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.

  • Original Article
  • Published:

Combination therapy of testosterone enanthate and tadalafil on PDE5 inhibitor non-reponders with severe and intermediate testosterone deficiency

International Journal of Impotence Research volume 25, pages 29–33 (2013)Cite this article

Subjects

Abstract

Several studies have suggested combination therapy with testosterone supplementation in patients not responding to PDE5 inhibitors. Considering the pathophysiological basis for testosterone supplementation, the present study aims to identify whether combination therapy allows persistence of treatment effect after testosterone discontinuation. Furthermore, we evaluated whether the degree of testosterone depletion affects treatment outcome from combination therapy. Hypogonadal patients (<350 ng dl−1) with erectile dysfunction who previously did not respond to PDE5 inhibitors were treated with testosterone enanthate injections and daily tadalafil. Patients were stratified into two groups depending on the level of testosterone deficiency, with 250 ng dl−1 as a reference point. Following testosterone supplementation (12 weeks) and combination therapy (12 weeks), patients with severe testosterone deficiency showed higher IIEF (International Index of Erectile Function) erectile function (EF) domain score (16.47±4.019 vs 12.36±4.051, P=0.001) and more patients responding satisfactorily to treatment by general assessment (57.9 vs 16.0%, P=0.009), despite reaching similar levels of serum total testosterone (602±169 ng dl−1 vs 698±165 ng dl−1, P=0.057). Testosterone supplementation was then discontinued and patients were maintained only on daily tadalafil (12 weeks). The severe depletion group maintained higher EF domain scores than baseline (13.06±3.38 vs 7.20±2.24, P=0.0004), despite testosterone levels returning to baseline. The results suggest that combination therapy was more beneficial to patients with severe testosterone depletion, possibly by improving underlying pathophysiology.

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Boulton A, Selam JL, Sweeney M, Ziegler D . Sildenafil citrate for the treatment of erectile dysfunction in men with type II diabetes mellitus. Diabetologia 2001; 44: 1296–1301.

    Article  CAS  Google Scholar 

  2. Shabsigh R, Kaufman J, Steidle C, Padma-Nathan H . Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004; 172: 658–663.

    Article  CAS  Google Scholar 

  3. Greenstein A, Mabjeesh NJ, Sofer M, Kaver I, Matzkin H, Chen J . Does sildenafil combined with testosterone gel improve erectile dysfunction in hypogonadal men in whom testosterone supplement therapy alone failed? J Urol 2005; 173: 530–532.

    Article  CAS  Google Scholar 

  4. Kalinchenko S, Kozlov G, Gontcharov N, Katsiya G . Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Aging Male 2003; 6: 94–99.

    Article  CAS  Google Scholar 

  5. Greco EA, Spera G, Aversa A . Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur Urol 2006; 50: 940–947.

    Article  CAS  Google Scholar 

  6. Lu YL, Kuang L, Zhu H, Wu H, Wang XF, Pang YP et al. Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5¥á-reductase inhibitor. Asian J Androl 2007; 9: 843–847.

    Article  CAS  Google Scholar 

  7. Shabsigh R . The effects of testosterone on the cavernous tissue and erectile function. World J Urol 1997; 15: 21–26.

    Article  CAS  Google Scholar 

  8. Salehian B, Wang C, Alexander G, Davidson T, McDonald V, Berman N et al. Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate--a clinical research center study. J Clin Endocrinol Metab 1995; 80: 3567–3575.

    CAS  PubMed  Google Scholar 

  9. Aversa A, Bruzziches R, Greco E, Pili M, Spera G . Possible involvement of gonadic steroids in determining erectile response to pharmacoerection test in men with erectile dysfunction. It J Sex Reprod Med 2006; 13: 3–9.

    Google Scholar 

  10. Morales A, Heaton JPW . Hormonal erectile dysfunction: evaluation and management. Urol Clin North Am 2001; 28: 279–288.

    Article  CAS  Google Scholar 

  11. Traish A, Saad F, Guay A . The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl 2009; 30: 23–32.

    Article  CAS  Google Scholar 

  12. Zhang XH, Filippi S, Morelli A, Vignozzi L, Luconi M, Donati S et al. Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J Sex Med 2006; 3: 253–266.

    Article  CAS  Google Scholar 

  13. Cummings M, Alexander W . Erectile dysfunction in patients with diabetes. Hosp Med 1999; 60: 638–644.

    Article  CAS  Google Scholar 

  14. Seftel AD, Sun P, Swindle R . The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 2004; 171: 2341–2345.

    Article  Google Scholar 

  15. Group UKPDS. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br Med J 1998; 317: 703–713.

    Article  Google Scholar 

  16. Zitzmann M, Faber S, Nieschlag E . Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 2006; 91: 4335–4343.

    Article  CAS  Google Scholar 

  17. Zitzmann M, Nieschlag E . The CAG repeat polymorphism within the androgen receptor gene and maleness1. Int J Androl 2003; 26: 76–83.

    Article  CAS  Google Scholar 

  18. Zitzmann M, Gromoll J, Von Eckardstein A, Nieschlag E . The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia 2003; 46: 31–39.

    Article  CAS  Google Scholar 

  19. Jockenhovel F, Minnemann T, Schubert M, Freude S, Hubler D, Schumann C et al. Comparison of long-acting testosterone undecanoate formulation versus testosterone enanthate on sexual function and mood in hypogonadal men. Eur J Endocrinol 2009; 160: 815–819.

    Article  CAS  Google Scholar 

  20. Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A . Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol 2003; 58: 632–638.

    Article  CAS  Google Scholar 

  21. Shamloul R, Ghanem H, Fahmy I, El-Meleigy A, Ashoor S, Elnashaar A et al. Testosterone therapy can enhance erectile function response to sildenafil in patients with PADAM: a pilot study. J Sex Med 2005; 2: 559–564.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Korea University College of Medicine, Guro Hospital, Seoul, Korea

    J W Kim, M M Oh & D G Moon

  2. Department of Urology, Inje University College of Medicine, Seoul Paik Hospital, Seoul, Korea

    M G Park

  3. Department of Urology, Korea University College of Medicine, Ansan Hospital, Ansan, Korea

    J Y Park & J H Bae

  4. Department of Urology, Korea University College of Medicine, Asam Hospital, Seoul, Korea

    J J Kim

Authors
  1. J W Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M M Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M G Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Y Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J H Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J J Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D G Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D G Moon.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, J., Oh, M., Park, M. et al. Combination therapy of testosterone enanthate and tadalafil on PDE5 inhibitor non-reponders with severe and intermediate testosterone deficiency. Int J Impot Res 25, 29–33 (2013). https://doi.org/10.1038/ijir.2012.32

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijir.2012.32

Keywords

This article is cited by

Search

Advanced search

Quick links