Methyltestosteroneのソースを表示

{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc}}
<nowiki></nowiki>{{Redirect|Android (drug)|the drug used in the treatment of anemia|Androyd}}
{{Infobox drug
| Verifiedfields     = verified
| Watchedfields      = verified
| verifiedrevid      = 434903709
| IUPAC_name         = (8''R'',9''S'',10''R'',13''S'',14''S'',17''S'')-17-hydroxy-10,13,17-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1''H''-cyclopenta[''a'']phenanthren-3-one
| image              = Methyltestosterone.svg
| image_class        = skin-invert-image
| width              = 225px
| image2             = Methyltestosterone molecule ball.png
| width2             = 235px

<!--Clinical data-->| tradename          = Agoviron, Android, Metandren, Oraviron, Oreton, Testovis, Testred, Virilon, others
| Drugs.com          = {{drugs.com|monograph|methyltestosterone}}
| pregnancy_AU       = D
| pregnancy_US       = X
| pregnancy_category = 
| legal_BR = C5
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA           = Schedule IV
| legal_US           = Schedule III
| legal_AU           = Schedule 4
| legal_status       = Rx-only
| routes_of_administration = [[Oral administration|By mouth]], [[buccal administration|buccal]], [[sublingual administration|sublingual]]<ref name="Llewellyn2009" /><ref name="Ebadi2007" /><ref name="Hohl2017" />
| class              = [[Androgen]]; [[Anabolic steroid]]

<!--Pharmacokinetic data-->| protein_bound      = 98%<ref name="WooRobinson2015" />
| bioavailability    = ~70%<ref name="LemkeWilliams2012" />
| metabolism         = [[Liver]]
| elimination_half-life = 150 minutes (~2.5–3 hours)<ref name="LemkeWilliams2012" /><ref name="BehreWang2004">{{cite book| vauthors = Behre HM, Wang C, Handelsman DJ, Nieschlag E |title=Testosterone |chapter=Pharmacology of testosterone preparations|year=2004|pages=405–444|doi=10.1017/CBO9780511545221.015|isbn=978-0-511-54522-1}}</ref>
| duration_of_action = 1–3 days<ref name="WooRobinson2015" />
| excretion          = [[Urine]]: 90%<ref name="WooRobinson2015" /><br />[[Feces]]: 6%<ref name="WooRobinson2015" /><ref name="Saeb-Parsy1999" />

<!--Identifiers-->| IUPHAR_ligand      = 6945
| CAS_number_Ref     = {{cascite|correct|CAS}}
| CAS_number         = 58-18-4
| ATC_prefix         = G03
| ATC_suffix         = BA02
| ATC_supplemental   = {{ATC|G03|EK01}}
| PubChem            = 6010
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB06710
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 5788
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = V9EFU16ZIF
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 6892
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| ChEMBL             = 1395
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00408
| synonyms           = RU-24400; NSC-9701; 17α-Methyltestosterone; 17α-Methylandrost-4-en-17β-ol-3-one<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" />

<!--Chemical data-->| C                  = 20
| H                  = 30
| O                  = 2
| SMILES             = C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@]4(C)O)C
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C20H30O2/c1-18-9-6-14(21)12-13(18)4-5-15-16(18)7-10-19(2)17(15)8-11-20(19,3)22/h12,15-17,22H,4-11H2,1-3H3/t15-,16+,17+,18+,19+,20+/m1/s1
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = GCKMFJBGXUYNAG-HLXURNFRSA-N
}}
<!-- Definition and medical uses -->
'''Methyltestosterone''', sold under the brand names '''Android''', '''Metandren''', and '''Testred''' among others, is an [[androgen]] and [[anabolic steroid]] (AAS) medication which is used in the treatment of [[hypogonadism|low testosterone levels]] in men, [[delayed puberty]] in boys, at low doses as a component of [[menopausal hormone therapy]] for [[menopause|menopausal]] [[symptom]]s like [[hot flash]]es, [[osteoporosis]], and [[hypoactive sexual desire disorder|low sexual desire]] in women, and to treat [[breast cancer]] in women.<ref name="Llewellyn2009">{{cite book| vauthors = Llewellyn W |title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC|year=2009|publisher=Molecular Nutrition Llc|isbn=978-0-9679304-7-3|pages=16,19,22,27,30,36,39,42,46,291–293}}</ref><ref name="Ebadi2007">{{cite book| vauthors = Ebadi M |title=Desk Reference of Clinical Pharmacology, Second Edition|url=https://books.google.com/books?id=ihxyHbnj3qYC&pg=PA434|date=31 October 2007|publisher=CRC Press|isbn=978-1-4200-4744-8|pages=434–}}</ref><ref name="YagielaDowd2010">{{cite book | vauthors = Yagiela JA, Dowd FJ, Johnson B, Mariotti A, Neidle EA |title= Pharmacology and Therapeutics for Dentistry - E-Book|url=https://books.google.com/books?id=utVOHYuhxioC&pg=PA569 |date= 19 March 2010 |publisher= Elsevier Health Sciences|isbn=978-0-323-07824-5|pages=569–}}</ref><ref name="Android-Label" /><ref name="EE-MT-Label" /> It is taken [[oral administration|by mouth]] or held [[buccal administration|in the cheek]] or [[sublingual administration|under the tongue]].<ref name="Llewellyn2009" /><ref name="Android-Label" /><ref name="EE-MT-Label" /><ref name="Hohl2017">{{cite book| vauthors = Kalinchenko S, Tyuzikov I, Mskhalaya G, Tishova Y | chapter = Testosterone Therapy: Oral Androgens | veditors = Hohl A |title=Testosterone: From Basic to Clinical Aspects|chapter-url=https://books.google.com/books?id=Et6TDgAAQBAJ&pg=PA205|date=30 March 2017|publisher=Springer|isbn=978-3-319-46086-4|pages=204–205}}</ref>

