=live}}{{cite journal | vauthors = Kjeld JM, Puah CM, Kaufman B, Loizou S, Vlotides J, Gwee HM, Kahn F, Sood R, Joplin GF | title = Effects of norgestrel and ethinyloestradiol ingestion on serum levels of sex hormones and gonadotrophins in men | journal = Clinical Endocrinology | volume = 11 | issue = 5 | pages = 497–504 | year = 1979 | pmid = 519881 | doi = 10.1111/j.1365-2265.1979.tb03102.x| s2cid = 5836155 }}

Examples of GnRH agonists include leuprorelin (leuprolide) and goserelin, while an example of a GnRH antagonist is cetrorelix. Estrogens that are or that have been used as antigonadotropins include estradiol, estradiol esters like estradiol valerate, estradiol undecylate, and polyestradiol phosphate, conjugated estrogens, ethinylestradiol, diethylstilbestrol (no longer widely used), and bifluranol.{{cite journal | vauthors = Norman G, Dean ME, Langley RE, Hodges ZC, Ritchie G, Parmar MK, Sydes MR, Abel P, Eastwood AJ | title = Parenteral oestrogen in the treatment of prostate cancer: a systematic review | journal = Br. J. Cancer | volume = 98 | issue = 4 | pages = 697–707 | year = 2008 | pmid = 18268497 | pmc = 2259178 | doi = 10.1038/sj.bjc.6604230 }}{{cite journal | vauthors = Dekanski JB | title = Anti-prostatic activity of bifluranol, a fluorinated bibenzyl | journal = Br. J. Pharmacol. | volume = 71 | issue = 1 | pages = 11–6 | year = 1980 | pmid = 6258683 | pmc = 2044395 | doi = 10.1111/j.1476-5381.1980.tb10903.x}} Progestogens that are used as antigonadotropins include chlormadinone acetate, cyproterone acetate, gestonorone caproate,{{cite journal | vauthors = Sander S, Nissen-Meyer R, Aakvaag A | title = On gestagen treatment of advanced prostatic carcinoma | journal = Scand. J. Urol. Nephrol. | volume = 12 | issue = 2 | pages = 119–21 | year = 1978 | pmid = 694436 | doi = 10.3109/00365597809179977}} hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, and oxendolone.{{cite book| vauthors = Prentky RA, Burgess AW |title= Forensic Management of Sexual Offenders|url=https://books.google.com/books?id=-50Of8_n_TAC&pg=PA219 |date=31 July 2000|publisher=Springer Science & Business Media|isbn=978-0-306-46278-8|pages=219–}}{{cite journal | vauthors = Sudo K, Yamazaki I, Masuoka M, Nakayama R | title = Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins | journal = Acta Endocrinol Suppl (Copenh) | volume = 229 | pages = 53–66 | year = 1979 | pmid = 294107 | doi = 10.1530/acta.0.092s053}}

In addition to their antigonadotropic effects, estrogens are also functional antiandrogens by decreasing free concentrations of androgens via increasing the hepatic production of sex hormone-binding globulin (SHBG) and by extension circulating SHBG levels.{{cite book| vauthors = Nieschlag E, Behre HM, Nieschlag S |title=Testosterone: Action, Deficiency, Substitution |url= https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA62 |date=26 July 2012|publisher=Cambridge University Press|isbn=978-1-107-01290-5|pages=62–}}{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=World Health Organization|author3=International Agency for Research on Cancer|title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA157|year=2007|publisher=World Health Organization|isbn=978-92-832-1291-1|pages=157–}}{{cite journal | vauthors = Coss CC, Jones A, Parke DN, Narayanan R, Barrett CM, Kearbey JD, Veverka KA, Miller DD, Morton RA, Steiner MS, Dalton JT | title = Preclinical characterization of a novel diphenyl benzamide selective ERα agonist for hormone therapy in prostate cancer | journal = Endocrinology | volume = 153 | issue = 3 | pages = 1070–81 | year = 2012 | pmid = 22294742 | doi = 10.1210/en.2011-1608 | doi-access = free }} Combined oral contraceptives containing ethinylestradiol have been found to increase circulating SHBG levels by 2- to 4-fold in women and to reduce free testosterone concentrations by 40 to 80%. However, combined oral contraceptives that contain the particularly androgenic progestin levonorgestrel have been found to increase SHBG levels by only 50 to 100%, which is likely because activation of the AR in the liver has the opposite effect of estrogen and suppresses production of SHBG.{{cite book| vauthors = Krishna UR, Sheriar NK |title=Adolescent Gynecology (pb)|url=https://books.google.com/books?id=B8hcC17D154C&pg=PA121|date=1 January 2000|publisher=Orient Blackswan|isbn=978-81-250-1793-6|pages=121–}} Levonorgestrel and certain other 19-nortestosterone progestins used in combined oral contraceptives like norethisterone also directly bind to and displace androgens from SHBG, which may additionally antagonize the functional antiandrogenic effects of ethinylestradiol.{{cite book| vauthors = Filshie M, Guillebaud J |title=Contraception: Science and Practice|url=https://books.google.com/books?id=Ug3-BAAAQBAJ&pg=PA26 |date=22 October 2013 |publisher=Elsevier Science |isbn=978-1-4831-6366-6 |pages=26–}} In men, a study found that treatment with a relatively low dosage of 20 μg/day ethinylestradiol for 5 weeks increased circulating SHBG levels by 150% and, due to the accompanying decrease free testosterone levels, increased total circulating levels of testosterone by 50% (via reduced negative feedback by androgens on the HPG axis).

