# Oxendolone

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Oxendolone
> Markdown URL: https://mediated.wiki/source/Oxendolone.md
> Source: https://en.wikipedia.org/wiki/Oxendolone
> Source revision: 1329006125
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical compound}}
{{Distinguish|Oxandrolone}}
{{Drugbox
| Verifiedfields =
| Watchedfields =
| verifiedrevid =
| IUPAC_name = (9''S'',14''S'',17''S'')-16-ethyl-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1''H''-cyclopenta[''a'']phenanthren-3-one
| image = Oxendolone.svg
| image_class = skin-invert-image
| width = 225px

<!--Clinical data-->
| tradename = Prostetin, Roxenone
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA =
| legal_UK =
| legal_US =
| legal_status =
| routes_of_administration = [Intramuscular injection](/source/Intramuscular_injection)<ref name="pmid6131442" /><ref name="pmid26335395" /><ref name="pmid2466359" /><ref name="pmid6419414" />
| class = [Steroidal antiandrogen](/source/Steroidal_antiandrogen); [Progestogen](/source/Progestogen_(medication)); [Progestin](/source/Progestin)

<!--Pharmacokinetic data-->
| bioavailability = [Oral](/source/Oral_administration): Very low (1% in dogs)<ref name="RathboneHadgraft2002" />
| protein_bound =
| metabolism =
| elimination_half-life = {{abbrlink|IM|Intramuscular injection}}: 5.0–6.6&nbsp;days.<ref name="pmid6419414" /><ref name="GaoBohl2005">{{cite journal | vauthors = Gao W, Bohl CE, Dalton JT | title = Chemistry and structural biology of androgen receptor | journal = Chemical Reviews | volume = 105 | issue = 9 | pages = 3352–3370 | date = September 2005 | pmid = 16159155 | pmc = 2096617 | doi = 10.1021/cr020456u }}</ref>
| excretion =

<!--Identifiers-->
| CAS_number_Ref =
| CAS_number = 33765-68-3
| CAS_supplemental =
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = MN4I850D4P
| ATC_prefix =
| ATC_suffix =
| PubChem = 36592
| DrugBank_Ref =
| DrugBank =
| ChemSpiderID_Ref =
| ChemSpiderID = 392001
| synonyms = TSAA-291; 16β-Ethyl-19-nortestosterone; 16β-Ethylestr-4-en-17β-ol-3-one

<!--Chemical data-->
| C=20 | H=30 | O=2
| SMILES = CCC1CC2C3CCC4=CC(=O)CCC4C3CCC2(C1O)C
| StdInChI_Ref =
| StdInChI = 1S/C20H30O2/c1-3-12-11-18-17-6-4-13-10-14(21)5-7-15(13)16(17)8-9-20(18,2)19(12)22/h10,12,15-19,22H,3-9,11H2,1-2H3/t12?,15?,16-,17?,18+,19+,20?/m1/s1
| StdInChIKey_Ref =
| StdInChIKey = FCKLFGKATYPJPG-LNRSQMQGSA-N
}}
<!-- Definition and medical uses -->
'''Oxendolone''', sold under the brand names '''Prostetin''' and '''Roxenone''', is an [antiandrogen](/source/antiandrogen) and [progestin](/source/progestin) medication which is used in [Japan](/source/Japan) in the treatment of [enlarged prostate](/source/benign_prostatic_hyperplasia).<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA914|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=914–}}</ref><ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2935-IA129|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2935–}}</ref><ref name="NegwerScharnow2001">{{cite book| vauthors = Negwer M, Scharnow HG |title=Organic-chemical drugs and their synonyms: (an international survey)|url=https://books.google.com/books?id=zmpqAAAAMAAJ|year=2001|publisher=Wiley-VCH|isbn=978-3-527-30247-5|page=2023}}</ref><ref name="TanLi2014">{{cite journal | vauthors = Tan MH, Li J, Xu HE, Melcher K, Yong EL | title = Androgen receptor: structure, role in prostate cancer and drug discovery | journal = Acta Pharmacologica Sinica | volume = 36 | issue = 1 | pages = 3–23 | date = January 2015 | pmid = 24909511 | pmc = 4571323 | doi = 10.1038/aps.2014.18 }}</ref><ref name="IshizukaNishizawa2002">{{cite journal | vauthors = Ishizuka O, Nishizawa O, Hirao Y, Ohshima S | title = Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy | journal = International Journal of Urology | volume = 9 | issue = 11 | pages = 607–612 | date = November 2002 | pmid = 12534901 | doi = 10.1046/j.1442-2042.2002.00539.x | doi-access = free }}</ref> However, this use is controversial due to concerns about its clinical efficacy.<ref name="IshizukaNishizawa2002" /> Oxendolone is not effective [by mouth](/source/oral_administration) and must be given by [injection into muscle](/source/intramuscular_injection).<ref name="RathboneHadgraft2002" /><ref name="pmid6131442" /><ref name="pmid26335395" /><ref name="pmid2466359" /><ref name="pmid6419414" />