<!-- Side effects and mechanism of action -->
[[Side effect]]s of methyltestosterone include [[symptom]]s of [[virilization|masculinization]] like [[acne]], [[hirsutism|increased hair growth]], [[voice deepening|voice changes]], and increased [[libido|sexual desire]].<ref name="Llewellyn2009" /> It can also cause [[estrogen (medication)|estrogen]]ic effects like [[water retention (medicine)|fluid retention]], [[breast tenderness]], and [[gynecomastia|breast enlargement]] in men and [[hepatotoxicity|liver damage]].<ref name="Llewellyn2009" /> The drug is a [[synthetic compound|synthetic]] androgen and anabolic steroid and hence is an [[agonist]] of the [[androgen receptor]] (AR), the [[biological target]] of androgens like [[testosterone]] and [[dihydrotestosterone]] (DHT).<ref name="Llewellyn2009" /><ref name="pmid18500378">{{cite journal | vauthors = Kicman AT | title = Pharmacology of anabolic steroids | journal = Br. J. Pharmacol. | volume = 154 | issue = 3 | pages = 502–21 | year = 2008 | pmid = 18500378 | pmc = 2439524 | doi = 10.1038/bjp.2008.165 }}</ref> It has moderate [[androgen]]ic effects and moderate [[anabolic]] effects, which make it useful for producing masculinization.<ref name="Llewellyn2009" /><ref name="Kochakian2012">{{cite book| vauthors = Potts GO, Arnold A, Beyler AL | chapter = Dissociation of the androgenic and other hormonal activities from the protein anabolic effects of steroids | veditors = Kochakian CD |title=Anabolic-Androgenic Steroids| chapter-url=https://books.google.com/books?id=3-LrCAAAQBAJ&pg=PA401|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-66353-6 | doi = 10.1007/978-3-642-66353-6_11 |pages=13,401,454}}</ref>

<!-- History, society, and culture -->
Methyltestosterone was discovered in 1935 and was introduced for medical use in 1936.<ref name="Hohl2017" /><ref name="ThiemeHemmersbach2009">{{cite book | vauthors = Thieme D, Hemmersbach P |title=Doping in Sports |url= https://books.google.com/books?id=R-hIC-caIn8C&pg=PA101 |date=18 December 2009 |publisher=Springer Science & Business Media |isbn=978-3-540-79088-4 |pages=101, 470}}</ref><ref name="pmid11589254" /><ref name="NARD1956" /><ref name="Llewellyn2009" /> It was [[chemical synthesis|made]] shortly after the discovery of [[testosterone]] and was one of the first synthetic AAS to be developed.<ref name="Hohl2017" /><ref name="ThiemeHemmersbach2009" /><ref name="pmid11589254" /> In addition to its medical use, methyltestosterone is used to [[performance-enhancing substance|improve physique and performance]], although it is not as commonly used as other AAS for such purposes due to its androgenic effects, estrogenic effects, and risk of liver damage.<ref name="Llewellyn2009" /> The drug is a [[controlled substance]] in many countries and so non-medical use is generally illicit.<ref name="Llewellyn2009" />
{{TOC limit}}