Estrogens at high doses can partially suppress adrenal androgen production.{{cite book | vauthors = Oettel M | title=Estrogens and Antiestrogens II | series=Handbook of Experimental Pharmacology | chapter=Estrogens and Antiestrogens in the Male | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | year=1999 | volume=135 / 2 | issn=0171-2004 | doi=10.1007/978-3-642-60107-1_25 | pages=505–571| isbn=978-3-642-64261-6 }}{{cite book| vauthors = Margioris AN, Chrousos GP |title=Adrenal Disorders|url=https://books.google.com/books?id=XB73BwAAQBAJ&pg=PA84|date=20 April 2001|publisher=Springer Science & Business Media|isbn=978-1-59259-101-5|pages=84–}}{{cite journal | vauthors = Polderman KH, Gooren LJ, van der Veen EA | title = Effects of gonadal androgens and oestrogens on adrenal androgen levels | journal = Clin. Endocrinol. (Oxf) | volume = 43 | issue = 4 | pages = 415–21 | date = October 1995 | pmid = 7586614 | doi = 10.1111/j.1365-2265.1995.tb02611.x | s2cid = 6815423 }}{{cite journal | vauthors = Stege R, Eriksson A, Henriksson P, Carlström K | title = Orchidectomy or oestrogen treatment in prostatic cancer: effects on serum levels of adrenal androgens and related steroids | journal = Int. J. Androl. | volume = 10 | issue = 4 | pages = 581–7 | date = August 1987 | pmid = 2958420 | doi = 10.1111/j.1365-2605.1987.tb00357.x | doi-access = free }}{{cite journal | vauthors = Pousette A, Carlström K, Stege R | title = Androgens during different modes of endocrine treatment of prostatic cancer | journal = Urol. Res. | volume = 17 | issue = 2 | pages = 95–8 | date = 1989 | pmid = 2734983 | doi = 10.1007/BF00262027 | s2cid = 25309877 }}{{cite journal | vauthors = Cox RL, Crawford ED | title = Estrogens in the treatment of prostate cancer | journal = J. Urol. | volume = 154 | issue = 6 | pages = 1991–8 | date = December 1995 | pmid = 7500443 | doi = 10.1016/S0022-5347(01)66670-9 }} A study found that treatment with a high-dose ethinylestradiol (100 μg/day) reduced levels of major circulating adrenal androgens by 27 to 48% in transgender women. Decreased adrenal androgens with estrogens is apparent with oral and synthetic estrogens like ethinylestradiol and estramustine phosphate but is minimal with parenteral bioidentical estradiol forms like polyestradiol phosphate. It is thought to be mediated via a hepatic mechanism, probably increased corticosteroid-binding globulin (CBG) production and levels and compensatory changes in adrenal steroid production (e.g., shunting of adrenal androgen synthesis to cortisol production). It is notable in this regard that oral and synthetic estrogens, due to the oral first pass and resistance to hepatic metabolism, have much stronger influences on liver protein synthesis than parenteral estradiol.{{cite journal | vauthors = von Schoultz B, Carlström K, Collste L, Eriksson A, Henriksson P, Pousette A, Stege R | title = Estrogen therapy and liver function--metabolic effects of oral and parenteral administration | journal = Prostate | volume = 14 | issue = 4 | pages = 389–95 | date = 1989 | pmid = 2664738 | doi = 10.1002/pros.2990140410 | s2cid = 21510744 | url = }} The decrease in adrenal androgen levels with high-dose estrogen therapy may be beneficial in the treatment of prostate cancer.

Anticorticotropins such as glucocorticoids and mineralocorticoids work by exerting negative feedback on the hypothalamic–pituitary–adrenal axis (HPA axis), thereby inhibiting the secretion of corticotropin-releasing hormone (CRH) and hence adrenocorticotropic hormone (ACTH; corticotropin) and consequently suppressing the production of androgen prohormones like dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione in the adrenal gland.{{cite book| vauthors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM |title= Williams Textbook of Endocrinology E-Book|url=https://books.google.com/books?id=nbg1QOAObicC&pg=PA753|date=12 May 2011|publisher=Elsevier Health Sciences|isbn=978-1-4377-3600-7|pages=753–}}{{cite book | vauthors = Kumar V, Abbas AK, Fausto N, Aster JC |title=Robbins & Cotran Pathologic Basis of Disease E-Book|url=https://books.google.com/books?id=_1Zmvm4JVNcC&pg=PA1154|date=10 June 2009|publisher=Elsevier Health Sciences|isbn=978-1-4377-2015-0|pages=1154–}} They are rarely used clinically as functional antiandrogens, but are used as such in the case of congenital adrenal hyperplasia in girls and women, in which there are excessive production and levels of adrenal androgens due to glucocorticoid deficiency and hence HPA axis overactivity.

