Androstanolone

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Androstanolone
Androstanolone.svg
Dihydrotestosterone-3D-balls.png
Clinical data
Trade names Anaboleen, Anabolex, Anaprotin, Andractim, Androlone, Apeton, Gelovit, Neodrol, Ophtovital, Pesomax, Stanaprol, and Stanolone
Pregnancy
category
  • X
Routes of
administration
Transdermal (gel), in the cheek, under the tongue, intramuscular injection (as esters)
ATC code
Pharmacokinetic data
Bioavailability Oral: Very low
Intramuscular: High
Metabolism Liver
Biological half-life 2.8 hours[1]
Excretion Urine
Identifiers
Synonyms Stanolone; Dihydrotestosterone; DHT; 5α-Dihydrotestosterone; 5α-DHT
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
Formula C19H30O2
Molar mass 290.442 g/mol
3D model (JSmol)
 NYesY (what is this?)  (verify)

Androstanolone, or stanolone, also known as dihydrotestosterone (DHT), is a naturally occurring anabolic-androgenic steroid (AAS) and androgen steroid hormone which is used medically in the treatment of male hypogonadism (androgen deficiency). It is a derivative of testosterone, specifically being 5α-dihydrotestosterone, and is a potent agonist of the androgen receptor (AR). Relative to testosterone, androstanolone is a considerably more potent as an AR agonist.

Medical uses[edit]

Androstanolone is available in pharmaceutical formulations for medical use as an androgen and AAS.[2] It is used mainly in the treatment of male hypogonadism.[3]

Side effects[edit]

Adverse effects of androstanolone are similar to those of other AAS and include androgenic side effects like oily skin, acne, seborrhea, increased facial/body hair growth, scalp hair loss, and increased aggressiveness and sex drive.[4][5] In women, androstanolone can cause partially irreversible virilization, for instance voice deepening, hirsutism, clitoromegaly, breast atrophy, and muscle hypertrophy, as well as menstrual disturbances and reversible infertility.[4][5] In men, the drug may also cause hypogonadism, testicular atrophy, and reversible infertility at sufficiently high dosages.[4][5]

Androstanolone can have adverse effects on the cardiovascular system, especially with long-term administration of high dosages.[4] AAS like androstanolone 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.[4] Unlike many other AAS, androstanolone is not aromatized and has no risk of estrogenic side effects like gynecomastia, fluid retention, or edema.[4][5] In addition, as it is not a 17α-alkylated AAS and is administered parenterally, androstanolone has no risk of hepatotoxicity.[4][5]

Pharmacology[edit]

Androstanolone is a potent agonist of the AR. It has an affinity (Kd) of 0.25 to 0.5 nM for the human AR, which is about 2- to 3-fold higher than that of testosterone (Kd = 0.4 to 1.0 nM)[6] and the dissociation rate of androstanolone from the AR is also about 5-fold slower than that of testosterone.[7] The EC50 of androstanolone for activation of the AR is 0.13 nM, which is about 5-fold stronger than that of testosterone (EC50 = 0.66 nM).[8] In bioassays, androstanolone has been found to be 2.5- to 10-fold more potent than testosterone.[6]

Unlike testosterone and various other AAS, androstanolone cannot be aromatized, and for this reason, poses no risk of estrogenic side effects like gynecomastia at any dosage.[9] In addition, androstanolone cannot be metabolized by 5α-reductase (as it is already 5α-reduced), and for this reason, is not potentiated in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland, thereby improving its ratio of anabolic to androgenic effects. However, androstanolone is nonetheless described as a very poor anabolic agent.[4] This is attributed to its high affinity as a substrate for 3α-hydroxysteroid dehydrogenase (3α-HSD), which is highly expressed in skeletal muscle and inactivates androstanolone into 3α-androstanediol, a metabolite with very weak AR activity.[4] Unlike androstanolone, testosterone is very resistant to metabolism by 3α-HSD, and so is not similarly inactivated in skeletal muscle.[4]

Pharmacokinetics[edit]

The terminal half-life of androstanolone in the circulation (53 minutes) is longer than that of testosterone (34 minutes), and this may account for some of the difference in their potency.[10] A study of transdermal androstanolone and testosterone treatment reported terminal half-lives of 2.83 hours and 1.29 hours, respectively.[1]

Chemistry[edit]

Androstanolone, also known as 5α-androstan-17β-ol-3-one or as 5α-dihydrotestosterone (5α-DHT), is a naturally occurring androstane steroid with a ketone group at the C3 position and a hydroxyl group at the C17β position.[11][12] It is the derivative of testosterone in which the double bond between the C4 and C5 positions has been reduced or hydrogenated.[11][12] Close synthetic relatives of androstanolone include the non-17α-alkylated dromostanolone (2α-methyl-DHT), mesterolone (1α-methyl-DHT), and metenolone (1-methyl-δ1-DHT) and the 17α-alkylated oxandrolone (2-oxa-17α-methyl-DHT), oxymetholone (2-hydroxymethylene-17α-methyl-DHT), and stanozolol (a 2,3-pyrazole A ring-fused derivative of 17α-methyl-DHT).[4][5]

Several C17β ester prodrugs of DHT, including androstanolone benzoate, androstanolone enanthate, androstanolone propionate, and androstanolone valerate, have been developed and introduced for medical use as AAS.[11][12][13] A few others, including dihydrotestosterone acetate, dihydrotestosterone butyrate, and dihydrotestosterone formate, have also been developed but were never marketed.[11]

History[edit]

Androstanolone was first discovered and synthesized in 1935 by Adolf Butenandt and his colleagues.[14][15] It was first introduced for medical use in 1953, under the brand name Neodrol in the United States,[16][17][18] and was subsequently marketed in the United Kingdom and other European countries.[16]

