Testosterone undecanoate

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Testosterone undecanoate
Testosterone undecanoate.svg
Testosterone undecanoate molecule ball.png
Clinical data
Pronunciation /tɛˈstɒstərn ənˈdɛkənt/ teh-STOS-tə-rohn ən-DEK-ə-noh-ayt
Trade names Nebido, Aveed, Andriol, others
Synonyms TU; Testosterone undecylate; Testosterone 17β-undecanoate; ORG-538; CLR-610
Pregnancy
category
  • US: X (Contraindicated)
Routes of
administration
By mouth, intramuscular injection
Drug class Androgen; Anabolic steroid; Androgen ester
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Oral: 3–7%[citation needed]
Intramuscular: high
Protein binding High (testosterone)
Metabolism Liver
Metabolites Testosterone, undecanoic acid, metabolites of testosterone
Elimination half-life In TSO: 20.9 days (i.m.)[1][2]
In CO: 33.9 days (i.m.)[1][2]
Excretion Urine
Identifiers
CAS Number
  • 5949-44-0 ☑Y
PubChem CID
  • 65157
DrugBank
  • DB13946 ☑Y
ChemSpider
  • 58664 ☑Y
UNII
  • H16A5VCT9C
KEGG
  • D06087 ☑Y
ChEBI
  • CHEBI:135741 ☑Y
ChEMBL
  • ChEMBL2107067 ☑Y
ECHA InfoCard 100.025.193
Chemical and physical data
Formula C30H48O3
Molar mass 456.711 g/mol g·mol−1
3D model (JSmol)
  • Interactive image
  (verify)

Testosterone undecanoate, sold under the brand names Nebido, Aveed, and Andriol among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men.[3][1][4][5] It is also used in hormone therapy for transgender men.[6][7][8] It is taken by mouth two to three times per day with food or given by injection into muscle once every 12 weeks or so.[5][9]

Side effects of testosterone undecanoate include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.[5] The drug is a prodrug of testosterone, the biological ligand of the androgen receptor (AR) and hence is an androgen and anabolic steroid.[10][5] It has strong androgenic effects and moderate anabolic effects, which make it useful for producing masculinization and suitable for androgen replacement therapy.[5] Testosterone undecanoate is a testosterone ester and a prodrug of testosterone in the body.[4][3][1] Because of this, it is considered to be a natural and bioidentical form of testosterone.[11]

Testosterone undecanoate was introduced in China for use by injection and in Europe for use by mouth in the 1970s.[12][13] It became available for use by injection in Europe in the early to mid 2000s and in the United States in 2014.[14][15] A formulation for use by mouth is not currently available in the United States but is pending approval as of 2018.[16] Along with testosterone enanthate, testosterone cypionate, and testosterone propionate, testosterone undecanoate is one of the most widely used testosterone esters.[10][1][5] However, it has advantages over other testosterone esters in that it can be taken by mouth and in that it has a far longer duration when given by injection.[17][3][1][2][5] In addition to its medical use, testosterone undecanoate is used to improve physique and performance.[5] The drug is a controlled substance in many countries and so non-medical use is generally illicit.[5]

Medical uses

Testosterone undecanoate is used in androgen replacement therapy. It is specifically approved only for the treatment of hypogonadism.[18][19][20] As an intramuscular injection, it is administered at a dosage of 1,000 mg once every 12 weeks.[9] Conversely, oral testosterone undecanoate must be taken two or three times a day with food.[9][21]

Androgen replacement therapy formulations and dosages used in women

Route Medication Form(s) Major brand name(s) Dose range Frequency
Oral Testosterone undecanoatea Capsule Andriol 40–80 mg Every 1–2 days
Methyltestosteroneb Tablet Metandren; Estratest 0.5–10 mg Daily
Normethandronea,b Tablet Ginecoside 5 mg Daily
Tibolonea Tablet Livial 1.25–2.5 mg Daily
Prasterone (dehydroepiandrosterone)c Tablet N/A 25–100 mg Daily
Sublingual Testosteroned Tablet N/A 0.25–0.5 mg Daily
Methyltestosterone Tablet Metandren 0.25 mg Daily
Transdermal Testosteronea Patch Intrinsa 150–300 μg/day Every 3–4 days
Testosterone Cream; Gel AndroGel 5–10 mg Daily
Vaginal Testosteroned Cream; Gel N/A Unspecified Every 1–3 days
Prasterone (dehydroepiandrosterone) Insert Intrarosa 6.5 mg Daily
Intramuscular Testosterone enanthateb Oil Delatestryl; Ditate-DS 25–100 mg Every 4–6 weeks
Testosterone cypionateb Oil Depo-Testosterone; Depo-Testadiol 25–100 mg Every 4–6 weeks
Testosterone enanthate benzilic acid hydrazoneb,e Oil Climacteron 150 mg Every 4–8 weeks
Nandrolone decanoate Oil Deca-Durabolin 25–50 mg Every 6–12 weeks
Prasterone enanthatea,b Oil Gynodian Depot 200 mg Every 4–6 weeks
Subcutaneous Testosterone Implant Testopel 50–100 mg Every 3–6 months
Footnotes: a = Not available or no longer available in the United States. b = Alone and/or in combination with an estrogen. c = Over-the-counter. d = Compounded only. e = Discontinued. Sources: See template.