In women with insulin resistance, such as those with polycystic ovary syndrome, androgen levels are often elevated.{{cite journal | vauthors = Nikolakis G, Kyrgidis A, Zouboulis CC | title = Is There a Role for Antiandrogen Therapy for Hidradenitis Suppurativa? A Systematic Review of Published Data | journal = American Journal of Clinical Dermatology | volume = 20 | issue = 4 | pages = 503–513 | date = August 2019 | pmid = 31073704 | doi = 10.1007/s40257-019-00442-w | s2cid = 149443722 }} Metformin, an insulin-sensitizing medication, has indirect antiandrogenic effects in such women, decreasing testosterone levels by as much as 50% secondary to its beneficial effects on insulin sensitivity.{{cite journal | vauthors = Patel R, Shah G | title = Effect of metformin on clinical, metabolic and endocrine outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials | journal = Current Medical Research and Opinion | volume = 33 | issue = 9 | pages = 1545–1557 | date = September 2017 | pmid = 28058854 | doi = 10.1080/03007995.2017.1279597 | s2cid = 4391302 }}{{cite journal | vauthors = Guan Y, Wang D, Bu H, Zhao T, Wang H | title = The Effect of Metformin on Polycystic Ovary Syndrome in Overweight Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | journal = International Journal of Endocrinology | volume = 2020 | issue = | pages = 5150684 | date = 2020 | pmid = 33014044 | pmc = 7519180 | doi = 10.1155/2020/5150684 | doi-access = free }}

Ovandrotone albumin (Fecundin, Ovastim) and Androvax (androstenedione albumin) are immunogens and vaccines against androstenedione that are used in veterinary medicine to improve fecundity (reproductive rate) in ewes (adult female sheep).{{cite book| vauthors = Sreenan JM, Diskin MG |title=Embryonic Mortality in Farm Animals |url= https://books.google.com/books?id=QKFyBgAAQBAJ&pg=PA172 |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-5038-2|pages=172–}}{{cite book| vauthors = Jindal SK, Sharma MC |title=Biotechnology in Animal Health and Production |url= https://books.google.com/books?id=e9yFom2LWTcC&pg=PA77|year=2010|publisher=New India Publishing|isbn=978-93-80235-35-6|pages=77–}} The generation of antibodies against androstenedione by these agents is thought to decrease circulating levels of androstenedione and its metabolites (e.g., testosterone and estrogens), which in turn increases the activity of the HPG axis via reduced negative feedback and increases the rate of ovulation, resulting in greater fertility and fecundity.

{{See also|List of antiandrogens|List of steroidal antiandrogens}}

Antiandrogens can be divided into several different types based on chemical structure, including steroidal antiandrogens, nonsteroidal antiandrogens, and peptides. Steroidal antiandrogens include compounds like cyproterone acetate, spironolactone, estradiol, abiraterone acetate, and finasteride; nonsteroidal antiandrogens include compounds like bicalutamide, elagolix, diethylstilbestrol, aminoglutethimide, and ketoconazole; and peptides include GnRH analogues like leuprorelin and cetrorelix.{{citation needed|date=May 2021}}

{{See also|Discovery and development of antiandrogens}}

Antigonadotropins like estrogens and progestogens were both first introduced in the 1930s.{{cite book| vauthors = Fritz MA, Speroff L |title=Clinical Gynecologic Endocrinology and Infertility|url=https://books.google.com/books?id=KZLubBxJEwEC&pg=PA750|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-4847-3|pages=750–751, 963}} The beneficial effects of androgen deprivation via surgical castration or high-dose estrogen therapy on prostate cancer were discovered in 1941.{{rp|56}}{{cite book | vauthors = Kavoussi P, Costabile RA, Salonia A |title=Clinical Urologic Endocrinology: Principles for Men's Health |url=https://books.google.com/books?id=osURyQf4-2EC&pg=PR7 |date=17 October 2012 |publisher=Springer Science & Business Media |isbn=978-1-4471-4404-5 |pages=7–}} AR antagonists were first discovered in the early 1960s. The steroidal antiandrogen cyproterone acetate was discovered in 1961 and introduced in 1973, and is often described as the first antiandrogen to have been marketed.{{cite book|title=Advances in Drug Research|url=https://books.google.com/books?id=f1aKl17UpxkC&pg=PA34|date=12 August 1997|publisher=Academic Press|isbn=978-0-08-052628-7|pages=34–}} However, spironolactone was introduced in 1959,{{cite book|vauthors=Jugdutt BI|title=Aging and Heart Failure: Mechanisms and Management|url=https://books.google.com/books?id=0e23BAAAQBAJ&pg=PA175|date=19 February 2014|publisher=Springer Science & Business Media|isbn=978-1-4939-0268-2|pages=175–|access-date=27 December 2016|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111122900/https://books.google.com/books?id=0e23BAAAQBAJ&pg=PA175|url-status=live}}{{cite book| vauthors = Wermuth CG |title=The Practice of Murl=https://books.google.com/books?id=Qmt1_DQkCpEC&pg=PA34|date=2 May 2011|publisher=Academic Press|isbn=978-0-08-056877-5|pages=34–|author-link = Camille Georges Wermuth}} although its antiandrogen effects were not recognized or taken advantage of until later and were originally an unintended off-target action of the drug.{{cite book| vauthors = Azziz R |title=Androgen Excess Disorders in Women|url=https://books.google.com/books?id=Ch-BsGAOtucC&pg=PA382|date=8 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-179-6|pages=382–}} In addition to spironolactone, chlormadinone acetate and megestrol acetate are steroidal antiandrogens that are weaker than cyproterone acetate but were also introduced earlier, in the 1960s.{{cite book| vauthors = Runnebaum BC, Rabe T, Kiesel L |title=Female Contraception: Update and Trends|url=https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA136|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-73790-9|pages=136–}}{{cite book| vauthors = Orfanos CE, Montagna W, Stüttgen G |title=Hair Research: Status and Future Aspects; Proceedings of the First International Congress on Hair Research, Hamburg, March 13th–16, 1979|url=https://books.google.com/books?id=4gBJCAAAQBAJ&pg=PT587|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-81650-5|pages=587–}}{{cite book| vauthors = Marks L |title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=_i-s4biQs7MC&pg=PA76|year=2010|publisher=Yale University Press|isbn=978-0-300-16791-7|pages=76–78}} Other early steroidal antiandrogens that were developed around this time but were never marketed include benorterone (SKF-7690; 17α-methyl-B-nortestosterone), BOMT (Ro 7–2340), cyproterone (SH-80881), and trimethyltrienolone (R-2956).{{cite book| vauthors = Horsky J, Presl J |title=Ovarian Function and its Disorders: Diagnosis and Therapy|url=https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA112|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-8195-9|pages=112–}}{{cite book|title=Vitamins and Hormones|url=https://books.google.com/books?id=5ZbLRONHoDoC&pg=PA682|date=18 May 1976|publisher=Academic Press|isbn=978-0-08-086630-7|pages=682–}}