==Uses==

===Medical===
Methyltestosterone is or has been used in the treatment of [[delayed puberty]], [[hypogonadism]], [[cryptorchidism]], and [[erectile dysfunction]] in males, and in low doses to treat [[menopause|menopausal symptom]]s (specifically for [[osteoporosis]], [[hot flash]]es, and to increase [[libido]] and [[energy (psychological)|energy]]), [[postpartum]] [[breast pain]] and [[breast engorgement|engorgement]], and [[breast cancer]] in women.<ref name="Llewellyn2009" /><ref name="Ebadi2007"/><ref name="YagielaDowd2010"/> It is specifically approved in the [[United States]] for the treatment of hypogonadism and delayed puberty in males and the treatment of advanced inoperable breast cancer in females.<ref name="Android-Label">{{cite web | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/083976s031lbl.pdf | title = Android® C-III, Brand of Methyl TESTOSTERone | work = Valeant Pharmaceuticals North America | publisher = U.S. Food and Drug Administration }}</ref> It was also approved in low doses [[esterified estrogens/methyltestosterone|in combination with esterified estrogens]] for the treatment of moderate to severe [[vasomotor]] [[symptom]]s associated with [[menopause]] in women in the United States, but this formulation was discontinued and hence is no longer used.<ref name="EE-MT-Label">{{Cite web | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5845e789-8191-46f9-bbd0-79fb0c716601 | work = DailyMed | publisher = U.S. National Library of Medicine | title = Esterified estrogens and methyltestosterone tablet, film coated }}</ref>

Methyltestosterone is less effective in inducing masculinization than testosterone, but is useful for maintaining established masculinization in adults.<ref name="ThomasKeenan2012">{{cite book| vauthors = Thomas JA, Keenan EJ |title=Principles of Endocrine Pharmacology|url=https://books.google.com/books?id=mTagBQAAQBAJ&pg=PA125|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4684-5036-1|pages=125–}}</ref>

The dosages of methyltestosterone used are 10 to 50&nbsp;mg/day in men for common medical uses like hypogonadism and delayed puberty as well as physique- and performance-enhancing purposes and 2.5&nbsp;mg/day in women for menopausal symptoms.<ref name="Llewellyn2009" /> Higher dosages of 50 to 200&nbsp;mg/day have been used to treat women with inoperable breast cancer that has failed to respond to other therapies, although such dosages are associated with severe irreversible virilization.<ref name="Llewellyn2009" />

{{Androgen replacement therapy formulations and dosages used in men}}

{{Androgen replacement therapy formulations and dosages used in women}}

{{Androgen/anabolic steroid dosages for breast cancer}}

===Non-medical===
Methyltestosterone is used for [[performance-enhancing drug|physique- and performance-enhancing purpose]]s by [[competition|competitive]] [[athlete]]s, [[bodybuilder]]s, and [[powerlifter]]s, although it is not commonly used relative to other AAS for such purposes.<ref name="Llewellyn2009" />

===Available forms===
{{See also|Esterified estrogens/methyltestosterone|Conjugated estrogens/methyltestosterone}}

Methyltestosterone is typically used as an oral medication.<ref name="Hohl2017" /> It is also available under the brand names Metandren and Oreton Methyl for use specifically by [[buccal administration|buccal]] or [[sublingual administration]].<ref name="Hohl2017" /><ref name="AMA1983">{{cite book|author1=American Medical Association. Division of Drugs|author2=American Society for Clinical Pharmacology and Therapeutics|chapter=Androgens and Anabolic Steroids|pages=[https://archive.org/details/amadrugevaluatio0005amer/page/913 913]–930|title=AMA Drug Evaluations|url=https://archive.org/details/amadrugevaluatio0005amer|url-access=registration|year=1983|publisher=American Medical Association|isbn=978-0-89970-160-8}}</ref> Methyltestosterone is available in the form of 2, 5, 10, and 25&nbsp;mg oral tablets.<ref name="Lorrain1994">{{cite book | vauthors = Plouffe Jr L, Cohen DP | chapter = The Role of Androgens in Menopausal Hormone | veditors = Lorrain J |title=Comprehensive Management of Menopause| chapter-url = https://books.google.com/books?id=8MwuUkPE5WgC&pg=PA301 |year=1994|publisher=Springer Science & Business Media|isbn=978-0-387-97972-4 | doi = 10.1007/978-1-4612-4330-4_28 |pages=301–}}</ref><ref name="Kahr2013">{{cite book| vauthors = Kahr H |title=Konservative Therapie der Frauenkrankheiten: Anzeigen, Grenzen und Methoden Einschliesslich der Rezeptur|url=https://books.google.com/books?id=Hte1BgAAQBAJ&pg=PA21|date=8 March 2013|publisher=Springer-Verlag|isbn=978-3-7091-5694-0|pages=21–}}</ref> It was also available in combination with estrogens as [[esterified estrogens/methyltestosterone]] (0.625&nbsp;mg/1.25&nbsp;mg, 1.25&nbsp;mg/2.5&nbsp;mg) and [[conjugated estrogens/methyltestosterone]] (0.625&nbsp;mg/5.0&nbsp;mg, 1.25&nbsp;mg/10&nbsp;mg).<ref name="Lorrain1994" />

