Methyltestosterone

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Methyltestosterone
Methyltestosterone.svg
Methyltestosterone-3D-ball-and-stick.png
Clinical data
Trade names Agoviron, Android, Metandren, Oraviron, Oreton, Testovis, Testred, Virilon, others
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
Routes of
administration		 Oral, buccal, sublingual[1][2]
Drug class Androgen; Anabolic-androgenic steroid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~70%[3]
Protein binding 98%[4]
Metabolism Liver
Biological half-life ~3 hours[3]
Duration of action 1–3 days[4]
Excretion Urine: 90%[4]
Feces: 6%[4][5]
Identifiers
Synonyms NSC-9701; 17α-Methyltestosterone; 17α-Methylandrost-4-en-17β-ol-3-one[6][7][8]
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.000.333
Chemical and physical data
Formula C20H30O2
Molar mass 302.451 g/mol
3D model (JSmol)
 NYesY (what is this?)  (verify)

Methyltestosterone (brand names Agovirin, Android, Metandren, Oreton, Testred, Virilon, others) is a synthetic, orally active anabolic-androgenic steroid (AAS) which is used in the treatment of androgen deficiency in males and for a number of other indications.[6][7][8][1] It is also used illicitly for physique- or performance-enhancing purposes by athletes and bodybuilders.[1] The drug was synthesized in 1935 shortly following the discovery of testosterone, and was one of the first synthetic AAS to be developed.[1][9][10] Although it is not as commonly used as other AAS for various reasons, methyltestosterone continues to be used medically even today.[1][11]

Medical uses[edit]

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.[1][2][12]

Non-medical uses[edit]

Methyltestosterone is used for physique- or performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters, although it is not commonly used relative to other AAS for such purposes.[1]

Dosage[edit]

The dosages of methyltestosterone used are 10 to 50 mg/day in men for common medical uses and physique- and performance-enhancing purposes and 2.5 mg/day in women for menopausal symptoms.[1] Higher dosages of as much as 200 mg/day have been used to treat women with inoperable breast cancer that has failed to respond to other therapies.[1]

Contraindications[edit]

Methyltestosterone should be used with caution in women and children, as it can cause irreversible virilization.[1] Due to its estrogenicity, methyltestosterone can also accelerate epiphyseal closure and thereby produce short stature in children and adolescents.[1] It can worsen symptoms in men with benign prostatic hyperplasia.[1] Methyltestosterone should not be used in men with prostate cancer, as androgens can accelerate tumor progression.[1] The drug should be used with caution in patients with pre-existing hepatotoxicity, due to its own potential for hepatotoxicity.[1]

Side effects[edit]

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 gynecomastia, fluid retention, and edema.[1][13] 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.[1][13] In men, the drug may also cause hypogonadism, testicular atrophy, and reversible infertility at sufficiently high dosages.[1][13]

Methyltestosterone can sometimes cause hepatotoxicity, for instance elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma, with extended use.[1][13][14] It can also have adverse effects on the cardiovascular system.[1] 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.[1] With long-term treatment, AAS can increase the risk of benign prostatic hyperplasia and prostate cancer.[1] Violent and even homicidal behavior, hypomania/mania, depression, suicidality, delusions, and psychosis have all been associated with very high dosages of AAS.[15]

Interactions[edit]

Aromatase inhibitors can be used to reduce or prevent the estrogenic effects of methyltestosterone and 5α-reductase inhibitors can be used to prevent its potentiation in so-called "androgenic" tissues and thereby improve its ratio of anabolic to androgenic activity and reduce its rate of androgenic side effects.[1] Antiandrogens like bicalutamide and cyproterone acetate can block both the anabolic and androgenic effects of AAS like methyltestosterone.

Pharmacology[edit]

As an AAS, methyltestosterone is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT).[1][13] 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).[1][13] 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.[1][13] Due to efficient aromatization into the potent and metabolically resistant estrogen methylestradiol (17α-methylestradiol), methyltestosterone has relatively high estrogenicity and hence potential for estrogenic side effects such as gynecomastia and fluid retention.[10][16] The drug possesses negligible progestogenic activity.[1][13]

Due to its combined disadvantages of a relatively poor ratio of anabolic to androgenic activity, unusually high estrogenicity, and the potential for hepatotoxicity, methyltestosterone has not been used as commonly as many other AAS either in medicine or for physique- or performance-enhancing purposes.[1]

Pharmacokinetics[edit]

Because of its C17α methyl group, methyltestosterone has dramatically improved oral bioavailability and metabolic stability relative to testosterone, and for this reason, unlike testosterone, is orally active.[1][13] The oral bioavailability of methyltestosterone is about 70%, and its terminal half-life is approximately 3 hours (range 2.5–3.5 hours),[3][5] with a duration of action of 1 to 3 days.[4] Its duration is described as relatively short among AAS.[17] Methyltestosterone can also be taken buccally or sublingually, and this is said to approximately double its bioavailability.[1] The drug is highly protein-bound, by approximately 98%, including to sex hormone-binding globulin (SHBG) with about 25% of the affinity of testosterone.[4][1] It is excreted 90% in the urine as conjugates and metabolites, and 6% in feces.[4]

Chemistry[edit]

See also: List of androgens/anabolic steroids

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.[6][7][1] Close synthetic relatives of methyltestosterone include metandienone (17α-methyl-δ1-testosterone) and fluoxymesterone (9α-fluoro-11β-hydroxy-17α-methyltestosterone).[1][13]

Derivatives[edit]

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.[1][13]

Synthesis[edit]

A chemical synthesis of methyltestosterone from dehydroepiandrosterone (DHEA) proceeds as follows:[18][19]

Methyltestosterone synthesis.png

History[edit]

Methyltestosterone was first synthesized in 1935.[9][10][20] 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 developed.[9][10][20] The drug was introduced for medical use in 1936.[21][1]

Society and culture[edit]

A confiscated capsule of illicit methyltestosterone.