Society and culture[edit]

Generic names[edit]

When used as a drug, androstanolone is referred to as androstanolone (INN) or as stanolone (BAN) rather than as DHT.[2][11][12]

Brand names[edit]

Brand names of androstanolone include Anaboleen, Anabolex, Anaprotin (UK), Andractim (formerly AndroGel-DHT) (FR, BE, LU), Androlone, Apeton, Gelovit (ES), Neodrol, Ophtovital, (DE), Pesomax (IT), Stanaprol, and Stanolone, among others.[2][11][12][3][19]

Availability[edit]

The availability of pharmaceutical androstanolone is limited; it is not available in the United States or Canada,[20][21] but is available in certain European countries, including the United Kingdom, Germany, France, Spain, Italy, Belgium, and Luxembourg.[12][3]

The available formulations of androstanolone include buccal or sublingual tablets (Anabolex, Stanolone), topical gels (Andractim, Gelovit, Ophtovital), and, as esters in oil, injectables like androstanolone propionate (Pesomax) and androstanolone valerate (Apeton).[2][3][19] Androstanolone benzoate (Ermalone-Amp, Hermalone, Sarcosan) and androstanolone enanthate (Anaboleen Depot) are additional androstanolone esters that are also available for medical use in some countries.[11] Androstanolone esters act as prodrugs of androstanolone in the body and have a long-lasting depot when given via intramuscular injection.[2]

Research[edit]

Cachexia[edit]

Androstanolone was under development in a topical formulation for the treatment of cachexia in cancer patients, and reached phase III clinical trials for this indication, but ultimately was not introduced for this purpose.[3] Although androstanolone itself has not been approved for the treatment of cachexia, an orally active synthetic derivative of androstanolone, oxandrolone (2-oxa-17α-methylandrostanolone), is approved and used for this indication.[22][23]

References[edit]

  1. ^ a b von Deutsch DA, Abukhalaf IK, Lapu-Bula R (15 October 2003). "Anabolic Doping Agents". In Mozayani A, Raymon L. Handbook of Drug Interactions: A Clinical and Forensic Guide. Springer Science & Business Media. pp. 510–. ISBN 978-1-59259-654-6. doi:10.1007/978-1-61779-222-9_15. 
  2. ^ a b c d e Hyde TE, Gengenbach MS (2007). Conservative Management of Sports Injuries. Jones & Bartlett Learning. pp. 1100–. ISBN 978-0-7637-3252-3. 
  3. ^ a b c d e "Androstanolone Drug Profile". Adis Insight. 4 December 2006. 
  4. ^ a b c d e f g h i j k William Llewellyn (2009). Anabolics. Molecular Nutrition Llc. pp. 19,163. ISBN 978-0967930473. 
  5. ^ a b c d e f Kicman, A T (2008). "Pharmacology of anabolic steroids". British Journal of Pharmacology. 154 (3): 502–521. PMC 2439524Freely accessible. PMID 18500378. doi:10.1038/bjp.2008.165. 
  6. ^ a b Mozayani A, Raymon L (18 September 2011). Handbook of Drug Interactions: A Clinical and Forensic Guide. Springer Science & Business Media. pp. 656–. ISBN 978-1-61779-222-9. 
  7. ^ Grino PB, Griffin JE, Wilson JD (February 1990). "Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone". Endocrinology. 126 (2): 1165–72. PMID 2298157. doi:10.1210/endo-126-2-1165. 
  8. ^ Wilderer PA (1 September 2010). "Bioassays for Estrogenic and Androgenic Effects of Water Constituents". Treatise on Water Science, Four-Volume Set. Newnes. pp. 1805–. ISBN 978-0-444-53199-5. 
  9. ^ Malven PV (12 January 1993). Mammalian Neuroendocrinology. CRC Press. pp. 228–. ISBN 978-0-8493-8757-9. 
  10. ^ Diamanti-Kandarakis E (1999). "Current aspects of antiandrogen therapy in women". Current Pharmaceutical Design. 5 (9): 707–23. PMID 10495361. 
  11. ^ a b c d e f g Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 640–. ISBN 978-1-4757-2085-3. 
  12. ^ a b c d e f Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 63–. ISBN 978-3-88763-075-1. 
  13. ^ Morton I, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 261–. ISBN 978-94-011-4439-1. 
  14. ^ R Schnitzer (1 January 1967). Experimental Chemotherapy. Elsevier Science. pp. 156–. ISBN 978-0-323-14611-1. 
  15. ^ H.-L. Krüskemper (22 October 2013). Anabolic Steroids. Elsevier. pp. 12–. ISBN 978-1-4832-6504-9. 
  16. ^ a b William Andrew Publishing (2007). Pharmaceutical Manufacturing Encyclopedia. William Andrew Pub. ISBN 978-0-8155-1526-5. 
  17. ^ Newsweek. Newsweek. 1953. 
  18. ^ New and Nonofficial Drugs. Lippincott. 1958. 
  19. ^ a b List PH, Hörhammer L (12 March 2013). Chemikalien und Drogen: Teil B: R, S. Springer-Verlag. pp. 523–. ISBN 978-3-642-66377-2. 
  20. ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 16 November 2016. 
  21. ^ "Drug Product Database - Health Canada". Health Canada. Retrieved 13 November 2016. 
  22. ^ Nelms M, Sucher KP, Lacey K, Roth SL (16 June 2010). Nutrition Therapy and Pathophysiology. Cengage Learning. pp. 766–. ISBN 1-133-00809-7. 
  23. ^ Mantovani G (6 October 2007). Cachexia and Wasting: A Modern Approach. Springer Science & Business Media. pp. 673–. ISBN 978-88-470-0552-5.