==Contraindications==
Methyltestosterone should be used with caution in women and children, as it can cause irreversible virilization.<ref name="Llewellyn2009" /> Due to its estrogenicity, methyltestosterone can also accelerate [[epiphyseal closure]] and thereby produce [[short stature]] in children and adolescents.<ref name="Llewellyn2009" /> It can worsen symptoms in men with [[benign prostatic hyperplasia]].<ref name="Llewellyn2009" /> Methyltestosterone should not be used in men with [[prostate cancer]], as androgens can accelerate [[tumor progression]].<ref name="Llewellyn2009" /> The drug should be used with caution in patients with pre-existing [[hepatotoxicity]], due to its own potential for hepatotoxicity.<ref name="Llewellyn2009" />

==Side effects==
{{See also|Anabolic steroid#Adverse effects}}

[[Adverse effect]]s of methyltestosterone include [[androgen]]ic side effects like [[oily skin]], [[acne]], [[seborrhea]], increased [[facial hair|facial]]/[[body hair]] [[hair growth|growth]], [[pattern hair loss|scalp hair loss]], increased [[aggressiveness]] and [[sex drive]], and [[spontaneous erection]]s, as well as [[estrogen (medication)|estrogen]]ic side effects like [[breast tenderness]], [[gynecomastia]], [[water retention (medicine)|fluid retention]], and [[edema]].<ref name="Llewellyn2009" /><ref name="Kicman2008" /> In women, methyltestosterone can cause partially irreversible [[virilization]], for instance [[voice deepening]], [[hirsutism]], [[clitoromegaly]], [[breast atrophy]], and [[muscle hypertrophy]], as well as [[menstrual irregularity|menstrual disturbance]]s and reversible [[infertility]].<ref name="Llewellyn2009" /><ref name="Kicman2008" /> In men, the drug may also cause [[hypogonadism]], [[testicular atrophy]], and reversible infertility at sufficiently high dosages.<ref name="Llewellyn2009" /><ref name="Kicman2008" />

Methyltestosterone can sometimes cause [[hepatotoxicity]], for instance [[elevated liver enzymes]], [[cholestatic jaundice]], [[peliosis hepatis]], [[hepatoma]]s, and [[hepatocellular carcinoma]], with extended use.<ref name="Llewellyn2009" /><ref name="Kicman2008" /><ref name="Aronson2009">{{cite book| vauthors = Aronson JK | chapter = Androgens and Anabolic Steroids |title=Meyler's Side Effects of Endocrine and Metabolic Drugs|chapter-url=https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA141|date=21 February 2009|publisher=Elsevier|isbn=978-0-08-093292-7|pages=141–}}</ref> It can also have adverse effects on the [[cardiovascular system]].<ref name="Llewellyn2009" /> AAS like methyltestosterone stimulate [[erythropoiesis]] ([[red blood cell]] production) and increase [[hematocrit]] levels and at high dosages can cause [[polycythemia]] (overproduction of red blood cells), which can greatly increase the risk of [[thrombosis|thrombic]] events such as [[embolism]] and [[stroke]].<ref name="Llewellyn2009" /> With long-term treatment, AAS can increase the risk of [[benign prostatic hyperplasia]] and [[prostate cancer]].<ref name="Llewellyn2009" /> [[Violence|Violent]] and even [[homicide|homicidal behavior]], [[hypomania]]/[[mania]], [[depression (mood)|depression]], [[suicidality]], [[delusion]]s, and [[psychosis]] have all been associated with very high dosages of AAS.<ref name="SadockSadock2011">{{cite book| vauthors = Sadock BJ, Sadock VA |title=Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry|url=https://books.google.com/books?id=fFi7DR2hmaIC|date=26 December 2011|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-7861-6}}</ref>

==Interactions==
[[Aromatase inhibitor]]s can be used to reduce or prevent the [[estrogen (medication)|estrogen]]ic effects of methyltestosterone and [[5α-reductase inhibitor]]s can be used to reduce its virilizing effects and thereby improve its ratio of [[anabolic]] to [[androgen]]ic activity and reduce its rate of androgenic [[side effect]]s.<ref name="Llewellyn2009" />