The nonsteroidal antiandrogen flutamide was first reported in 1967. It was introduced in 1983 and was the first nonsteroidal antiandrogen marketed.{{cite book| vauthors = Neal DE |title=Tumours in Urology|url=https://books.google.com/books?id=k28yBwAAQBAJ&pg=PT233|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4471-2086-5|pages=233–}}{{cite book| vauthors = Ottow E, Weinmann H |title= Nuclear Receptors as Drug Targets|url=https://books.google.com/books?id=iATfLbPgRugC&pg=PA255|date=8 September 2008|publisher=John Wiley & Sons|isbn=978-3-527-62330-3|pages=255–}} Another early nonsteroidal antiandrogen,{{cite book| vauthors = Singhal RL, Thomas JA |title=Cellular Mechanisms Modulating Gonadal Action|url=https://books.google.com/books?id=2eNqAAAAMAAJ|date=1 January 1976|publisher=University Park Press|isbn=978-0-8391-0776-7|page=239}} DIMP (Ro 7–8117), which is structurally related to thalidomide{{cite journal | vauthors = Liu B, Su L, Geng J, Liu J, Zhao G | title = Developments in nonsteroidal antiandrogens targeting the androgen receptor | journal = ChemMedChem | volume = 5 | issue = 10 | pages = 1651–1661 | date = October 2010 | pmid = 20853390 | doi = 10.1002/cmdc.201000259 | s2cid = 23228778 }} and is a relatively weak antiandrogen,{{cite journal | vauthors = Heyns W, Verhoeven G, De Moor P | title = Androgen binding in rat uterus cytosol. Study of the specificity | journal = Journal of Steroid Biochemistry | volume = 7 | issue = 5 | pages = 335–343 | date = May 1976 | pmid = 180344 | doi = 10.1016/0022-4731(76)90092-3 }}{{cite book|title=Annual Reports in Medicinal Chemistry|url=https://books.google.com/books?id=qsFCGskRHZQC&pg=PA182|date=16 September 1986|publisher=Academic Press|isbn=978-0-08-058365-5|pages=182–}} was first described in 1973 and was never marketed.{{cite journal | vauthors = Boris A, Scott JW, DeMartino L, Cox DC | title = Endocrine profile of a nonsteroidal antiandrogen N-(3,5-dimethyl-4-isoxazolylmethyl)phthalimide (DIMP) | journal = Acta Endocrinologica | volume = 72 | issue = 3 | pages = 604–614 | date = March 1973 | pmid = 4739363 | doi = 10.1530/acta.0.0720604 }} Flutamide was followed by nilutamide in 1989, and bicalutamide in 1995.{{cite book|vauthors=Bégué JP, Bonnet-Delpon D|title=Bioorganic and Medicinal Chemistry of Fluorine|url=https://books.google.com/books?id=QMVSvZ-R7I0C&pg=PA327|date=2 June 2008|publisher=John Wiley & Sons|isbn=978-0-470-28187-1|pages=327–|access-date=27 December 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112173104/https://books.google.com/books?id=QMVSvZ-R7I0C&pg=PA327|url-status=live}} In addition to these three drugs, which have been regarded as first-generation nonsteroidal antiandrogens, the second-generation nonsteroidal antiandrogens enzalutamide and apalutamide were introduced in 2012 and 2018, respectively.{{cite journal | vauthors = Menon MP, Higano CS | title = Enzalutamide, a second generation androgen receptor antagonist: development and clinical applications in prostate cancer | journal = Current Oncology Reports | volume = 15 | issue = 2 | pages = 69–75 | date = April 2013 | pmid = 23341368 | doi = 10.1007/s11912-013-0293-9 | s2cid = 8725297 }}{{cite journal | vauthors = Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL | display-authors = 6 | title = Development of a second-generation antiandrogen for treatment of advanced prostate cancer | journal = Science | volume = 324 | issue = 5928 | pages = 787–790 | date = May 2009 | pmid = 19359544 | pmc = 2981508 | doi = 10.1126/science.1168175 | bibcode = 2009Sci...324..787T }}{{Cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596768.htm|title=FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint|website=Food and Drug Administration|date=24 March 2020|access-date=1 April 2018|archive-date=23 April 2019|archive-url=https://web.archive.org/web/20190423072230/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596768.htm|url-status=dead}} They differ from the earlier nonsteroidal antiandrogens namely in that they are much more efficacious in comparison.

