Editing Antiandrogen (section)

==Side effects==
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.<ref name="pmid11121992">{{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 }}</ref><ref name="Thomas1997">{{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}}</ref> 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.<ref name="pmid11121992" /><ref name="pmid12603397">{{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 }}</ref><ref name="Priestman2012">{{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–}}</ref> These differences are thought related to the fact that antigonadotropins suppress androgen levels and by extension levels of [[Biological activity|bioactive]] [[metabolite]]s of androgens like [[estrogen]]s and [[neurosteroid]]s 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).<ref name="pmid11121992" /> As another example, the steroidal antiandrogens cyproterone acetate and spironolactone possess off-target actions including [[progestogen]]ic, [[antimineralocorticoid]], and/or [[glucocorticoid]] activity in addition to their antiandrogen activity, and these off-target activities can result in additional side effects.<ref name="Thomas1997" />

In males, the major [[side effect]]s of antiandrogens are [[demasculinization]] and [[feminization (biology)|feminization]].<ref name="pmid12667885">{{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}}</ref> These side effects include [[mastodynia|breast pain/tenderness]] and [[gynecomastia]] ([[breast development]]/[[breast enlargement|enlargement]]), reduced [[body hair]] growth/density, decreased [[muscle mass]] and [[muscle strength|strength]], [[gynoid fat distribution|feminine]] changes in [[body fat percentage|fat mass]] and [[fat distribution|distribution]], and reduced [[human penis size|penile length]] and [[testicle|testicular]] size.<ref name="pmid12667885" /> The rates of gynecomastia in men with selective AR antagonist monotherapy have been found to range from 30 to 85%.<ref name="pmid16321765">{{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 }}</ref> In addition, antiandrogens can cause [[infertility]], [[osteoporosis]], [[hot flash]]es, [[sexual dysfunction]] (including loss of [[libido]] and [[erectile dysfunction]]), [[depression (mood)|depression]], [[fatigue (medical)|fatigue]], [[anemia]], and decreased [[Ejaculation#Volume|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}}<ref name="pmid12667885" /> Conversely, the side effects of selective AR antagonists in women are minimal.<ref name="pmid24455796" /><ref name="Shapiro2012">{{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–}}</ref> However, antigonadotropic antiandrogens like cyproterone acetate can produce [[hypoestrogenism]], [[amenorrhea]], and osteoporosis in premenopausal women, among other side effects.<ref name="Becker2001" /><ref name="Futterweit2012">{{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–}}</ref><ref name="pmid20082945">{{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 }}</ref> In addition, androgen receptor antagonists can produce unfavorable effects on [[cholesterol]] levels, which long-term may increase the risk of [[cardiovascular disease]].<ref name="pmid28944709">{{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 = }}</ref><ref name="pmid19843067">{{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 = }}</ref><ref name="pmid33334002">{{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 }}</ref><ref name="pmid29211888">{{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. 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A number of antiandrogens have been associated with [[hepatotoxicity]].<ref name="pmid15604569">{{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 }}</ref> These include, to varying extents, cyproterone acetate, flutamide, nilutamide, bicalutamide, aminoglutethimide, and ketoconazole.<ref name="pmid15604569" /> In contrast, spironolactone, enzalutamide,<ref name="pmid25711765">{{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 }}</ref> 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 [[seizure]]s.{{citation needed|date=May 2021}}

In women who are [[pregnancy|pregnant]], antiandrogens can interfere with the androgen-mediated [[sexual differentiation]] of the [[genitalia]] and [[brain]] of male [[fetus]]es.<ref name="LeppertPeipert2004">{{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–}}</ref> 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]].<ref name="LeppertPeipert2004" /><ref name="RathusNevid2005">{{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}}</ref> As such, antiandrogens are [[teratogen]]s, and women who are pregnant should not be treated with an antiandrogen.<ref name="CamachoGharib2012" /> Moreover, women who can or may become pregnant are strongly recommended to take an antiandrogen only in combination with proper [[contraceptive|contraception]].<ref name="CamachoGharib2012" />