==Pharmacology==

===Pharmacodynamics===
{{Relative androgenic to anabolic activity in animals}}

As an AAS, methyltestosterone is an [[agonist]] of the [[androgen receptor]] (AR), similarly to [[androgen]]s like [[testosterone]] and [[dihydrotestosterone]] (DHT).<ref name="Llewellyn2009" /><ref name="Kicman2008">{{cite journal | vauthors = Kicman AT | title = Pharmacology of anabolic steroids | journal = British Journal of Pharmacology | volume = 154 | issue = 3 | pages = 502–521 | date = June 2008 | pmid = 18500378 | pmc = 2439524 | doi = 10.1038/bjp.2008.165 }}</ref> It is a [[substrate (biochemistry)|substrate]] for [[5α-reductase]] like testosterone, and so is potentiated analogously in so-called "androgenic" tissues like the [[skin]], [[hair follicle]]s, and [[prostate gland]] via [[biotransformation|transformation]] into the more [[potency (pharmacology)|potent]] AR agonist [[mestanolone]] (17α-methyl-DHT).<ref name="Llewellyn2009" /><ref name="Kicman2008" /> As such, methyltestosterone has a relatively low ratio of [[anabolic]] to [[androgen]]ic activity, with a similar ratio to that of testosterone (close to 1:1), and this makes it among the most androgenic AAS.<ref name="Llewellyn2009" /><ref name="Kicman2008" /> Due to efficient [[aromatization]] into the potent and [[metabolic stability|metabolism-resistant]] [[estrogen (medication)|estrogen]] [[methylestradiol]] (17α-methylestradiol), methyltestosterone has relatively high [[estrogen]]icity and hence potential for [[estrogen (medication)|estrogen]]ic [[side effect]]s such as [[gynecomastia]] and [[water retention (medicine)|fluid retention]].<ref name="ThiemeHemmersbach2009" /><ref name="Genazzani2006">{{cite book| vauthors = Genazzani AR |title=Postmenopausal Osteoporosis: Hormones & Other Therapies|url=https://books.google.com/books?id=P7tzqD9J7TgC&pg=PA243|date=17 January 2006|publisher=Taylor & Francis US|isbn=978-1-84214-311-7|pages=243–}}</ref> The drug possesses negligible [[progestogen]]ic activity.<ref name="Llewellyn2009" /><ref name="Kicman2008" />

Due to its combined disadvantages of a relatively poor ratio of anabolic to androgenic activity, unusually high estrogenicity, and the potential for [[hepatotoxicity]] (as with other 17α-alkylated AAS), methyltestosterone has not been used as commonly as many other AAS either in medicine or for physique- or performance-enhancing purposes.<ref name="Llewellyn2009" />

===Pharmacokinetics===

====Absorption====
Methyltestosterone has dramatically improved [[oral administration|oral]] [[bioavailability]] and [[metabolic stability]] relative to testosterone.<ref name="Llewellyn2009" /><ref name="Kicman2008" /> This difference is due to the C17α methyl group, which results in [[steric hindrance]] and prevents [[metabolism]].<ref name="Llewellyn2009" /><ref name="Kicman2008" /> The oral bioavailability of methyltestosterone is about 70%, and it is [[absorption (pharmacokinetics)|well-absorbed]] from the [[gastrointestinal tract]].<ref name="LemkeWilliams2012">{{cite book | vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1360|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=1360–}}</ref> Methyltestosterone can also be taken [[buccal administration|buccally]] or [[sublingual administration|sublingually]].<ref name="Llewellyn2009" /><ref name="LemkeWilliams2012" /> Although effective orally, methyltestosterone is more effective by these non-oral routes, which are said to approximately double its bioavailability and require half the oral dosage.<ref name="Llewellyn2009" /><ref name="LemkeWilliams2012" /><ref name="AMA1983" />

Circulating levels of methyltestosterone with administration of 1.25 to 2.5&nbsp;mg/day oral methyltestosterone in women are in the range of 20 to 30&nbsp;ng/dL.<ref name="Lobo2001">{{cite journal | vauthors = Lobo RA | title = Androgens in postmenopausal women: production, possible role, and replacement options | journal = Obstetrical & Gynecological Survey | volume = 56 | issue = 6 | pages = 361–376 | date = June 2001 | pmid = 11466487 | doi = 10.1097/00006254-200106000-00022 | s2cid = 9872335 }}</ref> For comparison to testosterone, methyltestosterone is at least as potent as an AAS.<ref name="Lobo2001" /> However, due to the large decrease in [[sex hormone-binding globulin]] (SHBG) levels and hence increase in free unbound testosterone caused by methyltestosterone, androgenic effects may be greater than reflected merely by methyltestosterone levels.<ref name="Lobo2001" />