The androgen synthesis inhibitors aminoglutethimide and ketoconazole were first marketed in 1960 and 1977, respectively,{{cite book| vauthors = Sneader W |title=Drug Discovery: A History|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA367|date=23 June 2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2|pages=367–}}{{cite book|vauthors=Golan DE|title=Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy|url=https://books.google.com/books?id=az8uSDkB0mgC&pg=PA624|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-8355-2|pages=624–|access-date=2016-12-27|archive-date=2023-01-10|archive-url=https://web.archive.org/web/20230110131048/https://books.google.com/books?id=az8uSDkB0mgC&pg=PA624|url-status=live}} and the newer drug abiraterone acetate was introduced in 2011.{{cite book|title=Prostate Cancer|url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PA518|date=20 December 2011|publisher=Demos Medical Publishing|isbn=978-1-935281-91-7|pages=518–}} GnRH modulators were first introduced in the 1980s.{{cite book| vauthors = Bowsher W, Carter A |title= Challenges in Prostate Cancer|url=https://books.google.com/books?id=E3VNhLkqPmUC&pg=PA138|date=15 April 2008|publisher=John Wiley & Sons|isbn=978-1-4051-7177-9|pages=138–}} The 5α-reductase inhibitors finasteride and dutasteride were introduced in 1992. and 2002. respectively.{{cite book| vauthors = Allahbadia G, Agrawal R, Merchant R |title=Polycystic Ovary Syndrome|url=https://books.google.com/books?id=HX0JxcrWJvAC&pg=PA184|year=2007|publisher=Anshan|isbn=978-1-904798-74-3|pages=184–}}{{cite book|title=Frontiers in Medicinal Chemistry|url=https://books.google.com/books?id=b7hCWvdP5OYC&pg=PA329|year=2010|publisher=Bentham Science Publishers|isbn=978-1-60805-208-0|pages=329–}} Elagolix, the first orally active GnRH modulator to be marketed, was introduced in 2018.{{Cite web | url = https://adisinsight.springer.com/drugs/800020238 | title = Elagolix - Abbvie/Neurocrine Biosciences | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2018-07-30 | archive-date = 2018-09-20 | archive-url = https://web.archive.org/web/20180920082806/https://adisinsight.springer.com/drugs/800020238 | url-status = live }}

The following is a timeline of events in the history of antiandrogens:{{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 }}

• 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{{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 }}
• 1960: Spironolactone is first introduced for medical use, as an antimineralocorticoid
• 1961: The steroidal antiandrogen cyproterone acetate is first synthesized{{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 }}
• 1962: Spironolactone is first reported to produce gynecomastia in men{{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}}
• 1966: Benorterone is the first known antiandrogen to be studied clinically, to treat acne and hirsutism in women{{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 }}{{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 }}
• 1963: The antiandrogenic activity of cyproterone acetate is discovered{{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}}{{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 }}
• 1967: A known antiandrogen, benorterone, is first reported to induce gynecomastia in males
• 1967: The first-generation nonsteroidal antiandrogen flutamide is first synthesized
• 1967: Cyproterone acetate was first studied clinically, to treat sexual deviance in men{{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 }}
• 1969: Cyproterone acetate was first studied in the treatment of acne, hirsutism, seborrhea, and scalp hair loss in women{{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 }}
• 1969: The antiandrogenic activity of spironolactone is discovered{{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}}
• 1972: The antiandrogenic activity of flutamide is first reported{{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 }}{{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 }}
• 1973: Cyproterone acetate was first introduced for medical use, to treat sexual deviance{{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 }}
• 1977: The first-generation antiandrogen nilutamide is first described{{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}}
• 1978: Spironolactone is first studied in the treatment of hirsutism in women{{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}}
• 1979: Combined androgen blockade is first studied{{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 }}{{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 }}
• 1980: Medical castration via a GnRH analogue is first achieved{{Citation needed|date=March 2020}}
• 1982: The first-generation antiandrogen bicalutamide is first described{{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}}
• 1982: Combined androgen blockade for prostate cancer is developed
• 1983: Flutamide is first introduced, in Chile, for medical use, to treat prostate cancer{{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}}{{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}}
• 1987: Nilutamide is first introduced, in France, for medical use, to treat prostate cancer
• 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{{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–}}
• 1989: Flutamide is first studied in the treatment of hirsutism in women
• 1992: The androgen synthesis inhibitor abiraterone acetate is first described{{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}}
• 1995: Bicalutamide is first introduced for medical use, to treat prostate cancer
• 1996: Nilutamide is first introduced for medical use in the United States, to treat prostate cancer{{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 }}
• 2006: The second-generation nonsteroidal antiandrogen enzalutamide is first describedSawyers, 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]
• 2007: The second-generation nonsteroidal antiandrogen apalutamide is first described{{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}}
• 2011: Abiraterone acetate is first introduced for medical use, to treat prostate cancer{{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}}
• 2012: Enzalutamide is first introduced for medical use, to treat prostate cancer{{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 }}
• 2018: Apalutamide is first introduced for medical use, to treat prostate cancer{{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 }}
• 2018: Elagolix is the first orally active GnRH antagonist to be introduced for medical use
• 2019: Relugolix is the second orally active GnRH antagonist to be introduced for medical use{{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 }}
• 2019: Darolutamide is first introduced for medical use, to treat prostate cancer{{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}}