Side effects

Side effects of testosterone undecanoate include virilization among others.[5]

Anaphylaxis

The Reandron 1000 formulation (Nebido in the United States) contains 1,000 mg of testosterone undecanoate suspended in castor oil with benzyl benzoate for solubilization and as a preservative, and is administered by intramuscular injection. As an excipient, benzyl benzoate has been reported as a cause of anaphylaxis in a case in Australia.[22] Bayer includes this report in information for health professionals and recommends that physicians "should be aware of the potential for serious allergic reactions" to preparations of this type.[23] In Australia, reports to ADRAC, which evaluates reports of adverse drug reactions for the Therapeutic Goods Administration, show several reports of allergic issues since the anaphylaxis case from 2011.[citation needed]

Pharmacology

Pharmacodynamics

Relative androgenic to anabolic
activity in animals

Medication Ratio
Testosterone 1:1
Testosterone cypionate 1:1
Testosterone enanthate 1:1
Methyltestosterone 1:1
Fluoxymesterone 1:2
Oxymetholone 1:3
Oxandrolone 1:3–1:13
Nandrolone decanoate 1:2.5–1:4
Sources: See template.

Testosterone undecanoate is a prodrug of testosterone and is an androgen and anabolic–androgenic steroid (AAS). That is, it is an agonist of the androgen receptor (AR).

Pharmacokinetics

Testosterone undecanoate has a very long elimination half-life and mean residence time when given as a depot intramuscular injection.[24][1][2] Its elimination half-life is 20.9 days and its mean residence time is 34.9 days in tea seed oil, while its elimination half-life is 33.9 days and its mean residence time is 36.0 days in castor oil.[1][2] These values are substantially longer than those of testosterone enanthate (which, in castor oil, has values of 4.5 days and 8.5 days, respectively).[24] Testosterone undecanoate is administered via intramuscular injection once every three months or so.[9][25]

Pharmacokinetics of testosterone esters

Testosterone ester Form Route of administration Elimination half-life Mean residence time
Testosterone undecanoate Oil-filled capsules Oral 1.6 hours 3.7 hours
Testosterone propionate Oil solution Intramuscular injection 0.8 days 1.5 days
Testosterone enanthate Castor oil solution Intramuscular injection 4.5 days 8.5 days
Testosterone undecanoate Tea seed oil solution Intramuscular injection 20.9 days 34.9 days
Testosterone undecanoate Castor oil solution Intramuscular injection 33.9 days 36.0 days
Testosterone buciclatea Aqueous suspension Intramuscular injection 29.5 days 60.0 days
Notes: Testosterone cypionate has very similar pharmacokinetics to TE. Footnotes: a = Never marketed. Sources: See template.

Chemistry

Testosterone undecanoate, or testosterone 17β-undecanoate, is a synthetic androstane steroid and a derivative of testosterone.[26][27] It is an androgen ester; specifically, it is the C17β undecylate (undecanoate) ester of testosterone.[26][27] A related testosterone ester with a similarly very long duration is testosterone buciclate.[3][4]