====Distribution====
Methyltestosterone is highly [[plasma protein binding|protein-bound]], by approximately 98%.<ref name="WooRobinson2015" /> The medication has low but significant [[affinity (pharmacology)|affinity]] for human serum [[sex hormone-binding globulin]] (SHBG), about 25% of that of testosterone and 5% of that of DHT.<ref name="Llewellyn2009" /><ref name="pmid6539197">{{cite journal | vauthors = Saartok T, Dahlberg E, Gustafsson JA | title = Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin | journal = Endocrinology | volume = 114 | issue = 6 | pages = 2100–6 | year = 1984 | pmid = 6539197 | doi = 10.1210/endo-114-6-2100 }}</ref>

====Metabolism====
The [[biological half-life]] of methyltestosterone is approximately 3&nbsp;hours (range 2.5–3.5&nbsp;hours).<ref name="LemkeWilliams2012" /><ref name="Saeb-Parsy1999">{{cite book| vauthors = Saeb-Parsy K |title=Instant Pharmacology|url=https://books.google.com/books?id=F4-IdTewurIC&pg=PA260|date=18 June 1999|publisher=John Wiley & Sons|isbn=978-0-471-97639-4|pages=260–}}</ref> The [[duration of action]] of methyltestosterone is said to be 1 to 3&nbsp;days, and is described as relatively short among AAS.<ref name="WooRobinson2015">{{cite book | vauthors = Woo TM, Robinson MV |title=Pharmacotherapeutics For Advanced Practice Nurse Prescribers|url=https://books.google.com/books?id=2Q5hCgAAQBAJ&pg=PA618|date=3 August 2015|publisher=F.A. Davis|isbn=978-0-8036-4581-3|pages=618–}}</ref><ref name="CrespoWecker2009">{{cite book | vauthors = Crespo L, Wecker L, Dunaway G, Faingold C, Watts S |title= Brody's Human Pharmacology - E-Book|url=https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA469|date=1 April 2009|publisher=Elsevier Health Sciences|isbn=978-0-323-07575-6|pages=469–}}</ref>

====Excretion====
Methyltestosterone is [[excretion|excreted]] 90% in the [[urine]] as [[conjugate (biochemistry)|conjugate]]s and other [[metabolite]]s, and 6% in [[feces]].<ref name="WooRobinson2015" />

==Chemistry==
{{See also|List of androgens/anabolic steroids#Testosterone derivatives}}

Methyltestosterone, also known as 17α-methyltestosterone or as 17α-methylandrost-4-en-17β-ol-3-one, is a [[synthetic compound|synthetic]], [[17α-alkylated anabolic steroid|17α-alkylated]] [[androstane]] [[steroid]] and a [[chemical derivative|derivative]] of testosterone differing from it only in the presence of a methyl group at the C17α position.<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=PA653|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=653–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA676|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=676–}}</ref><ref name="Llewellyn2009" /> Close synthetic relatives of methyltestosterone include [[metandienone]] (17α-methyl-δ<sup>1</sup>-testosterone) and [[fluoxymesterone]] (9α-fluoro-11β-hydroxy-17α-methyltestosterone).<ref name="Llewellyn2009" /><ref name="Kicman2008" />

===Derivatives===
{{See also|17α-Alkylated anabolic steroid#List of 17α-alkylated AAS}}

Methyltestosterone and [[ethyltestosterone]] (17α-ethyltestosterone) are the [[parent structure]]s of all 17α-alkylated AAS. Major 17α-alkylated AAS include the testosterone derivatives [[fluoxymesterone]], [[metandienone]] (methandrostenolone), and methyltestosterone and the DHT derivatives [[oxandrolone]], [[oxymetholone]], and [[stanozolol]].<ref name="Llewellyn2009" /><ref name="Kicman2008" />

===Synthesis===
A [[chemical synthesis]] of methyltestosterone from [[dehydroepiandrosterone]] (DHEA) with [[methandriol]] as an [[chemical intermediate|intermediate]] proceeds as follows:<ref name="Lednicer2009">{{cite book| vauthors = Lednicer D |title=Strategies for Organic Drug Synthesis and Design|url=https://books.google.com/books?id=fEwl6Qev-mUC&pg=PA144|date=4 March 2009|publisher=John Wiley & Sons|isbn=978-0-470-39959-0|pages=144–}}</ref><ref name="Algar2010">{{cite book| vauthors = Algar A |title=Textbook Of Medicinal Chemistry|url=https://books.google.com/books?id=WmrgauReT48C&pg=PA212|year=2010|publisher=Elsevier Health Sciences|isbn=978-81-312-2190-7|pages=212–}}</ref>