<!-- Side effects and mechanism -->
Oxendolone is an [antiandrogen](/source/antiandrogen), and hence is an [antagonist](/source/receptor_antagonist) of the [androgen receptor](/source/androgen_receptor), the [biological target](/source/biological_target) of androgens like [testosterone](/source/testosterone) and [dihydrotestosterone](/source/dihydrotestosterone).<ref name="AcademicPress1989" /><ref name="Shinogi1991" /><ref name="KirbyChristmas1991" /><ref name="BashirelahiGanesan1986" /><ref name="GaoBohl2005" /> It is also a progestin, or a [synthetic](/source/synthetic_compound) [progestogen](/source/progestogen_(medication)), and hence is an [agonist](/source/agonist) of the [progesterone receptor](/source/progesterone_receptor), the [biological target](/source/biological_target) of progestogens like [progesterone](/source/progesterone).<ref name="AcademicPress1989" /><ref name="Shinogi1991" /><ref name="KirbyChristmas1991" /><ref name="BashirelahiGanesan1986" /> Due to its progestogenic activity, oxendolone has [antigonadotropic](/source/antigonadotropic) effects.<ref name="SudoYamazaki1979" /><ref name="pmid2435122" /> Oxendolone has no other important [hormonal](/source/hormonal_agent) activity...

<!-- History, society, and culture -->
Oxendolone was introduced for medical use in 1981.<ref name="Publishing2013" /> It is used only in Japan.<ref name="Publishing2013" /><ref name="IshizukaNishizawa2002" />

==Medical uses==
Oxendolone is used in the treatment of [benign prostatic hyperplasia](/source/benign_prostatic_hyperplasia) (BPH) in [Japan](/source/Japan).<ref name="Publishing2013" /><ref name="IshizukaNishizawa2002" /> It has been used at a dosage of 200&nbsp;mg once every 2&nbsp;weeks via [intramuscular injection](/source/intramuscular_injection).<ref name="pmid2435122">{{cite journal | vauthors = Katayama T, Umeda K, Kazama T | title = [Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy] | language = ja | journal = Hinyokika Kiyo. Acta Urologica Japonica | volume = 32 | issue = 11 | pages = 1584–1589 | date = November 1986 | pmid = 2435122 }}</ref> Although it is approved for the treatment of BPH in Japan, concerns have been raised about its use for this condition due to poor efficacy seen in [clinical trial](/source/clinical_trial)s.<ref name="IshizukaNishizawa2002" />

