Testosterone undecanoate

Testosterone undecanoate, sold for use by mouth under the brand names Andriol and Jatenzo and for use by injection under the brand names Aveed, Nebido and Reandron, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men.,[4][2][5][6] which includes hormone therapy for transgender men.[7][8][9] It is taken by mouth two to three times per day with food or given by injection into muscle once every 8 to 12 weeks, depending on individual response.[6][10]

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 namesOral: Andriol, Jatenzo, others
IM: Aveed, Nebido, others
Other namesTU; Testosterone undecylate; Testosterone 17β-undecanoate; ORG-538; CLR-610
AHFS/Drugs.comMonograph
MedlinePlusa614041
License data
Pregnancy
category
Routes of
administration
By mouth, intramuscular injection
Drug classAndrogen; Anabolic steroid; Androgen ester
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: 3–7%[citation needed]
Intramuscular: high
Protein bindingHigh (testosterone)
MetabolismLiver
MetabolitesTestosterone, undecanoic acid, metabolites of testosterone
Elimination half-lifeIn TSO: 20.9 days (i.m.)[2][3]
In CO: 33.9 days (i.m.)[2][3]
Excretion~90% Urine, 6% feces
Identifiers
  • [(8R,9S,10R,13S,14S,17S)-10,13-Dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] undecanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.025.193 Edit this at Wikidata
Chemical and physical data
FormulaC30H48O3
Molar mass456.711 g·mol−1
3D model (JSmol)
  • CCCCCCCCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C
  • InChI=1S/C30H48O3/c1-4-5-6-7-8-9-10-11-12-28(32)33-27-16-15-25-24-14-13-22-21-23(31)17-19-29(22,2)26(24)18-20-30(25,27)3/h21,24-27H,4-20H2,1-3H3/t24-,25-,26-,27-,29-,30-/m0/s1 ☒N
  • Key:UDSFVOAUHKGBEK-CNQKSJKFSA-N ☒N
  (verify)

Side effects of testosterone undecanoate include symptoms of masculinization like acne, increased hair growth, voice changes, hypertension, elevated liver enzymes, hypertriglyceridemia, and increased sexual desire.[6] The drug is a prodrug of testosterone, the biological ligand of the androgen receptor (AR) and hence is an androgen and anabolic steroid.[11][6] It has strong androgenic effects and moderate anabolic effects, which make it useful for producing masculinization and suitable for androgen replacement therapy.[6] Testosterone undecanoate is a testosterone ester and a prodrug of testosterone in the body.[5][4][2] Because of this, it is considered to be a natural and bioidentical form of testosterone.[12]

Testosterone undecanoate was introduced in China for use by injection and in Europe for use by mouth in the 1970s.[13][14] It became available for use by injection in Europe in the early to mid 2000s and in the United States in 2014.[15][16] As of 2019, a formulation for use by mouth has been approved in the United States - Jatenzo.[17] Along with testosterone enanthate, testosterone cypionate, and testosterone propionate, testosterone undecanoate is one of the most widely used testosterone esters.[11][2][6] 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.[18][4][2][3][6] In addition to its medical use, testosterone undecanoate is used to improve physique and performance.[6] The drug is a controlled substance in many countries and so non-medical use is generally illicit.[6]

Medical dosageEdit

Testosterone undecanoate is used in androgen replacement therapy. It is specifically approved only for the treatment of hypogonadism.[19][20][21] As an intramuscular injection, it is administered at a dosage of 1,000 mg once every 12 weeks.[10] Conversely, oral testosterone undecanoate must be taken two or three times a day with food.[10][22]

Side effectsEdit

Side effects of testosterone undecanoate include virilization among others.[6]

AnaphylaxisEdit

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 in Reandron 1000, benzyl benzoate has been reported as a cause of anaphylaxis (a serious life-threatening allergic reaction) in a case in Australia.[23] 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.[24] In Australia, reports to the Adverse Drug Reactions Advisory Committee (ADRAC), which evaluates reports of adverse drug reactions for the Therapeutic Goods Administration (TGA), show several reports of allergic reactions since the anaphylaxis case from 2011.[citation needed]