Structural properties of major testosterone esters

Androgen Structure Ester Rel. MWb Rel. Tc Durationd
Position Moiety Type Lengtha Rank Group
Testosterone
Testosteron.svg
1.00 1.00 6 Short
Testosterone propionate
Testosterone propionate.svg
C17β Propanoic acid Straight-chain fatty acid 3 1.19 0.84 5 Short
Testosterone cypionate
Testosterone cypionate.svg
C17β Cyclopentylpropanoic acid Aromatic fatty acid – (~6) 1.43 0.70 4 Moderate
Testosterone enanthate
Testosterone enanthate.svg
C17β Heptanoic acid Straight-chain fatty acid 7 1.39 0.72 3 Moderate
Testosterone undecanoate
Testosterone undecanoate.svg
C17β Undecanoic acid Straight-chain fatty acid 11 1.58 0.63 2 Long
Testosterone buciclatee
Testosteronebuciclate structure.png
C17β Bucyclic acidf Aromatic carboxylic acid – (~9) 1.58 0.63 1 Long
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative molecular weight. c = Relative testosterone content by weight (i.e., relative androgenic potency). d = Duration by intramuscular or subcutaneous injection. e = Never marketed. f = Bucyclic acid = trans-4-Butylcyclohexane-1-carboxylic acid. Sources: See individual articles.

History

In the late 1970s, testosterone undecanoate was introduced for oral use in Europe,[12] although intramuscular testosterone undecanoate had already been in use in China for several years.[13] Intramuscular testosterone undecanoate was not introduced in Europe and the United States until much later, in the early to mid 2000s and 2014, respectively.[14][15] Testosterone undecanoate was approved in the United States after three previous rejections due to safety concerns.[28]

Society and culture

Generic names

Testosterone undecanoate is the generic name of the drug and its USAN and BAN.[26][27][29][30] It is also referred to as testosterone undecylate.[26][27][29][30]

Brand names

Testosterone undecanoate is or has been marketed under a variety of brand names including Aveed, Andriol, Androxon, Cernos Depot, Nebido, Panteston, Restandol, Nebido-R, Reandron 1000, and Undestor.[26][27][29][30]

Availability

Intramuscular testosterone undecanoate is available in the United States, Canada, Europe, and elsewhere in the world.[5][31][32] It is approved in over 100 countries worldwide.[31][5] Oral testosterone undecanoate is available in Canada, Europe, Mexico, Asia, and elsewhere but not in the United States.[31][33] Intramuscular testosterone undecanoate is marketed most commonly as Nebido in Canada and Europe and as Aveed in the United States while oral testosterone undecanoate is marketed most commonly as Andriol.[5][31][32]

Legal status

Testosterone undecanoate, 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.[34][35]

Research

As of June 2017, an oral formulation of testosterone undecanoate is in preregistration for the treatment of hypogonadism in the United States.[16]

As of January 2017, intramuscular testosterone undecanoate is in phase II clinical trials for the treatment of non-alcoholic steatohepatitis in the United Kingdom.[18]