==Side effects==
{{See also|Antiandrogen#Side effects|Progestin#Side effects}}

==Pharmacology==

===Pharmacodynamics===
Oxendolone binds to the [androgen receptor](/source/androgen_receptor) (K<sub>i</sub> = 320&nbsp;nM) and [progesterone receptor](/source/progesterone_receptor) (K<sub>i</sub> = 20&nbsp;nM) and acts as a weak but clinically relevant [inhibitor](/source/enzyme_inhibitor) of [5α-reductase](/source/5%CE%B1-reductase) ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 1.4&nbsp;μM).<ref name="AcademicPress1989">{{cite book | vauthors = Mallamo JP, Juniewicz PE | chapter = New horizons in the treatment of proliferative prostatic disease | veditors = Johns WS |title=Annual Reports in Medicinal Chemistry | chapter-url = https://books.google.com/books?id=HrALiG-4t7UC&pg=PA199 |date=8 September 1989| volume = 24 |publisher=Academic Press|isbn=978-0-08-058368-6|pages=199– | doi = 10.1016/S0065-7743(08)60543-6 }}</ref><ref name="Shinogi1991">{{cite book|title=Annual report of Shionogi Research Laboratories|url=https://books.google.com/books?id=kR40AAAAIAAJ|year=1991|pages=76–77}}</ref><ref name="KirbyChristmas1991">{{cite journal| vauthors = Kirby RS, Christmas T |title=The potential value of 5-alpha-reductase inhibition in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia|journal=World Journal of Urology|volume=9|issue=1|year=1991|issn=0724-4983|doi=10.1007/BF00184713|s2cid=38790542}}</ref><ref name="BashirelahiGanesan1986">{{cite journal | vauthors = Bashirelahi N, Ganesan S, Ekiko DB, Young JD, Shida K, Yamanaka H, Takahashi E | title = Effect of 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291) on the binding of promegestone (R5020) and methyltrienolone (R1881) to hyperplastic and neoplastic human prostate | journal = Journal of Steroid Biochemistry | volume = 25 | issue = 3 | pages = 367–374 | date = September 1986 | pmid = 2430141 | doi = 10.1016/0022-4731(86)90249-9 }}</ref> The [relative binding affinity](/source/relative_binding_affinity) of oxendolone for the androgen receptor is 0.8 to 3.6% of that of [metribolone](/source/metribolone).<ref name="DaltonGao2010">{{cite book | vauthors = Dalton J, Gao W | chapter = Androgen Receptor|year=2010|pages=143–182|doi=10.1007/978-90-481-3303-1_6| title = Nuclear Receptors: Current Concepts and Future Challenges | series = Proteins and Cell Regulation| publisher = Springer|isbn=978-90-481-3302-4}}</ref><ref name="pmid7339263">{{cite journal | vauthors = Wakeling AE, Furr BJ, Glen AT, Hughes LR | title = Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens | journal = Journal of Steroid Biochemistry | volume = 15 | pages = 355–359 | date = December 1981 | pmid = 7339263 | doi = 10.1016/0022-4731(81)90297-1 }}</ref> Oxendolone is not a [silent antagonist](/source/silent_antagonist) of the androgen receptor but is rather predominantly antagonistic with weak [agonist](/source/agonist)ic activity;<ref name="Shinogi1991" /> for this reason, it has been described as a [selective androgen receptor modulator](/source/selective_androgen_receptor_modulator).<ref name="HikichiYamaoka2015">{{cite journal | vauthors = Hikichi Y, Yamaoka M, Kusaka M, Hara T | title = Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile | journal = European Journal of Pharmacology | volume = 765 | pages = 322–331 | date = October 2015 | pmid = 26335395 | doi = 10.1016/j.ejphar.2015.08.052 }}</ref> The medication has potent [antigonadotropic](/source/antigonadotropic) effects via its progestogenic activity.<ref name="SudoYamazaki1979">{{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 Endocrinologica. Supplementum | volume = 229 | issue = 3 Supplb | pages = 53–66 | year = 1979 | pmid = 294107 | doi = 10.1530/acta.0.092S053 }}</ref> It has been found to suppress [luteinizing hormone](/source/luteinizing_hormone) and [testosterone](/source/testosterone) levels to an equivalent extent as [allylestrenol](/source/allylestrenol) and [chlormadinone acetate](/source/chlormadinone_acetate), which are two progestins that are similarly used at high doses to treat BPH.<ref name="pmid2435122" />