The term antiandrogen is generally used to refer specifically to AR antagonists, as described by Dorfman (1970):{{cite journal | vauthors = Neumann F | title = Pharmacology and potential use of cyproterone acetate | journal = Hormone and Metabolic Research | volume = 9 | issue = 1 | pages = 1–13 | date = January 1977 | pmid = 66176 | doi = 10.1055/s-0028-1093574 | s2cid = 7224893 }}{{cite journal| vauthors = Dorfman RI |title=Biological Activity of Antiandrogens|journal=British Journal of Dermatology|volume=82|issue=s6|year=1970|pages=3|issn=0007-0963|doi=10.1111/j.1365-2133.1970.tb07998.x|s2cid=71393789}}

{{Blockquote|Antiandrogens are substances which prevent androgens from expressing their activity at target sites. The inhibitory effect of these substances, therefore, should be differentiated from compounds which decrease the synthesis and/or release of hypothalamic (releasing) factors, from anterior pituitary hormones (gonadotropins, particularly luteinizing hormone) and from material which acts directly on the gonads to inhibit biosynthesis and/or secretion of androgens.}}

However, in spite of the above, the term may also be used to describe functional antiandrogens like androgen synthesis inhibitors and antigonadotropins, including even estrogens and progestogens.{{cite book| vauthors = Gräf KJ, Brotherton J, Neumann F |title=Androgens II and Antiandrogens / Androgene II und Antiandrogene|chapter=Clinical Uses of Antiandrogens |year=1974 |pages=485–542|publisher=Springer |doi=10.1007/978-3-642-80859-3_7|isbn=978-3-642-80861-6}} For example, the progestogen and hence antigonadotropin medroxyprogesterone acetate is sometimes described as a steroidal antiandrogen, even though it is not an antagonist of the AR.{{cite book| vauthors = Vogelzang N |title=Comprehensive Textbook of Genitourinary Oncology|url=https://books.google.com/books?id=WIsiGZnZ_mgC&pg=PA316 |year=2006 |publisher= Lippincott Williams & Wilkins|isbn=978-0-7817-4984-8|pages=316–}}

{{See also|List of investigational sex-hormonal agents#Androgenics}}

There has been much interest and effort in the development of topical AR antagonists to treat androgen-dependent conditions like acne and pattern hair loss in males.{{cite book| vauthors = Helms RA, Quan DJ |title=Textbook of Therapeutics: Drug and Disease Management|url=https://books.google.com/books?id=aVmRWrknaWgC&pg=PA211|year=2006|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-5734-8|pages=211–}} Unfortunately, whereas systemic administration of antiandrogens is very effective in treating these conditions, topical administration has disappointingly been found generally to possess limited and only modest effectiveness, even when high-affinity steroidal AR antagonists like cyproterone acetate and spironolactone have been employed. Moreover, in the specific case of acne treatment, topical AR antagonists have been found much less effective compared to established treatments like benzoyl peroxide and antibiotics.

A variety of AR antagonists have been developed for topical use but have not completed development and hence have never been marketed. These include the steroidal AR antagonists cyproterone, rosterolone, and topterone and the nonsteroidal AR antagonists cioteronel, inocoterone acetate, RU-22930, RU-58642, and RU-58841. However, one topical AR antagonist, topilutamide (fluridil), has been introduced in a few European countries for the treatment of pattern hair loss in men. In addition, a topical 5α-reductase inhibitor and weak estrogen, alfatradiol, has also been introduced in some European countries for the same indication, although its effectiveness is controversial. Spironolactone has been marketed in Italy in the form of a topical cream under the brand name Spiroderm for the treatment of acne and hirsutism, but this formulation was discontinued and hence is no longer available.{{cite book|vauthors=Farid NR, Diamanti-Kandarakis E|title=Diagnosis and Management of Polycystic Ovary Syndrome|url=https://books.google.com/books?id=fgMYVxmPDnMC&pg=PA235|date=27 February 2009|publisher=Springer Science & Business Media|isbn=978-0-387-09718-3|pages=235–|access-date=30 December 2016|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111121904/https://books.google.com/books?id=fgMYVxmPDnMC&pg=PA235|url-status=live}}

