Editing Progestogen (medication) (section)

====Androgenic activity====
{{See also|Progestin-induced virilization}}

Some progestins have [[androgen]]ic activity and can produce androgenic [[side effect]]s such as increased [[sebum]] production ([[oily skin|oilier skin]]), [[acne]], and [[hirsutism]] (excessive facial/body hair growth), as well as changes in [[liver protein production]].<ref name="BullockBardin1977">{{cite journal | vauthors = Bullock LP, Bardin CW | title = Androgenic, synandrogenic, and antiandrogenic actions of progestins | journal = Annals of the New York Academy of Sciences | volume = 286 | issue = 1 Biochemical A | pages = 321–330 | date = March 1977 | pmid = 281183 | doi = 10.1111/j.1749-6632.1977.tb29427.x | s2cid = 33611807 | bibcode = 1977NYASA.286..321B }}</ref><ref name="Darney1995">{{cite journal | vauthors = Darney PD | title = The androgenicity of progestins | journal = The American Journal of Medicine | volume = 98 | issue = 1A | pages = 104S–110S | date = January 1995 | pmid = 7825629 | doi = 10.1016/S0002-9343(99)80067-9 }}</ref><ref name="CampagnoliClavel-Chapelon2005">{{cite journal | vauthors = Campagnoli C, Clavel-Chapelon F, Kaaks R, Peris C, Berrino F | title = Progestins and progesterone in hormone replacement therapy and the risk of breast cancer | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 96 | issue = 2 | pages = 95–108 | date = July 2005 | pmid = 15908197 | pmc = 1974841 | doi = 10.1016/j.jsbmb.2005.02.014 }}</ref> Only certain progestins are androgenic however, these being the [[testosterone]] derivatives and, to a lesser extent, the [[17α-hydroxyprogesterone]] derivatives [[medroxyprogesterone acetate]] and [[megestrol acetate]].<ref name="HugdahlWesterhausen2010">{{cite book|author1=Kenneth Hugdahl|author2=René Westerhausen|title=The Two Halves of the Brain: Information Processing in the Cerebral Hemispheres|url=https://books.google.com/books?id=v0RsKYmpe0UC&pg=PA272|year=2010|publisher=MIT Press|isbn=978-0-262-01413-7|pages=272–}}</ref><ref name="Darney1995" /><ref name="pmid14670641k">{{cite journal | vauthors = Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH | title = Classification and pharmacology of progestins | journal = Maturitas | volume = 46 | issue = Suppl 1 | pages = S7–S16 | date = December 2003 | pmid = 14670641 | doi = 10.1016/j.maturitas.2003.09.014 }}</ref> No other progestins have such activity (though some, conversely, possess antiandrogenic activity).<ref name="Darney1995" /><ref name="pmid14670641k" /> Moreover, the androgenic activity of progestins within the testosterone derivatives also varies, and while some may have high or moderate androgenic activity, others have only low or no such activity.<ref name="Golan2008">{{cite book|author=David E. Golan|title=Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy|url=https://books.google.com/books?id=az8uSDkB0mgC&pg=PA520|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-8355-2|pages=520–521}}</ref><ref name="WilliamsFoye2002">{{cite book|author1=David A. Williams|author2=William O. Foye|author3=Thomas L. Lemke|title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=qLJ6Bs1Qml4C&pg=PA700|date=January 2002|publisher=Lippincott Williams & Wilkins|isbn=978-0-683-30737-5|pages=700–}}</ref>

The androgenic activity of androgenic progestins is mediated by two mechanisms: 1) direct binding to and activation of the [[androgen receptor]]; and 2) displacement of [[testosterone]] from [[sex hormone-binding globulin]] (SHBG), thereby increasing free (and thus bioactive) testosterone levels.<ref name="Azziz2007">{{cite book|author=Ricardo Azziz|title=Androgen Excess Disorders in Women|url=https://books.google.com/books?id=Ch-BsGAOtucC&pg=PA124|date=8 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-179-6|pages=124–}}</ref> The androgenic activity of many androgenic progestins is offset by combination with [[ethinylestradiol]], which robustly increases SHBG levels, and most oral contraceptives in fact markedly reduce free testosterone levels and can treat or improve acne and hirsutism.<ref name="Azziz2007" /> An exception is progestin-only contraceptives, which do not also contain an estrogen.<ref name="Azziz2007" />

