methyltestosterone

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 menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and energy), postpartum breast pain and engorgement, and breast cancer in women. 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.{{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 }} It was also approved in low doses in combination with esterified estrogens for the treatment of moderate to severe vasomotor symptoms associated with menopause in women in the United States, but this formulation was discontinued and hence is no longer used.{{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 }}

Methyltestosterone is less effective in inducing masculinization than testosterone, but is useful for maintaining established masculinization in adults.{{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–}}

The dosages of methyltestosterone used are 10 to 50 mg/day in men for common medical uses like hypogonadism and delayed puberty as well as physique- and performance-enhancing purposes and 2.5 mg/day in women for menopausal symptoms. Higher dosages of 50 to 200 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.

{{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}}

Methyltestosterone is used for physique- and performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters, although it is not commonly used relative to other AAS for such purposes.

{{See also|Esterified estrogens/methyltestosterone|Conjugated estrogens/methyltestosterone}}

Methyltestosterone is typically used as an oral medication. It is also available under the brand names Metandren and Oreton Methyl for use specifically by buccal or sublingual administration.{{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}} Methyltestosterone is available in the form of 2, 5, 10, and 25 mg oral tablets.{{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–}}{{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–}} It was also available in combination with estrogens as esterified estrogens/methyltestosterone (0.625 mg/1.25 mg, 1.25 mg/2.5 mg) and conjugated estrogens/methyltestosterone (0.625 mg/5.0 mg, 1.25 mg/10 mg).

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

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

Adverse effects of methyltestosterone include androgenic side effects like oily skin, acne, seborrhea, increased facial/body hair growth, scalp hair loss, increased aggressiveness and sex drive, and spontaneous erections, as well as estrogenic side effects like breast tenderness, gynecomastia, fluid retention, and edema. In women, methyltestosterone can cause partially irreversible virilization, for instance voice deepening, hirsutism, clitoromegaly, breast atrophy, and muscle hypertrophy, as well as menstrual disturbances and reversible infertility. In men, the drug may also cause hypogonadism, testicular atrophy, and reversible infertility at sufficiently high dosages.

Methyltestosterone can sometimes cause hepatotoxicity, for instance elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma, with extended use.{{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–}} It can also have adverse effects on the cardiovascular system. 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 thrombic events such as embolism and stroke. With long-term treatment, AAS can increase the risk of benign prostatic hyperplasia and prostate cancer. Violent and even homicidal behavior, hypomania/mania, depression, suicidality, delusions, and psychosis have all been associated with very high dosages of AAS.{{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}}

Aromatase inhibitors can be used to reduce or prevent the estrogenic effects of methyltestosterone and 5α-reductase inhibitors can be used to reduce its virilizing effects and thereby improve its ratio of anabolic to androgenic activity and reduce its rate of androgenic side effects.

{{Relative androgenic to anabolic activity in animals}}

As an AAS, methyltestosterone is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT).{{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 }} It is a substrate for 5α-reductase like testosterone, and so is potentiated analogously in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland via transformation into the more potent AR agonist mestanolone (17α-methyl-DHT). As such, methyltestosterone has a relatively low ratio of anabolic to androgenic activity, with a similar ratio to that of testosterone (close to 1:1), and this makes it among the most androgenic AAS. Due to efficient aromatization into the potent and metabolism-resistant estrogen methylestradiol (17α-methylestradiol), methyltestosterone has relatively high estrogenicity and hence potential for estrogenic side effects such as gynecomastia and fluid retention.{{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–}} The drug possesses negligible progestogenic activity.

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.

Methyltestosterone has dramatically improved oral bioavailability and metabolic stability relative to testosterone. This difference is due to the C17α methyl group, which results in steric hindrance and prevents metabolism. The oral bioavailability of methyltestosterone is about 70%, and it is well-absorbed from the gastrointestinal tract.{{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–}} Methyltestosterone can also be taken buccally or sublingually. 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.

Circulating levels of methyltestosterone with administration of 1.25 to 2.5 mg/day oral methyltestosterone in women are in the range of 20 to 30 ng/dL.{{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 }} For comparison to testosterone, methyltestosterone is at least as potent as an AAS. 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.

Methyltestosterone is highly protein-bound, by approximately 98%. The medication has low but significant affinity for human serum sex hormone-binding globulin (SHBG), about 25% of that of testosterone and 5% of that of DHT.{{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 }}

The biological half-life of methyltestosterone is approximately 3 hours (range 2.5–3.5 hours).{{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–}} The duration of action of methyltestosterone is said to be 1 to 3 days, and is described as relatively short among AAS.{{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–}}{{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–}}

Methyltestosterone is excreted 90% in the urine as conjugates and other metabolites, and 6% in feces.

{{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, 17α-alkylated androstane steroid and a derivative of testosterone differing from it only in the presence of a methyl group at the C17α position.{{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–}}{{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–}} Close synthetic relatives of methyltestosterone include metandienone (17α-methyl-δ¹-testosterone) and fluoxymesterone (9α-fluoro-11β-hydroxy-17α-methyltestosterone).

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

Methyltestosterone and ethyltestosterone (17α-ethyltestosterone) are the parent structures 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.

A chemical synthesis of methyltestosterone from dehydroepiandrosterone (DHEA) with methandriol as an intermediate proceeds as follows:{{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–}}{{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–}}

File:Methyltestosterone synthesis.png{{Clear}}

Methyltestosterone was first synthesized in 1935 along with methandriol and mestanolone.{{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 }}{{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}}{{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 }} 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. The drug was introduced for medical use in 1936.{{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}}

Image:Methyltestosterone.jpg

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 name in English and Japanese, while méthyltestostérone is its {{abbrlink|DCF|Dénomination Commune Française}} and French name and metiltestosterone is its {{abbrlink|DCIT|Denominazione Comune Italiana}} and Italian name.{{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–}}{{Cite web | url=https://www.drugs.com/international/methyltestosterone.html |title = Methyltestosterone}} The generic name of the drug is methyltestosterone in Latin, methyltestosteron in German, and metiltestosterona in Spanish. Methyltestosterone is also known by its former developmental code name NSC-9701.

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.

{{Main|Esterified estrogens/methyltestosterone}}

Methyltestosterone is available at a low-dose in combination with esterified estrogens for the treatment of menopausal symptoms like hot flashes in women under the brand names Covaryx, Essian, Estratest, Menogen, and Syntest.{{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}}

File:Methyltestosterone availability.png

{{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.{{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/}} The others are testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, oxandrolone, oxymetholone, and fluoxymesterone.

Methyltestosterone has also been marketed in many other countries throughout the world.{{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}}{{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–}}

Methyltestosterone, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act and a schedule IV controlled substance in Canada under the Controlled Drugs and Substances Act.{{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–}}{{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–}}

• Esterified estrogens/methyltestosterone
• Conjugated estrogens/methyltestosterone

{{Reflist}}

{{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}}

• {{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}}

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