PharmacologyEdit

PharmacodynamicsEdit

Androgenic vs. anabolic activity
of androgens/anabolic steroids
Medication Ratioa
Testosterone ~1:1
Androstanolone (DHT) ~1:1
Methyltestosterone ~1:1
Methandriol ~1:1
Fluoxymesterone 1:1–1:15
Metandienone 1:1–1:8
Drostanolone 1:3–1:4
Metenolone 1:2–1:30
Oxymetholone 1:2–1:9
Oxandrolone 1:3–1:13
Stanozolol 1:1–1:30
Nandrolone 1:3–1:16
Ethylestrenol 1:2–1:19
Norethandrolone 1:1–1:20
Notes: In rodents. Footnotes: a = Ratio of androgenic to anabolic activity. 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).

PharmacokineticsEdit

Testosterone undecanoate has a very long elimination half-life and mean residence time when given as a depot intramuscular injection.[25][2][3] 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.[2][3] 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).[25] Testosterone undecanoate is administered via intramuscular injection once every three months or so.[10][26]

ChemistryEdit

Testosterone undecanoate, or testosterone 17β-undecanoate, is a synthetic androstane steroid and a derivative of testosterone.[27][28] It is an androgen ester; specifically, it is the C17β undecylate (undecanoate) ester of testosterone.[27][28] A related testosterone ester with a similarly very long duration is testosterone buciclate.[4][5]

HistoryEdit

In the late 1970s, testosterone undecanoate was introduced for oral use in Europe,[13] although intramuscular testosterone undecanoate had already been in use in China for several years.[14] Intramuscular testosterone undecanoate was not introduced in Europe and the United States until much later, in the early to mid 2000s and 2014, respectively.[15][16] Testosterone undecanoate was approved in the United States after three previous rejections due to safety concerns.[29]

Society and cultureEdit

Generic namesEdit

Testosterone undecanoate is the generic name of the drug and its USAN and BAN.[27][28][30][31] It is also referred to as testosterone undecylate.[27][28][30][31]

Brand namesEdit

Testosterone undecanoate is or has been marketed under a variety of brand names, including Andriol, Androxon, Aveed, Cernos Depot, Jatenzo, Nebido, Nebido-R, Panteston, Reandron 1000, Restandol, Undecanoate 250, and Undestor.[27][28][30][32][31]

AvailabilityEdit

Intramuscular testosterone undecanoate is available in the United States, Canada, Europe, and elsewhere in the world.[6][33][34] It is approved in over 100 countries worldwide.[33][6] Oral testosterone undecanoate is available in Canada, Europe, Mexico, Asia, and elsewhere but not in the United States.[33][35] 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.[6][33][34]

Legal statusEdit

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.[36][37]

ResearchEdit

Non-alcoholic steatohepatitisEdit

In 2013, a phase II clinical trial testing intramuscular testosterone undecanoate for the treatment of non-alcoholic steatohepatitis (NASH) was initiated in the United Kingdom.[38] In the United States in 2018, Lipocine Inc. began investigating the potential of using an oral testosterone undecanoate formulation, known as LPCN-1144, in patients with NASH.[39]

Oral testosterone undecanoateEdit

Recently, two different oral formulations of testosterone undecanoate were developed for the treatment of hypogonadism in the United States.[40][41]

On March 27, 2019, the United States Food and Drug Administration (FDA) approved Jatenzo (testosterone undecanoate), an oral testosterone capsule to treat men with certain forms of hypogonadism. The FDA granted the approval of Jatenzo to Clarus Therapeutics.[42] Clarus has stated it expects Jatenzo to be available in United States pharmacies before the end of 2019,[43] however, it is unclear when Jatenzo will be available for sale as it is currently the subject of a lawsuit alleging patent infringement.[44] The suit was filed by Lipocine Inc., who has also developed an oral testosterone undecanoate drug, Tlando, which (as of May 2019) is under review at the FDA.[45]

ReferencesEdit

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External linksEdit