The relative androgenic activity of testosterone-derivative progestins and other progestins that have androgenic activity can be roughly ranked as follows:

* Very high: [[danazol]], [[ethisterone]], [[gestrinone]], [[normethandrone]], [[norvinisterone]]<ref name="Bentley1980">{{cite book|author=P. J. Bentley|title=Endocrine Pharmacology: Physiological Basis and Therapeutic Applications|url=https://books.google.com/books?id=W6M9AAAAIAAJ&pg=PA4|year=1980|publisher=CUP Archive|isbn=978-0-521-22673-8|pages=4–}}</ref><ref name="Sengupta2007">{{cite book|author=Sengupta|title=Gynaecology For Postgraduate And Practitioners|url=https://books.google.com/books?id=ELkWa34eBz4C&pg=PA137|date=1 January 2007|publisher=Elsevier India|isbn=978-81-312-0436-8|pages=137–}}</ref><ref name="Ferin1962">{{cite journal | vauthors = Ferin J | title = Artificial induction of hypo-oestrogenic amenorrhea with methylestrenolone, or with lynestrenol | journal = Acta Endocrinologica | volume = 39 | issue = 1 | pages = 47–67 | date = January 1962 | pmid = 13892354 | doi = 10.1530/acta.0.0390047 }}</ref><ref name="SaundersDrill1956">{{cite journal | vauthors = Saunders FJ, Drill VA | title = The myotrophic and androgenic effects of 17-ethyl-19-nortestosterone and related compounds | journal = Endocrinology | volume = 58 | issue = 5 | pages = 567–572 | date = May 1956 | pmid = 13317831 | doi = 10.1210/endo-58-5-567 }}</ref>
* High: [[levonorgestrel]], [[norgestrel]], [[norgestrienone]], [[tibolone]]<ref name="Golan2008" /><ref name="WilliamsFoye2002" /><ref name="Bentley1980"/><ref name="LauritzenStudd2005" /><ref name="TashjianArmstrong2011">{{cite book|author1=Armen H. Tashjian|author2=Ehrin J. Armstrong|title=Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy|url=https://books.google.com/books?id=kjCCMZHInigC&pg=PA523|date=21 July 2011|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-1805-6|pages=523–}}</ref><ref name="de GooyerDeckers2003">{{cite journal | vauthors = de Gooyer ME, Deckers GH, Schoonen WG, Verheul HA, Kloosterboer HJ | title = Receptor profiling and endocrine interactions of tibolone | journal = Steroids | volume = 68 | issue = 1 | pages = 21–30 | date = January 2003 | pmid = 12475720 | doi = 10.1016/S0039-128X(02)00112-5 | quote = [Norethisterone] has similar and [norethynodrel] weaker androgenic effects compared to tibolone. | s2cid = 40426061 }}</ref><ref name="pmid16112947t" />
* Moderate: [[norethisterone]] and its [[prodrug]]s ([[norethisterone acetate]], [[norethisterone enanthate]], [[etynodiol diacetate]], [[lynestrenol]], [[quingestanol acetate]])<ref name="pmid3543501">{{cite journal | vauthors = Raynaud JP, Ojasoo T | title = The design and use of sex-steroid antagonists | journal = J. Steroid Biochem. | volume = 25 | issue = 5B | pages = 811–33 | year = 1986 | pmid = 3543501 | doi = 10.1016/0022-4731(86)90313-4| quote = Similar androgenic potential is inherent to norethisterone and its prodrugs (norethisterone acetate, ethynodiol diacetate, lynestrenol, norethynodrel, quingestanol).}}</ref><ref name="Golan2008" /><ref name="WilliamsFoye2002" /><ref name="TashjianArmstrong2011" /><ref name="Chaudhuri2007">{{cite book|author=Chaudhuri|title=Practice Of Fertility Control: A Comprehensive Manual|url=https://books.google.com/books?id=pzanxKlcU74C&pg=PA122|date=1 January 2007|publisher=Elsevier India|isbn=978-81-312-1150-2|pages=122–|edition=7Th}}</ref>
