Current Sexual Health Reports

, Volume 1, Issue 3, pp 109–114 | Cite as

Evolution of delivery systems for testosterone administration

  • Joel M. Kaufman
Article

Abstract

Hypogonadism, especially in aging men, is being identified and treated more frequently. Androgen replacement therapy began in the 1930s, and oral and intramuscular testosterone preparations were the primary products until the 1980s. Because of toxicity with oral medications and serum levels outside the normal range with injectable preparations, alternative approaches have been developed. Outside the United States, many patients receive oral testosterone undecanoate, which requires multiple doses per day and produces inconsistent serum levels. Transdermal preparations, both patches and gels, provide excellent serum levels and safety, although patches may cause skin irritation. Implantable pellets and buccal tablets provide additional choices for androgen replacement. Testosterone gel provides excellent patient tolerability and efficacy with somewhat higher costs and low potential for transfer to contacts.

Keywords

Testosterone Testosterone Replacement Therapy Testosterone Enanthate Testosterone Undecanoate Buccal Tablet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Elbers JMH, Grootenhuis AJ: New tissue-selective androgens: perspectives in the treatment of androgen deficits. Ann Endocrinol 2003, 64:183–189.Google Scholar
  2. 2.
    Velázquez E, Bellabara Arata G: Testosterone replacement therapy. Arch Androl 1998, 41:79–90.PubMedGoogle Scholar
  3. 3.
    Gambineri A, Pasquali R: Testosterone therapy in men: clinical and pharmacological perspectives. J Endocrinol Invest 2000, 23:196–214.PubMedGoogle Scholar
  4. 4.
    Howell S, Shalet S: Testosterone deficiency and replacement. Horm Res 2001, 56(suppl 1):86–92.PubMedCrossRefGoogle Scholar
  5. 5.
    Morley JE, Perry HM III: Androgen deficiency in aging men: role of testosterone replacement therapy. J Lab Clin Med 2000, 135:370–378.PubMedCrossRefGoogle Scholar
  6. 6.
    Freeman ER, Bloom DA, McGuire EJ: A brief history of testosterone. J Urol 2001, 165:371–373.PubMedCrossRefGoogle Scholar
  7. 7.
    Vest SA, Howard JE: Clinical experiments with androgens, IV: A method of implantation of crystalline testosterone. JAMA 1939, 13:1869–1872.Google Scholar
  8. 8.
    Gruenewald DA, Matsumoto AM: Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc 2003, 51:101–115. Excellent review of ART including MEDLINE search of placebo-controlled, double-blind prospective trials through October 2001.PubMedCrossRefGoogle Scholar
  9. 9.
    Matsumoto AM: Hormonal therapy of male hypogonadism. Endocrinol Metab Clin North Am 1994, 23:857–875.PubMedGoogle Scholar
  10. 10.
    Thompson PD, Cullinane EM, Sady SP, et al.: Contrasting effects of testosterone and stanozol on serum lipoprotein levels. JAMA 1989, 261:1165–1168.PubMedCrossRefGoogle Scholar
  11. 11.
    de Lorimier AA, Gordan GS, Lowe RC, et al.: Methyltestosterone, related steroids and liver function. Arch Intern Med 1965, 116:289–294.Google Scholar
  12. 12.
    Henderson JT, Richmond J, Sumerling MD: Androgenic-anabolic steroid therapy and hepatocellular carcinoma. Lancet 1973, 2:934.CrossRefGoogle Scholar
  13. 13.
    Morales A, Johnson B, Heaton JWP, et al.: Oral androgens in the treatment of hypogonadal impotent men. J Urol 1994, 152:1115–1118.PubMedGoogle Scholar
  14. 14.
    Wang C, Swerdloff RS: Testosterone undecanoate and testosterone cyclodextrin. In Pharmacology, Biology and Clinical Applications of Androgens: Current Status and Future Prospects. Edited by Basin S, Gabelnick HL, Spieler JM, et al. New York: Wiley-Liss; 1995:487–491.Google Scholar