Topical clascoterone, brand name Winlevi, was approved to treat acne in males and females in the United States in 2020.{{cite web | title=Clascoterone - Cosmo Pharmaceuticals | website=AdisInsight | date=12 February 2025 | url=https://adisinsight.springer.com/drugs/800026561 | access-date=8 May 2025}}{{cite journal | vauthors = Dhillon S | title = Clascoterone: First Approval | journal = Drugs | volume = 80 | issue = 16 | pages = 1745–1750 | date = November 2020 | pmid = 33030710 | doi = 10.1007/s40265-020-01417-6 | url = }} However, although significantly more effective than placebo, topical clascoterone, like previous topical antiandrogens that have been developed, showed modest effectiveness in treating acne in clinical trials, and it appeared to be far less effective than systemic spironolactone.{{cite journal | vauthors = Basendwh MA, Alharbi AA, Bukhamsin SA, Abdulwahab RA, Alaboud SA | title = The efficacy of Topical Clascoterone versus systematic spironolactone for treatment of acne vulgaris: A systematic review and network meta-analysis | journal = PLOS ONE | volume = 19 | issue = 5 | pages = e0298155 | date = 2024 | pmid = 38814916 | pmc = 11139337 | doi = 10.1371/journal.pone.0298155 | doi-access = free | bibcode = 2024PLoSO..1998155B | url = }}

Antiandrogens, such as cyproterone acetate, have been studied for potential use as male hormonal contraceptives.{{cite journal | vauthors = Neumann F, Diallo FA, Hasan SH, Schenck B, Traore I | title = The influence of pharmaceutical compounds on male fertility | journal = Andrologia | volume = 8 | issue = 3 | pages = 203–35 | date = 1976 | pmid = 793446 | doi = 10.1111/j.1439-0272.1976.tb02137.x| s2cid = 24859886 | doi-access = free }}{{cite journal | vauthors = Prasad MR, Rajalakshmi M | title = Target sites for suppressing fertility in the male | journal = Adv Sex Horm Res | volume = 2 | pages = 263–87 | date = 1976 | pmid = 797248 }}{{cite journal | vauthors = Ewing LL, Robaire B | title = Endogenous antispermatogenic agents: prospects for male contraception | journal = Annu. Rev. Pharmacol. Toxicol. | volume = 18 | pages = 167–87 | date = 1978 | pmid = 206192 | doi = 10.1146/annurev.pa.18.040178.001123 }}{{cite journal | vauthors = Gombe S | title = A review of the current status in male contraceptive studies | journal = East Afr Med J | volume = 60 | issue = 4 | pages = 203–11 | date = April 1983 | pmid = 6354690 }}{{cite book | vauthors = Srivastava RP, Bhaduri AP | title = Progress in Drug Research | chapter = Emerging concepts towards the development of contraceptive agents | series = Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progres des Recherches Pharmaceutiques | volume = 33 | pages = 267–315 | date = 1989 | pmid = 2687939 | doi = 10.1007/978-3-0348-9146-2_9| isbn = 978-3-0348-9925-3 |editor=Ernst Jucker |publisher=Birkhäuser }}{{cite journal | vauthors = Wu FC | title = Male contraception: current status and future prospects | journal = Clin. Endocrinol. (Oxf) | volume = 29 | issue = 4 | pages = 443–65 | date = October 1988 | pmid = 3075164 | doi = 10.1111/j.1365-2265.1988.tb02894.x| s2cid = 36608203 }}{{cite journal | vauthors = Nieschlag E, Zitzmann M, Kamischke A | title = Use of progestins in male contraception | journal = Steroids | volume = 68 | issue = 10–13 | pages = 965–72 | date = November 2003 | pmid = 14667989 | doi = 10.1016/s0039-128x(03)00135-1| s2cid = 22458746 }} While effective in suppressing male fertility, their use as monotherapies is precluded by side effects, such as androgen deficiency (e.g., demasculinization, sexual dysfunction, hot flashes, osteoporosis) and feminization (e.g., gynecomastia).{{cite journal | vauthors = Nieschlag E | title = Clinical trials in male hormonal contraception | journal = Contraception | volume = 82 | issue = 5 | pages = 457–70 | year = 2010 | pmid = 20933120 | doi = 10.1016/j.contraception.2010.03.020 | url = http://www.kup.at/kup/pdf/10172.pdf | access-date = 2019-07-08 | archive-date = 2020-12-05 | archive-url = https://web.archive.org/web/20201205082822/https://www.kup.at/kup/pdf/10172.pdf | url-status = live }} The combination of a primary antigonadotropin such as cyproterone acetate to prevent fertility and an androgen like testosterone to prevent systemic androgen deficiency, resulting in a selective antiandrogenic action locally in the testes, has been extensively studied and has shown promising results, but has not been approved for clinical use at this time.{{cite journal | vauthors = Rajalakshmi M | title = Male contraception: expanding reproductive choice | journal = Indian J. Exp. Biol. | volume = 43 | issue = 11 | pages = 1032–41 | date = November 2005 | pmid = 16313066 }}{{cite journal | vauthors = Chao JH, Page ST | title = The current state of male hormonal contraception | journal = Pharmacol. Ther. | volume = 163 | pages = 109–17 | date = July 2016 | pmid = 27016468 | doi = 10.1016/j.pharmthera.2016.03.012 }} Dimethandrolone undecanoate (developmental code name CDB-4521), an orally active dual AAS and progestogen, is under investigation as a potential male contraceptive and as the first male birth control pill.{{cite journal | vauthors = Attardi BJ, Hild SA, Reel JR | title = Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity | journal = Endocrinology | volume = 147 | issue = 6 | pages = 3016–26 | date = June 2006 | pmid = 16497801 | doi = 10.1210/en.2005-1524 | doi-access = free }}{{cite journal | vauthors = Ayoub R, Page ST, Swerdloff RS, Liu PY, Amory JK, Leung A, Hull L, Blithe D, Christy A, Chao JH, Bremner WJ, Wang C | title = Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive | journal = Andrology | volume = 5 | issue = 2 | pages = 278–285 | date = March 2017 | pmid = 27907978 | pmc = 5352517 | doi = 10.1111/andr.12303 }}