[[File:Methyltestosterone synthesis.png|class=skin-invert-image|700px|thumb|left]]{{Clear}}

==History==
Methyltestosterone was first [[chemical synthesis|synthesized]] in 1935 along with [[methandriol]] and [[mestanolone]].<ref name="pmid8674183">{{cite journal | vauthors = Schänzer W | title = Metabolism of anabolic androgenic steroids | journal = Clinical Chemistry | volume = 42 | issue = 7 | pages = 1001–1020 | date = July 1996 | pmid = 8674183 | doi = 10.1093/clinchem/42.7.1001 | doi-access = free }}</ref><ref name="RuzickaGoldberg1935">{{cite journal| vauthors = Ruzicka L, Goldberg MW, Rosenberg HR |title=Sexualhormone X. Herstellung des 17-Methyl-testosterons und anderer Androsten- und Androstanderivate. Zusammenhänge zwischen chemischer Konstitution und männlicher Hormonwirkung|journal=Helvetica Chimica Acta|volume=18|issue=1|year=1935|pages=1487–1498|issn=0018-019X|doi=10.1002/hlca.193501801203}}</ref><ref name="Hohl2017" /><ref name="ThiemeHemmersbach2009" /><ref name="pmid11589254">{{cite journal | vauthors = Shahidi NT | title = A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids | journal = Clinical Therapeutics | volume = 23 | issue = 9 | pages = 1355–1390 | date = September 2001 | pmid = 11589254 | doi = 10.1016/s0149-2918(01)80114-4 }}</ref> It was the second synthetic AAS to be developed, following [[mesterolone]] (1α-methyl-DHT) in 1934, and was the first 17α-alkylated AAS to be synthesized.<ref name="Hohl2017" /><ref name="ThiemeHemmersbach2009" /><ref name="pmid11589254" /> The drug was introduced for medical use in 1936.<ref name="NARD1956">{{cite book|title=N.A.R.D. journal|url=https://books.google.com/books?id=qO4jAQAAMAAJ|date=July 1956|publisher=National Association of Retail Druggists}}</ref><ref name="Llewellyn2009" />

==Society and culture==
[[Image:Methyltestosterone.jpg|200px|thumb|right|A confiscated capsule of illicit methyltestosterone.]]

===Generic names===
''Methyltestosterone'' is the {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}} of the drug and its [[generic term|generic name]] in [[English language|English]] and [[Japanese language|Japanese]], while ''méthyltestostérone'' is its {{abbrlink|DCF|Dénomination Commune Française}} and [[French language|French]] name and ''metiltestosterone'' is its {{abbrlink|DCIT|Denominazione Comune Italiana}} and [[Italian language|Italian]] name.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA179|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=179–}}</ref><ref name="Drugs.com">{{Cite web | url=https://www.drugs.com/international/methyltestosterone.html |title = Methyltestosterone}}</ref> The generic name of the drug is ''methyltestosterone'' in [[Latin language|Latin]], ''methyltestosteron'' in [[German language|German]], and ''metiltestosterona'' in [[Spanish language|Spanish]].<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" /> Methyltestosterone is also known by its former developmental code name ''NSC-9701''.<ref name="MortonHall2012" /><ref name="Drugs.com" />

===Brand names===
Brand names under which methyltestosterone is or has been marketed for medical use include Afro, Agovirin, Android, Androral, Mesteron, Metandren, Methitest, Methyltestosterone, Methyl Testosterone, Oraviron, Oreton, Oreton Methyl, Testormon, Testovis, Testred, and Virilon, among others.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="Drugs@FDA" />

====With an estrogen====
{{Main|Esterified estrogens/methyltestosterone}}

Methyltestosterone is available at a low-dose in combination with [[esterified estrogens]] for the treatment of menopausal symptoms like [[hot flash]]es in women under the brand names Covaryx, Essian, Estratest, Menogen, and Syntest.<ref name="Llewellyn2009" /><ref name="MayoClinic">{{Cite web | url=http://www.mayoclinic.org/drugs-supplements/esterified-estrogens-and-methyltestosterone-oral-route/description/drg-20073253 | title=Esterified Estrogens and Methyltestosterone (Oral Route) Description and Brand Names | website=[[Mayo Clinic]]}}</ref>

===Availability===
[[File:Methyltestosterone availability.png|thumb|right|300px|Availability of methyltestosterone in countries throughout the world. Blue is currently or formerly marketed.]]