  15. 15.
    Gooren LJG: A ten-year safety study of the oral androgen testosterone undecanoate. J Androl 1994, 15:212–215.PubMedGoogle Scholar
  16. 16.
    Morales A, Johnston B, Heaton JPW, et al.: Testosterone supplementation for hypogonadal impotence: assessment of biochemical measures and therapeutic outcomes. J Urol 1997, 157:849–854.PubMedCrossRefGoogle Scholar
  17. 17.
    Bagchus WM, Hurst R, Maris F, et al.: Important effect of food on the bioavailability of oral testosterone undecanoate. Pharmacotherapy 2003, 23:319–325.PubMedCrossRefGoogle Scholar
  18. 18.
    Dobs AS, Hoover DR, Chen M-C: Pharmacokinetic characteristics, efficacy and safety of buccal testosterone in hypogonadal males: a pilot study. J Clin Endocrinol Metab 1998, 83:33–39.PubMedCrossRefGoogle Scholar
  19. 19.
    Ross RJM, Jabbar A, Jones TH, et al.: Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in hypogonadal men. Eur J Endocrinol 2004, 150:57–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Korbonitis M, Slawik M, Cullen D, et al.: A comparison of a novel testosterone bioadhesive buccal tablet Striant with a testosterone adhesive patch in hypogonadal males. J Clin Endocrinol Metab 2004, 89:2039–2043.CrossRefGoogle Scholar
  21. 21.
    Dobs AS, Matsumoto AM, Wang C, et al.: Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men. Curr Med Res Opinions 2004, 20:729–738.CrossRefGoogle Scholar
  22. 22.
    Snyder PJ, Lawrence DA: Treatment of male hypogonadism with testosterone enanthate. J Clin Endocrinol Metab 1980, 51:1335–1339.PubMedGoogle Scholar
  23. 23.
    Sokol RZ, Palacios A, Campfield LA, et al.: Comparison of the kinetics of injectable testosterone in eugonadal and hypogonadal men. Fertil Steril 1982, 37:425–430.PubMedGoogle Scholar
  24. 24.
    Wang C: Androgen delivery systems: overview of existing methods and applications. In Pharmacology, Biology and Clinical Applications of Androgens: Current Status and Future Prospects. Edited by Bhasin S, Gabelnick HL, Spieler JM, et al. New York: Wiley-Liss; 1995:433–435.Google Scholar
  25. 25.
    Dobs AS, Meikle AW, Arver S, et al.: Pharmacokinetics, efficacy and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 1999, 84:3469–3483. Randomized multicenter parallel-group comparison of IM and nonscrotal transdermal testosterone patch with pharmacokinetic and clinical evaluation.PubMedCrossRefGoogle Scholar
  26. 26.
    Cantrill JA, Dewis P, Large DM, et al.: Which testosterone replacement therapy? Clin Endocrinol 1984, 21:97–107.Google Scholar
  27. 27.
    Handelsman DJ, Conway AJ, Boylan LM: Pharmacokinetics and pharmacodynamics of testosterone pellets in man. J Clin Endocrinol Metab 1990, 70:216–222.Google Scholar
  28. 28.
    Jockenhövel F, Vogel E, Kruetzer M, et al.: Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men. Clin Endocrinol 1996, 45:61–71.CrossRefGoogle Scholar
  29. 29.
    Testopel™ pellets. In Physicians Desk Reference; 2002:3610–3611.Google Scholar
  30. 30.
    Cunningham GR, Snyder PJ, Atkinson LE: Testosterone transdermal delivery system. In Pharmacology, Biology and Clinical Applications of Androgens: Current Status and Future Prospects. Edited by Basin S, Gabelnick HL, Spieler JM, et al. New York: Wiley-Liss; 1995:437–447.Google Scholar
  31. 31.
    Findlay JC, Place VA, Snyder PJ: Transdermal delivery of testosterone. J Clin Endocrinol Metab 1987, 64:266–268.PubMedGoogle Scholar
  32. 32.
    Cunningham GR, Cordero E, Thorby JI: Testosterone replacement with transdermal therapeutic systems. JAMA 1989, 261:2525–2530.PubMedCrossRefGoogle Scholar
  33. 33.
