Editing Antiandrogen (section)

===Miscellaneous===

====Sex hormone-binding globulin modulators====
In addition to their antigonadotropic effects, estrogens are also functional antiandrogens by decreasing free concentrations of androgens via increasing the [[liver|hepatic]] production of [[sex hormone-binding globulin]] (SHBG) and by extension circulating SHBG levels.<ref name="NieschlagBehre2012">{{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–}}</ref><ref name="HumansOrganization2007">{{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–}}</ref><ref name="pmid22294742">{{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 }}</ref> [[Combined oral contraceptive]]s 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%.<ref name="HumansOrganization2007" /> However, combined oral contraceptives that contain the particularly androgenic progestin [[levonorgestrel]] have been found to increase SHBG levels by only 50 to 100%,<ref name="HumansOrganization2007" /> which is likely because activation of the AR in the liver has the opposite effect of estrogen and suppresses production of SHBG.<ref name="KrishnaR.2000">{{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–}}</ref> 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.<ref name="KrishnaR.2000"/><ref name="FilshieGuillebaud2013">{{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–}}</ref> In men, a study found that treatment with a relatively low dosage of 20&nbsp;μg/day ethinylestradiol for 5&nbsp;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).<ref name="NieschlagBehre2012" />

====Corticosteroid-binding globulin modulators====
[[Estrogen (medication)|Estrogens]] at high doses can partially suppress adrenal androgen production.<ref name="Oettel1999">{{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 }}</ref><ref name="MargiorisChrousos2001">{{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–}}</ref><ref name="pmid7586614">{{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 }}</ref><ref name="pmid2958420">{{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 }}</ref><ref name="pmid2734983">{{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 }}</ref><ref name="pmid7500443">{{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 }}</ref> A study found that treatment with a high-dose [[ethinylestradiol]] (100&nbsp;μg/day) reduced levels of major circulating [[adrenal androgen]]s by 27 to 48% in [[transgender women]].<ref name="Oettel1999" /><ref name="MargiorisChrousos2001" /><ref name="pmid7586614" /> Decreased adrenal androgens with estrogens is apparent with [[oral administration|oral]] and [[synthetic compound|synthetic]] estrogens like [[ethinylestradiol]] and [[estramustine phosphate]] but is minimal with [[parenteral administration|parenteral]] [[bioidentical]] [[estradiol (medication)|estradiol]] forms like [[polyestradiol phosphate]].<ref name="pmid2734983" /> It is thought to be mediated via a [[liver|hepatic]] mechanism, probably increased [[corticosteroid-binding globulin]] (CBG) [[biosynthesis|production]] and levels and compensatory changes in adrenal steroid production (e.g., shunting of adrenal androgen synthesis to [[cortisol]] production).<ref name="pmid2734983" /><ref name="pmid7500443" /> It is notable in this regard that oral and synthetic estrogens, due to the oral [[first pass effect|first pass]] and resistance to hepatic [[metabolism]], have much stronger influences on [[liver protein synthesis]] than parenteral estradiol.<ref name="pmid2664738">{{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 = }}</ref> The decrease in adrenal androgen levels with high-dose estrogen therapy may be beneficial in the treatment of [[prostate cancer]].<ref name="pmid7586614" /><ref name="pmid7500443" />

====Anticorticotropins====
[[Anticorticotropin]]s such as [[glucocorticoid]]s and [[mineralocorticoid]]s 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 prohormone]]s like [[dehydroepiandrosterone]] (DHEA), [[dehydroepiandrosterone sulfate]] (DHEA-S), and [[androstenedione]] in the [[adrenal gland]].<ref name="MelmedPolonsky2011">{{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–}}</ref><ref name="KumarAbbas2009">{{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–}}</ref> 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.<ref name="MelmedPolonsky2011" /><ref name="KumarAbbas2009" />

====Insulin sensitizers====
In women with [[insulin resistance]], such as those with [[polycystic ovary syndrome]], androgen levels are often elevated.<ref name="NikolakisKyrgidis2019">{{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 }}</ref> [[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.<ref name="NikolakisKyrgidis2019" /><ref name="pmid28058854">{{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 }}</ref><ref name="pmid33014044">{{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 }}</ref>

====Immunogens and vaccines====
[[Ovandrotone albumin]] (Fecundin, Ovastim) and [[Androvax]] (androstenedione albumin) are [[immunogen]]s and [[vaccine]]s against [[4-androstenedione|androstenedione]] that are used in [[veterinary medicine]] to improve [[fecundity]] (reproductive rate) in ewes (adult female sheep).<ref name="SreenanDiskin2012">{{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–}}</ref><ref name="JindalSharma2010">{{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–}}</ref> 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.<ref name="SreenanDiskin2012" /><ref name="JindalSharma2010" />