====United States====
{{See also|List of androgens/anabolic steroids available in the United States}}

Although it is not commonly used, methyltestosterone is one of the few AAS that remains available for medical use in the [[United States]].<ref name="Llewellyn2009" /><ref name="Drugs@FDA">{{cite web | title = Drugs@FDA: FDA Approved Drug Products | publisher = United States Food and Drug Administration | access-date = 28 June 2017 | url = http://www.accessdata.fda.gov/scripts/cder/daf/}}</ref> The others are [[testosterone (medication)|testosterone]], [[testosterone cypionate]], [[testosterone enanthate]], [[testosterone undecanoate]], [[oxandrolone]], [[oxymetholone]], and [[fluoxymesterone]].<ref name="Drugs@FDA" />

====Other countries====
Methyltestosterone has also been marketed in many other countries throughout the world.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="Llewellyn2009" /><ref name="Muller1998">{{cite book|author=Muller|title=European Drug Index: European Drug Registrations, Fourth Edition|url=https://books.google.com/books?id=2HBPHmclMWIC&pg=PA36|date=19 June 1998|publisher=CRC Press|isbn=978-3-7692-2114-5|pages=36,400}}</ref><ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2109-IA157|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2109–}}</ref>

===Legal status===
Methyltestosterone, along with other AAS, is a [[Controlled Substances Act#Schedule III controlled substances|schedule III]] [[controlled substance]] in the [[United States]] under the [[Controlled Substances Act]] and a [[Controlled Drugs and Substances Act#Schedule IV|schedule IV]] controlled substance in [[Canada]] under the [[Controlled Drugs and Substances Act]].<ref name="FFFLM2006">{{cite book|author=Steven B. Karch |title=Drug Abuse Handbook | edition = Second |url=https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30|date=21 December 2006|publisher=CRC Press|isbn=978-1-4200-0346-8|pages=30–}}</ref><ref name="LilleySnyder2016">{{cite book| vauthors = Lilley LL, Snyder JS, Collins SR |title=Pharmacology for Canadian Health Care Practice|url=https://books.google.com/books?id=dNgoDwAAQBAJ&pg=PA50|date=5 August 2016|publisher=Elsevier Health Sciences|isbn=978-1-77172-066-3|pages=50–}}</ref>

==See also==
* [[Esterified estrogens/methyltestosterone]]
* [[Conjugated estrogens/methyltestosterone]]

==References==
{{Reflist}}

==Further reading==
{{refbegin}}
* {{cite journal | vauthors = Phillips EH, Ryan S, Ferrari R, Green C | title = Estratest and Estratest HS (esterified estrogens and methyltestosterone) therapy: a summary of safety surveillance data, January 1989 to August 2002 | journal = Clin Ther | volume = 25 | issue = 12 | pages = 3027–43 | year = 2003 | pmid = 14749144 | doi=10.1016/s0149-2918(03)90090-7}}
* {{cite journal | vauthors = Kabat GC, Kamensky V, Heo M, Bea JW, Hou L, Lane DS, Liu S, Qi L, Simon MS, Wactawski-Wende J, Rohan TE | title = Combined conjugated esterified estrogen plus methyltestosterone supplementation and risk of breast cancer in postmenopausal women | journal = Maturitas | volume = 79 | issue = 1 | pages = 70–6 | year = 2014 | pmid = 25011395 | doi = 10.1016/j.maturitas.2014.06.006}}
* {{cite journal | vauthors = ((El-Desoky el-SI)), Reyad M, Afsah EM, Dawidar AA | title = Synthesis and chemical reactions of the steroidal hormone 17α-methyltestosterone | journal = Steroids | volume = 105 | pages = 68–95 | year = 2016 | pmid = 26639430 | doi = 10.1016/j.steroids.2015.11.004| s2cid = 32620483 }}
{{refend}}

==External links==
* {{cite web | url = https://anabolic.org/methyltestosterone/ | title = Methyltestosterone | work = William Llewellyn's Anabolic.org | access-date = 2020-04-01 | archive-date = 2019-12-31 | archive-url = https://web.archive.org/web/20191231191029/https://anabolic.org/methyltestosterone/ | url-status = dead }}

{{Testosterone}}
{{Androgens and antiandrogens}}
{{Androgen receptor modulators}}
{{Estrogen receptor modulators}}

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