* Low: [[desogestrel]], [[etonogestrel]], [[gestodene]], [[norgestimate]]<ref name="TashjianArmstrong2011" /><ref name="Chaudhuri2007" /><ref name="pmid8808163">{{cite journal | vauthors = Kuhl H | title = Comparative pharmacology of newer progestogens | journal = Drugs | volume = 51 | issue = 2 | pages = 188–215 | year = 1996 | pmid = 8808163 | doi = 10.2165/00003495-199651020-00002| s2cid = 1019532}}</ref>
* Very low or negligible: [[allylestrenol]], [[dimethisterone]], [[medroxyprogesterone acetate]], [[megestrol acetate]], [[norelgestromin]], [[noretynodrel]], [[norgesterone]]<ref name="pmid16112947t" /><ref name="OffermannsRosenthal2008">{{cite book| vauthors = Offermanns S, Rosenthal W |title=Encyclopedia of Molecular Pharmacology|url=https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA391|date=14 August 2008|publisher=Springer Science & Business Media|isbn=978-3-540-38916-3|pages=391–}}</ref><ref name="Marks2001">{{cite book|author=Lara Marks|title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=GgvLA3bqwnoC&pg=PA77|year=2001|publisher=Yale University Press|isbn=978-0-300-08943-1|pages=73–75, 77–78}}</ref><ref name="pmid13753182">{{cite journal | vauthors = Korn GW | title = The use of norethynodrel (enovid) in clinical practice | journal = Canadian Medical Association Journal | volume = 84 | issue = 11 | pages = 584–587 | date = March 1961 | pmid = 13753182 | pmc = 1939348 | quote = Pseudohermaphroditism should not be a problem in these patients as it appears that norethynodrel does not possess androgenic properties, but it is believed that Wilkins has now found one such case in a patient who has been on norethynodrel therapy. }}</ref><ref name="pmid12475720">{{cite journal | vauthors = de Gooyer ME, Deckers GH, Schoonen WG, Verheul HA, Kloosterboer HJ | title = Receptor profiling and endocrine interactions of tibolone | journal = Steroids | volume = 68 | issue = 1 | pages = 21–30 | date = January 2003 | pmid = 12475720 | doi = 10.1016/s0039-128x(02)00112-5 | s2cid = 40426061 }}</ref><ref name="RuggieriMatscher1965">{{cite journal| vauthors = de Ruggieri P, Matscher R, Lupo C, Spazzoli G |title=Biological properties of 17α-vinyl-5(10)-estrene-17β-ol-3-one (norvinodrel) as a progestational and claudogenic compound|journal=Steroids|volume=5|issue=1|year=1965|pages=73–91|issn=0039-128X|doi=10.1016/0039-128X(65)90133-9}}</ref><ref name="SimpsonWeiner1997">{{cite book|author1=J. A. Simpson|author2=E. S. C. Weiner|title=Oxford English Dictionary Additions Series|url=https://books.google.com/books?id=gUGcAQAAQBAJ&pg=PA36|year=1997|publisher=Clarendon Press|isbn=978-0-19-860027-5|pages=36–}}</ref><ref name="JUCKER2013">{{cite book|author=JUCKER|title=Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques|url=https://books.google.com/books?id=BH4ECAAAQBAJ&pg=PA166|date=8 March 2013|publisher=Birkhäuser|isbn=978-3-0348-7053-5|pages=166–}}</ref>
* Antiandrogenic: [[dienogest]], [[oxendolone]]<ref name="AcademicPress1989"/><ref name="pmid16112947t" />

The clinical androgenic and [[anabolic]] activity of the androgenic progestins listed above is still far lower than that of conventional [[androgen]]s and [[anabolic steroid]]s like [[testosterone (medication)|testosterone]] and [[nandrolone ester]]s. As such, they are only generally associated with such effects in women and often only at high doses. In men, due to their concomitant progestogenic activity and by extension antigonadotropic effects, these progestins can have potent functional antiandrogenic effects via suppression of testosterone production and levels.