Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

JATENZO®: Challenges in the development of oral testosterone

International Journal of Impotence Research volume 34, pages 721–724 (2022)Cite this article

Subjects

Abstract

Testosterone therapy (TT) for the treatment of testosterone deficiency (TD) can be administered via several routes of administration. Due to a variety of concerns such as hepatotoxicity, an oral formulation has long been absent in the United States. Recently, JATENZO® (testosterone undecanoate) oral capsules was approved by the US FDA as an oral option for men suffering from TD. In this article, we will discuss the history and challenges in the development of a viable oral formulation of exogeneous TT and examine how JATENZO® addresses these concerns.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Molecular structure of testosterone with modifications to improve tolerability of oral formulations.
Fig. 2: Pictorial representation of TU lymphatic absorption after oral delivery in SEDDS formulation.

Similar content being viewed by others

References

  1. Davidson JM, Camargo CA, Smith ER. Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab. 1979;48:955–8.

    Article  CAS  PubMed  Google Scholar 

  2. Finkelstein JS, Klibanski A, Neer RM, Greenspan SL, Rosenthal DI, Crowley WF Jr. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Ann Intern Med. 1987;106:354–61.

    Article  CAS  PubMed  Google Scholar 

  3. Jockenhovel F, Vogel E, Reinhardt W, Reinwein D. Effects of various modes of androgen substitution therapy on erythropoiesis. Eur J Med Res. 1997;2:293–8.

    CAS  PubMed  Google Scholar 

  4. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996;81:4358–65.

    CAS  PubMed  Google Scholar 

  5. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000;85:2670–7.

    CAS  PubMed  Google Scholar 

  6. Mulhall JP, Trost LW, Brannigan RE, Kurtz EG, Redmon JB, Chiles KA, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200:423–32.

    Article  PubMed  Google Scholar 

  7. Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92:4241–7.

    Article  CAS  PubMed  Google Scholar 

  8. Araujo AB, O’Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89:5920–6.

    Article  CAS  PubMed  Google Scholar 

  9. Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, Williams RE, et al. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab. 2008;93:3870–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lokeshwar SD, Patel P, Fantus RJ, Halpern J, Chang C, Kargi AY, et al. Decline in serum testosterone levels among adolescent and young adult men in the USA. Eur Urol Focus. 2020.

  11. Bandari J, Ayyash OM, Emery SL, Wessel CB, Davies BJ. Marketing and testosterone treatment in the USA: a systematic review. Eur Urol Focus 2017;3:395–402.

    Article  PubMed  Google Scholar 

  12. Edel Y, Sagy I, Pokroy-Shapira E, Oren S, Dortort Lazar A, Egbaria M, et al. A cross-sectional survey on the preference of patients with rheumatoid arthritis for route of administration of disease-modifying anti-rheumatic drugs: oral target-specific versus parenteral biologic. Isr Med Assoc J. 2020;22:154–9.

    PubMed  Google Scholar 

  13. Sanchez Martinez I, Cerdan Sanchez M, Lopez Roman J, Iniesta Martinez F, Carreon-Guarnizo E, Meca Lallana JE, et al. Possible influence of the route of treatment administration on treatment adherence in patients with multiple sclerosis. Clin Ther. 2020;42:e87–e99.

    Article  PubMed  Google Scholar 

  14. Shoskes JJ, Wilson MK, Spinner ML. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol. 2016;5:834–43.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ishak KG. Hepatic neoplasms associated with contraceptive and anabolic steroids. Recent Results Cancer Res. 1979;66:73–128.

    CAS  PubMed  Google Scholar 

  16. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154:502–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Westaby D, Ogle SJ, Paradinas FJ, Randell JB, Murray-Lyon IM. Liver damage from long-term methyltestosterone. Lancet. 1977;2:262–3.

    CAS  PubMed  Google Scholar 

  18. Bagatell CJ, Bremner WJ. Androgen and progestagen effects on plasma lipids. Prog Cardiovasc Dis. 1995;38:255–71.

    Article  CAS  PubMed  Google Scholar 

  19. Delorimier AA, Gordan GS, Lowe RC, Carbone JVMethyltestosterone. Related steroids, and liver function. Arch Intern Med. 1965;116:289–94.

    Article  CAS  PubMed  Google Scholar 

  20. Foss GL, Simpson SL. Oral methyltestosterone and jaundice. Br Med J. 1959;1:259–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hild SA, Attardi BJ, Koduri S, Till BA, Reel JR. Effects of synthetic androgens on liver function using the rabbit as a model. J Androl. 2010;31:472–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1715–44.

    Article  PubMed  Google Scholar 

  23. Nieschlag E, Mauss J, Coert A, Kicovic P. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol. 1975;79:366–74.

    Article  CAS  Google Scholar 

  24. Skakkebaek NE, Bancroft J, Davidson DW, Warner P. Androgen replacement with oral testosterone undecanoate in hypogonadal men: a double blind controlled study. Clin Endocrinol. 1981;14:49–61.

    Article  CAS  Google Scholar 

  25. Nieschlag E, Behre HM, Bouchard P, Corrales JJ, Jones TH, Stalla GK, et al. Testosterone replacement therapy: current trends and future directions. Hum Reprod Update. 2004;10:409–19.

    Article  CAS  PubMed  Google Scholar 

  26. Yoshida EM, Erb SR, Scudamore CH, Owen DA. Severe cholestasis and jaundice secondary to an esterified testosterone, a non-C17 alkylated anabolic steroid. J Clin Gastroenterol. 1994;18:268–70.

    Article  CAS  PubMed  Google Scholar 

  27. Legros JJ, Meuleman EJ, Elbers JM, Geurts TB, Kaspers MJ, Bouloux PM, et al. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Eur J Endocrinol. 2009;160:821–31.

    Article  CAS  PubMed  Google Scholar 

  28. Yin AY, Htun M, Swerdloff RS, Diaz-Arjonilla M, Dudley RE, Faulkner S, et al. Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation. J Androl. 2012;33:190–201.

    Article  CAS  PubMed  Google Scholar 

  29. Swerdloff RS, Dudley RE. A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men. Ther Adv Urol. 2020;12:1756287220937232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Swerdloff RS, Wang C, White WB, Kaminetsky J, Gittelman MC, Longstreth JA, et al. A new oral testosterone undecanoate formulation restores testosterone to normal concentrations in hypogonadal men. J Clin Endocrinol Metab. 2020;105:2515–31.

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Mehul Patel

  2. Department of Urology, Georgetown University School of Medicine, Washington DC, USA

    Akhil Muthigi

  3. Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA

    Ranjith Ramasamy

Authors
  1. Mehul Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akhil Muthigi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ranjith Ramasamy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehul Patel.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, M., Muthigi, A. & Ramasamy, R. JATENZO®: Challenges in the development of oral testosterone. Int J Impot Res 34, 721–724 (2022). https://doi.org/10.1038/s41443-021-00461-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41443-021-00461-4

This article is cited by

Search

Advanced search

Quick links