Testosterone undecanoate was introduced in China for use by injection and in the European Union for use by mouth in the 1970s.[17][18] It became available for use by injection in the European Union in the early to mid 2000s and in the United States in 2014.[19][20] Formulations for use by mouth are approved in the United States.[3][4][21] Along with
testosterone enanthate,
testosterone cypionate, and
testosterone propionate, testosterone undecanoate is one of the most widely used testosterone esters.[15][6][10] 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.[22][8][6][7][10] In addition to its medical use, testosterone undecanoate is used to
improve physique and performance.[10] The drug is a
controlled substance in many countries and so non-medical use is generally illicit.[10]
Oral administration of testosterone undecanoate is an effective method to achieve therapeutic physiological levels of serum testosterone in patients with hypogonadism. In addition, oral therapy has been found to have a positive impact in these patients on quality of life factors such as sexual function, mood, and mental status, as documented in various studies.[23]
Testosterone undecanoate is used in
androgen replacement therapy in men, including
trans-men. It is specifically approved only for the treatment of
hypogonadism.[24][25][26] As an
intramuscular injection, it is administered at a dosage of 1,000 mg (4 mL) once every 3 months.[14] Because of rare occasions of
pulmonary embolism it is not recommended to inject 4 mL of Nebido into one muscle, but to split it into two 2mL injections into left and right counter muscles (e.g.
gluteals).[27]
Conversely,
oral testosterone undecanoate must be taken two or three times a day with food.[14][28]
In the late 1970s, testosterone undecanoate was introduced for oral use in
Europe,[17] although intramuscular testosterone undecanoate had already been in use in
China for several years.[18] Intramuscular testosterone undecanoate was not introduced in Europe and the
United States until much later, in the early to mid 2000s and 2014, respectively.[19][20] Testosterone undecanoate was approved in the United States only in 2014 after three previous rejections due to safety concerns.[35]
Society and culture
Generic names
Testosterone undecanoate is the
generic name of the drug and its
USANTooltip United States Adopted Name and
BANTooltip British Approved Name.[33][34][36][37] It is also referred to as testosterone undecylate.[33][34][36][37]
Brand names
Testosterone undecanoate is or has been marketed under a variety of brand names, including Andriol, Androxon, Aveed, Cernos Depot, Jatenzo, Kyzatrex,[5] Nebido, Nebido-R, Panteston, Reandron 1000, Restandol, Sustanon 250, Undecanoate 250, and Undestor.[33][34][36][38][37]
Oral testosterone undecanoate is available in Europe, Mexico, Asia, and in the United States.[39][40]
Intramuscular testosterone undecanoate has approved in over 100 countries worldwide,[39][10] including
European Union,
Russia and
the USA.[10][39][41] Intramuscular testosterone undecanoate is marketed most commonly as Nebido in Europe and as Aveed in the United States while oral testosterone undecanoate is marketed most commonly as Andriol.[10][39][41] However, as of 2023 Nebido is not on the
formulary of most US hospitals, due to several incidents of
pulmonary embolism that have been reported in the country.
In March 2019, the US
Food and Drug Administration approved testosterone undecanoate (Jatenzo), an oral testosterone capsule to treat men with certain forms of
hypogonadism. These men have low testosterone levels due to specific medical conditions, such as genetic disorders like Klinefelter syndrome or tumors that have damaged the pituitary gland.[21] The FDA granted the approval of Jatenzo to Clarus Therapeutics.[21][44]
In March 2022, testosterone undecanoate (Tlando) was approved for medical use in the United States.[4]
In July 2022, Kyzatrex, an oral testosterone undecanoate capsule, was approved for medical use in the United States.[5] The FDA granted the approval of Kyzatrex to Marius Pharmaceuticals.[45]
Research
Non-alcoholic steatohepatitis
In 2013, a
phase IIclinical trial testing intramuscular testosterone undecanoate for the treatment of
non-alcoholic steatohepatitis (NASH) was initiated in the
United Kingdom.[46] 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.[47]
Osteoporosis
In 2013, a study aimed to evaluate the efficacy of testosterone undecanoate therapy on bone mineral density (BMD) and biochemical markers of bone turnover in elderly males with
osteoporosis and low serum testosterone levels.
They study found that administering low-dose testosterone undecanoate (TU) at a rate of 20 mg per day to elderly men with low serum testosterone and osteoporosis effectively increases bone mineral density in the lumbar spine and femoral neck, and improves bone turnover, similar to the standard-dose TU (40 mg, per day) treatment. The treatment did not exhibit any adverse side effects on the prostate gland, including
prostate-specific antigen. Therefore, low-dose TU appears to be a safe and cost-effective protocol for treating elderly male osteoporosis.[48] However, further clinical trials with larger sample sizes, multiple centers, and long-term follow-ups are required to determine the efficacy and safety of low-dose testosterone undecanoate treatment in elderly male osteoporosis with low serum testosterone.
Health implications
Risks associated with treatment of late-onset hypogonadism
In 2020, a study that evaluated the effects of testosterone therapy in men with testosterone deficiency and varying degrees of weight (normal weight, overweight, and obesity) on anthropometric and metabolic parameters found that long-term testosterone undecanoate therapy in hypogonadal men, regardless of their weight at the start of the study, led to improvements in several body composition parameters, including body weight, waist circumference, and body mass index. Additionally, testosterone undecanoate therapy was found to lower fasting blood glucose and HbA1c levels and improve lipid profiles in this population.[50]
Bone density
There have been several studies that evaluate the effect of testosterone therapy on bone density or
bone mineral density (BMD). One study concluded that long-term testosterone replacement therapy (TRT) in middle-aged men with
late-onset hypogonadism (LOH) and
metabolic syndrome (MS) led to a significant increase in both vertebral and femoral bone mineral density (BMD) after 36 months of treatment, as measured by dual-energy x-ray absorptiometry. The TRT treatment was shown to induce a 5% per year increase in BMD without changes in body mass index (BMI). The study suggests that long-term TRT could be beneficial for improving bone health in middle-aged men with LOH and MS, even in the absence of osteoporosis.[51]
^
abcdeBehre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E (May 1999). "Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies". European Journal of Endocrinology. 140 (5): 414–419.
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PMID10229906.
S2CID22597244.
^Ahmad, Syed W et al. “Is Oral Testosterone the New Frontier of Testosterone Replacement Therapy?.” Cureus vol. 14,8 e27796. 8 Aug. 2022,
doi:10.7759/cureus.27796