Antiandrogens such as bicalutamide, enzalutamide, and abiraterone acetate are under investigation for the potential treatment of breast cancer, including AR-expressing triple-negative breast cancer and other types of AR-expressing breast cancer.{{cite journal | vauthors = Fioretti FM, Sita-Lumsden A, Bevan CL, Brooke GN | title = Revising the role of the androgen receptor in breast cancer | journal = J. Mol. Endocrinol. | volume = 52 | issue = 3 | pages = R257–65 | date = June 2014 | pmid = 24740738 | doi = 10.1530/JME-14-0030 | doi-access = free }}{{cite journal | vauthors = Gucalp A, Traina TA | title = Targeting the androgen receptor in triple-negative breast cancer | journal = Curr Probl Cancer | volume = 40 | issue = 2–4 | pages = 141–150 | date = 2016 | pmid = 27816190 | pmc = 5580391 | doi = 10.1016/j.currproblcancer.2016.09.004 }}{{cite journal | vauthors = Arce-Salinas C, Riesco-Martinez MC, Hanna W, Bedard P, Warner E | title = Complete Response of Metastatic Androgen Receptor-Positive Breast Cancer to Bicalutamide: Case Report and Review of the Literature | journal = J. Clin. Oncol. | volume = 34 | issue = 4 | pages = e21–4 | date = February 2016 | pmid = 24888812 | doi = 10.1200/JCO.2013.49.8899 }}{{cite journal | vauthors = Héquet D, Mzoughi S, Rouzier R, Guccione E | title = [Androgen receptors in breast cancer: Expression, value and therapeutic prospects] | language = fr | journal = Bull Cancer | volume = 104 | issue = 4 | pages = 363–369 | date = April 2017 | pmid = 28216075 | doi = 10.1016/j.bulcan.2017.01.005 }}{{cite journal | vauthors = Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S, Coinu A, Martorana F, De Santo I, Del Mastro L, De Laurentiis M, Puglisi F, Arpino G | title = Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype | journal = Cancer Treat. Rev. | volume = 68 | pages = 102–110 | date = June 2018 | pmid = 29940524 | doi = 10.1016/j.ctrv.2018.06.005 | doi-access = free | hdl = 11567/914067 | hdl-access = free }}

Antiandrogens might be effective and useful in the treatment of obsessive–compulsive disorder (OCD).{{cite journal |vauthors=Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A |title=Anti-androgen drugs in the treatment of obsessive-compulsive disorder: a systematic review |journal=Curr Med Chem |date=December 2019 |volume=27 |issue=40 |pages=6825–6836 |pmid=31814547 |doi=10.2174/0929867326666191209142209|s2cid=208956450 }}

• Androgen insensitivity syndrome
• Antiandrogens in the environment
• Androgen replacement therapy

{{Reflist}}

{{refbegin}}

• {{cite book| vauthors = Neumann F, Steinbeck H |title=Androgens II and Antiandrogens / Androgene II und Antiandrogene|chapter=Antiandrogens|year=1974|pages=235–484|publisher=Springer |doi=10.1007/978-3-642-80859-3_6|isbn=978-3-642-80861-6}}
• {{cite book| vauthors = Gräf KJ, Brotherton J, Neumann F |title=Androgens II and Antiandrogens / Androgene II und Antiandrogene|chapter=Clinical Uses of Antiandrogens|year=1974|pages=485–542|publisher=Springer |doi=10.1007/978-3-642-80859-3_7|isbn=978-3-642-80861-6}}

{{refend}}

{{Androgens and antiandrogens}}

{{Androgen receptor modulators}}

{{Authority control}}

Category:Anaphrodisia

Category:Anti-acne preparations

Category:Hair loss medications

Category:Hair removal

Category:Hormonal antineoplastic drugs

Category:Prostate cancer

Category:Sex hormones

Category:Psychoactive drugs