Generic name[edit]

Methyltestosterone is the INN, USAN, USP, BAN, and JAN of the drug and its generic name in English and Japanese, while méthyltestostérone is its DCF and French name and metiltestosterone is its DCIT and Italian name.[6][7][8] The generic name of the drug is methyltestosterone in Latin, methyltestosteron in German, and metiltestosterona in Spanish.[6][7][8] Methyltestosterone is also known by its former developmental code name NSC-9701.[8]

Brand names[edit]

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.[6][7][8][11]

With an estrogen[edit]

Main article: 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.[1][22]

Availability[edit]

United States[edit]

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.[1][11] The others are testosterone (and esters), nandrolone decanoate, oxandrolone, oxymetholone, and fluoxymesterone.[11]

Other countries[edit]

Methyltestosterone is also marketed in many other countries throughout the world.[6][7][8]

Legal status[edit]

Methyltestosterone, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act and an schedule IV controlled substance in Canada under the Controlled Drugs and Substances Act.[23][24]

References[edit]

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj William Llewellyn (2009). Anabolics. Molecular Nutrition Llc. pp. 16,19,22,27,30,36,39,42,46,291–293. ISBN 978-0967930473. 
  2. ^ a b Manuchair Ebadi (31 October 2007). Desk Reference of Clinical Pharmacology, Second Edition. CRC Press. pp. 434–. ISBN 978-1-4200-4744-8. 
  3. ^ a b c Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1360–. ISBN 978-1-60913-345-0. 
  4. ^ a b c d e f g Teri Moser Woo; Marylou V Robinson (3 August 2015). Pharmacotherapeutics For Advanced Practice Nurse Prescribers. F.A. Davis. pp. 618–. ISBN 978-0-8036-4581-3. 
  5. ^ a b Kourosh Saeb-Parsy (18 June 1999). Instant Pharmacology. John Wiley & Sons. pp. 260–. ISBN 978-0-471-97639-4. 
  6. ^ a b c d e f g J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 653–. ISBN 978-1-4757-2085-3. 
  7. ^ a b c d e f g Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 676–. ISBN 978-3-88763-075-1. 
  8. ^ a b c d e f g https://www.drugs.com/international/methyltestosterone.html
  9. ^ a b c Alexandre Hohl (6 April 2017). Testosterone: From Basic to Clinical Aspects. Springer. pp. 204–. ISBN 978-3-319-46086-4. 
  10. ^ a b c d Detlef Thieme; Peter Hemmersbach (18 December 2009). Doping in Sports. Springer Science & Business Media. pp. 101,470. ISBN 978-3-540-79088-4. 
  11. ^ a b c d "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 28 June 2017. 
  12. ^ John A. Yagiela; Frank J. Dowd; Bart Johnson; Angelo Mariotti, Enid A. Neidle (19 March 2010). Pharmacology and Therapeutics for Dentistry - E-Book. Elsevier Health Sciences. pp. 569–. ISBN 0-323-07824-9. 
  13. ^ a b c d e f g h i j k Kicman, A T (2008). "Pharmacology of anabolic steroids". British Journal of Pharmacology. 154 (3): 502–521. PMC 2439524 Freely accessible. PMID 18500378. doi:10.1038/bjp.2008.165. 
  14. ^ Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 141–. ISBN 978-0-08-093292-7. 
  15. ^ Benjamin J. Sadock; Virginia A. Sadock (26 December 2011). Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Lippincott Williams & Wilkins. ISBN 978-1-4511-7861-6. 
  16. ^ Andrea R. Genazzani (17 January 2006). Postmenopausal Osteoporosis: Hormones & Other Therapies. Taylor & Francis US. pp. 243–. ISBN 978-1-84214-311-7. 
  17. ^ Lynn Crespo; Lynn Wecker; George Dunaway; Carl Faingold, Stephanie Watts (1 April 2009). Brody's Human Pharmacology - E-Book. Elsevier Health Sciences. pp. 469–. ISBN 0-323-07575-4. 
  18. ^ Daniel Lednicer (4 March 2009). Strategies for Organic Drug Synthesis and Design. John Wiley & Sons. pp. 144–. ISBN 978-0-470-39959-0. 
  19. ^ Algar (2010). Textbook Of Medicinal Chemistry. Elsevier Health Sciences. pp. 212–. ISBN 81-312-2190-3. 
  20. ^ a b Shahidi NT (2001). "A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids". Clin Ther. 23 (9): 1355–90. PMID 11589254. doi:10.1016/s0149-2918(01)80114-4. 
  21. ^ N.A.R.D. journal. National Association of Retail Druggists. July 1956. 
  22. ^ http://www.mayoclinic.org/drugs-supplements/esterified-estrogens-and-methyltestosterone-oral-route/description/drg-20073253
  23. ^ Steven B. Karch, MD, FFFLM (21 December 2006). Drug Abuse Handbook, Second Edition. CRC Press. pp. 30–. ISBN 978-1-4200-0346-8. 
  24. ^ Linda Lane Lilley; Julie S. Snyder; Shelly Rainforth Collins (5 August 2016). Pharmacology for Canadian Health Care Practice. Elsevier Health Sciences. pp. 50–. ISBN 978-1-77172-066-3. 
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