References

  1. ^ a b c d e f g h Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (13 January 2010). Andrology: Male Reproductive Health and Dysfunction. Springer Science & Business Media. pp. 441–446. ISBN 978-3-540-78355-8.
  2. ^ a b c d e Behre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E (1999). "Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies". Eur. J. Endocrinol. 140 (5): 414–9. CiteSeerX 10.1.1.503.1752. doi:10.1530/eje.0.1400414. PMID 10229906.
  3. ^ a b c d Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (26 July 2012). Testosterone: Action, Deficiency, Substitution. Cambridge University Press. pp. 313–315, 321–322. ISBN 978-1-107-01290-5.
  4. ^ a b c Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1185–. ISBN 978-0-7817-1750-2.
  5. ^ a b c d e f g h i j k l m William Llewellyn (2011). Anabolics. Molecular Nutrition Llc. pp. 180–182, 331–334. ISBN 978-0-9828280-1-4.
  6. ^ Irwig MS (2017). "Testosterone therapy for transgender men". Lancet Diabetes Endocrinol. 5 (4): 301–311. doi:10.1016/S2213-8587(16)00036-X. PMID 27084565.
  7. ^ JW Jacobeit; LJ Gooren; HM Schulte (2007). "Long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals". The Journal of Sexual Medicine. 4 (5): 1479–84. doi:10.1111/j.1743-6109.2007.00556.x. PMID 17635694.
  8. ^ JW Jacobeit; LJ Gooren; HM Schulte (2009). "Safety aspects of 36 months of administration of long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals". European Journal of Endocrinology. 161 (5): 795–8. doi:10.1530/EJE-09-0412. PMID 19749027.
  9. ^ a b c d S. Bertelloni; O. Hiort (28 September 2010). New Concepts for Human Disorders of Sexual Development. S. Karger AG. pp. 256–. ISBN 978-3-8055-9569-8.
  10. ^ a b Kicman AT (2008). "Pharmacology of anabolic steroids". Br. J. Pharmacol. 154 (3): 502–21. doi:10.1038/bjp.2008.165. PMC 2439524. PMID 18500378.
  11. ^ Santoro N, Braunstein GD, Butts CL, Martin KA, McDermott M, Pinkerton JV (2016). "Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement". J. Clin. Endocrinol. Metab. 101 (4): 1318–43. doi:10.1210/jc.2016-1271. PMID 27032319.
  12. ^ a b Hoberman J (21 February 2005). Testosterone Dreams: Rejuvenation, Aphrodisia, Doping. University of California Press. pp. 134–. ISBN 978-0-520-93978-3.
  13. ^ a b Mundy AR, Fitzpatrick J, Neal DE, George NJ (26 July 2010). The Scientific Basis of Urology. CRC Press. pp. 294–. ISBN 978-1-84184-749-8.
  14. ^ a b Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (11 November 2015). Williams Textbook of Endocrinology. Elsevier Health Sciences. pp. 709, 711, 765. ISBN 978-0-323-34157-8.
  15. ^ a b Adis R&D Profile (2004). "Testosterone Undecanoate—Schering AG". Drugs. 5 (6): 368–369. doi:10.2165/00126839-200405060-00012. PMID 15563244.
  16. ^ a b "Testosterone undecanoate - Clarus Therapeutics - AdisInsight".
  17. ^ Köhn, Frank-Michael; Schill, Wolf-Bernhard (November 2003). "A new oral testosterone undecanoate formulation". World Journal of Urology. 21 (5): 311–315. doi:10.1007/s00345-003-0372-x. PMID 14579074.
  18. ^ a b "Testosterone undecanoate depot injection - AdisInsight".
  19. ^ "Testosterone undecanoate - Organon - AdisInsight".
  20. ^ https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022219s000lbl.pdf
  21. ^ Jean L. Fourcroy (27 October 2008). Pharmacology, Doping and Sports: A Scientific Guide for Athletes, Coaches, Physicians, Scientists and Administrators. Routledge. pp. 25–. ISBN 978-1-134-08880-5.
  22. ^ Ong, G. S. Y.; Somerville, C. P.; Jones, T. W.; Walsh, J. P. (2012). "Anaphylaxis Triggered by Benzyl Benzoate in a Preparation of Depot Testosterone Undecanoate". Case Rep Med. 2012: 1–3. doi:10.1155/2012/384054. PMC 3261473. PMID 22272209. 384054.
  23. ^ "Nebido Monograph – Information for Health Care Professionals". Bayer. 2016. Retrieved 19 October 2016.
  24. ^ a b Anita H. Payne; Matthew P. Hardy (28 October 2007). The Leydig Cell in Health and Disease. Springer Science & Business Media. pp. 423–. ISBN 978-1-59745-453-7.
  25. ^ Yeung SJ, Escalante CP, Gagel RF (2009). Medical Care of Cancer Patients. PMPH-USA. pp. 247–. ISBN 978-1-60795-008-0.
  26. ^ a b c d e J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 641–642. ISBN 978-1-4757-2085-3.
  27. ^ a b c d e Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 1002–1004. ISBN 978-3-88763-075-1.
  28. ^ Miriam E. Tucker (March 7, 2014). "FDA Approves Aveed Testosterone Jab, with Restrictions". Medscape. Retrieved December 13, 2016.
  29. ^ a b c I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. ISBN 978-94-011-4439-1.
  30. ^ a b c "Testosterone".
  31. ^ a b c d Nieschlag, Eberhard; Nieschlag, Susan (2017). Testosterone. pp. 1–19. doi:10.1007/978-3-319-46086-4_1. ISBN 978-3-319-46084-0.
  32. ^ a b "Drug Product Database - Health Canada". Health Canada. March 18, 2010. Archived from the original on November 19, 2016. Retrieved November 13, 2016.
  33. ^ Arthur P. Arnold; Donald W. Pfaff; Anne M. Etgen; Susan E. Fahrbach, Robert T. Rubin (10 June 2002). Hormones, Brain and Behavior, Five-Volume Set. Academic Press. pp. 20–. ISBN 978-0-12-532104-4.
  34. ^ Steven B. Karch, MD, FFFLM (21 December 2006). Drug Abuse Handbook, Second Edition. CRC Press. pp. 30–. ISBN 978-1-4200-0346-8.CS1 maint: Multiple names: authors list (link)
  35. ^ 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.

External links

  • Andriol (testosterone undecanoate) - William Llewellyn's Anabolic.org
  • Testosterone undecanoate (intramuscular) - AdisInsight
  • Testosterone undecanoate (oral) - AdisInsight


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