    Ahmed SR, Boucher AE, Manni A, et al.: Transdermal testosterone therapy in the treatment of male hypogonadism. J Clin Endocrinol Metab 1988, 66:546–551.PubMedCrossRefGoogle Scholar
  34. 34.
    McClure RD, Oses R, Ernest ML: Hypogonadal impotence treated by transdermal testosterone. Urology 1991, 37:224–228.PubMedCrossRefGoogle Scholar
  35. 35.
    Snyder PJ, Peachey H, Hanneush P, et al.: Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 1999, 84:2647–2653.PubMedCrossRefGoogle Scholar
  36. 36.
    Meikle AW, Mazer NA, Moellmer JF, et al.: Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992, 74:623–628.PubMedCrossRefGoogle Scholar
  37. 37.
    Meikle AW, Arver S, Dobs AS, et al.: Androderm™: a permeation enhanced non-scrotal testosterone transdermal system for the treatment of male hypogonadism. In Pharmacology, Biology and Clinical Applications of Androgens: Current Status and Future Prospects. Edited by Bhasin S, Gabelnick HL, Spieler JM, et al. New York: Wiley-Liss; 1995:449–459.Google Scholar
  38. 38.
    Arver S, Dobs AS, Meikle AW, et al.: Long-term efficacy and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men. Clin Endocrinol 1997, 47:727–737.CrossRefGoogle Scholar
  39. 39.
    Jordan WPJr: Allergy and topical irritation associated with transdermal testosterone administration: a comparison of scrotal and nonscrotal transdermal system. Am J Contact Dermat 1997, 8:108–113.PubMedCrossRefGoogle Scholar
  40. 40.
    McClellan KJ, Goa KL: Transdermal testosterone. Drugs 1998, 55:253–259.PubMedCrossRefGoogle Scholar
  41. 41.
    Jordan WP Jr, Atkinson LE, Lai C: Comparison of the skin irritation potential of two testosterone transdermal systems: an investigational system and a marketed product. Clin Ther 1998, 20:80–87.PubMedCrossRefGoogle Scholar
  42. 42.
    Testoderm TTS. In Physicians Desk Reference; 2002:574–576.Google Scholar
  43. 43.
    Yu Z, Gupta SK, Hwang SS, et al.: Transdermal testosterone administration in hypogonadal men: comparison of pharmacokinetics at different sites of application and at the first and fifth days of application. J Clin Pharmacol 1997, 37:1129–1138.PubMedGoogle Scholar
  44. 44.
    Wang C, Berman N, Longstreth JA, et al.: Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a general clinical research center study. J Clin Endocrinol Metab 2000, 85:964–976.PubMedCrossRefGoogle Scholar
  45. 45.
    Wang C, Swerdloff RS, Iranmanesh A, et al.: Transdermal testosterone gel improves sexual function, muscle strength and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000, 85:2839–2853. Pivotal trial of most commonly prescribed testosterone replacement preparations in the United States, including comparison with the testosterone patch.PubMedCrossRefGoogle Scholar
  46. 46.
    Swerdloff RS, Wang C, Cunningham G, et al.: Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000, 85:4500–4510.PubMedCrossRefGoogle Scholar
  47. 47.
    Rolf C, Knie U, Lemnitz G, et al.: Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation. Clin Endocrinol 2002, 56:637–641.CrossRefGoogle Scholar
  48. 48.
    Marbury T, Hamill E, Bachand R, et al.: Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim®, compared to AndroGel®. Biopharm Drug Dispos 2003, 24:115–120.PubMedCrossRefGoogle Scholar
  49. 49.
    Steidle C, Schwartz S, Jacoby K, et al.: AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 2003, 88:2673–2681.PubMedCrossRefGoogle Scholar
  50. 50.
    Testim® and Striant®. The Medical Letter 2003, 45:70–72.Google Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Joel M. Kaufman
    • 1
  1. 1.Urology Research OptionsAuroraUSA

Personalised recommendations