===Pharmacokinetics===
The [oral](/source/oral_administration) [bioavailability](/source/bioavailability) of oxendolone in dogs is extremely low, 1% at most.<ref name="RathboneHadgraft2002">{{cite book| vauthors = Iga K | chapter = Slowly Disintegrating Buccal Mucoadhesive Pain-Tablet (S-DBMP-T) and Buccal Covered=Tablet System (BCTS) | veditors = Rathbone MJ, Hadgraft J, Roberts MS |title=Modified-Release Drug Delivery Technology | chapter-url = https://books.google.com/books?id=mw9W82MLYZ8C&pg=PA368 |date=7 November 2002|publisher=CRC Press|isbn=978-0-8247-0869-6|pages=368–}}</ref> Due to its low oral bioavailability, oxendolone is administered by [intramuscular injection](/source/intramuscular_injection) in humans.<ref name="pmid6131442">{{cite journal | vauthors = Henkler G, Klotzbach M, Koch H, Müller W, Richter J | title = [Progress in the area of drug development. 15] | language = de | journal = Die Pharmazie | volume = 37 | issue = 11 | pages = 753–765 | date = November 1982 | pmid = 6131442 | quote = [Oxendolone] has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy. }}</ref><ref name="pmid26335395">{{cite journal | vauthors = Hikichi Y, Yamaoka M, Kusaka M, Hara T | title = Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile | journal = European Journal of Pharmacology | volume = 765 | pages = 322–331 | date = October 2015 | pmid = 26335395 | doi = 10.1016/j.ejphar.2015.08.052 | quote = According to the clinical data of TSAA-291, the plasma level of TSAA-291 after weekly intramuscular administration at 400 mg/kg for 12 weeks is approximately 100 nM (Drug Information). }}</ref><ref name="pmid2466359">{{cite journal | vauthors = Ostri P, Swartz R, Meyhoff HH, Petersen JH, Lindgård G, Frimodt-Møller C, Andersson T, Nielsen MS | display-authors = 6 | title = Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial | journal = Urological Research | volume = 17 | issue = 1 | pages = 29–33 | year = 1989 | pmid = 2466359 | doi = 10.1007/bf00261046 | quote = Thirty patients were treated with weekly injections of oxendolone 200 mg during a 3 months' period, and 30 patients were allocated to placebo treatment. | s2cid = 30551043 }}</ref><ref name="pmid6419414">{{cite journal | vauthors = Midgley I, Fowkes AG, Darragh A, Lambe R, Chasseaud LF, Taylor T | title = The metabolic fate of the anti-androgenic agent, oxendolone, in man | journal = Steroids | volume = 41 | issue = 4 | pages = 521–536 | date = April 1983 | pmid = 6419414 | doi = 10.1016/0039-128x(83)90092-2 | quote = After intramuscular administration of 16β-ethyl-17β-hydroxy-4-[4-14C] estren-3-one (14C-oxendolone; 300 mg) to 3 human subjects, [...] | s2cid = 41224726 }}</ref> Its [elimination half-life](/source/elimination_half-life) via this route is 5.0 to 6.6&nbsp;days.<ref name="pmid6419414" />

==Chemistry==
{{See also|List of progestogens|Steroidal antiandrogen|List of steroidal antiandrogens}}

Oxendolone, also known as 16β-ethyl-19-nortestosterone or 16β-ethylestr-4-en-17β-ol-3-one, is a [synthetic](/source/synthetic_compound) [estrane](/source/estrane) [steroid](/source/steroid) and a [derivative](/source/chemical_derivative) of [testosterone](/source/testosterone_(medication)) and [19-nortestosterone](/source/19-nortestosterone) (nandrolone).<ref name="Elks2014" /><ref name="Publishing2013" />

The [acetate](/source/acetate) [ester](/source/ester) of oxendolone is known as TSAA-328, while the [caproate](/source/caproate) ester of oxendolone is known as TSAA-330.<ref name="pmid294106">{{cite journal | vauthors = Masuoka M, Masaki T, Yamazaki I, Hori T, Nakayama R | title = Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives | journal = Acta Endocrinologica. Supplementum | volume = 229 | pages = 36–52 | year = 1979 | pmid = 294106 | doi = 10.1530/acta.0.092s036 }}</ref> They were never marketed.<ref name="pmid294106" />

==History==
Oxendolone has been marketed in [Japan](/source/Japan) by [Takeda](/source/Takeda_Pharmaceutical_Company) since 1981.<ref name="Publishing2013" />

==Society and culture==

===Generic names===
''Oxendolone'' is the [generic name](/source/generic_term) of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014" /><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/oxendolone.html|title=Oxandrolone Uses, Side Effects & Warnings | work = Drugs.com }}</ref> It is also known by its developmental code name ''TSAA-291''.<ref name="Elks2014" /><ref name="Drugs.com" />

===Brand names===
Oxendolone is or has been sold under the brand names Prostetin and Roxenone.<ref name="Elks2014" /><ref name="Drugs.com" />

===Availability===
Oxendolone is marketed only in [Japan](/source/Japan).<ref name="Drugs.com" />

== References ==
{{Reflist}}

{{Navboxes
| title = [Medical uses](/source/Medicine)
| titlestyle = background:#ccccff
| list1 =
{{Androgens and antiandrogens}}
{{Progestogens and antiprogestogens}}
{{Drugs used in benign prostatic hypertrophy}}
}}
{{Navboxes
| title = [Pharmacodynamics](/source/Pharmacodynamics)
| titlestyle = background:#ccccff
| list1 =
{{Androgen receptor modulators}}
{{Progesterone receptor modulators}}
}}

Category:5α-Reductase inhibitors
Category:Secondary alcohols
Category:Antigonadotropins
Category:Drugs for benign prostatic hyperplasia
Category:Estranes
Category:Ketones
Category:Progestogens
Category:Steroidal antiandrogens

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Adapted from the Wikipedia article [Oxendolone](https://en.wikipedia.org/wiki/Oxendolone) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Oxendolone?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.