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Effects of the recreational use of PDE5 inhibitors on the corpus cavernosum of young, healthy rats



PDE5 inhibitors are widely used for the treatment of erectile dysfunction. However, these drugs have recently become popular among men without erectile dysfunction as a means of enhancing sexual performance and improving sexual desire. The aim of this study was to investigate the histopathological and ultrastructural effects of PDE5 inhibitors on the corpus cavernosum in young, healthy male rats.


Twenty-four 4-month-old male rats were divided into four groups: group 1 was the control group, group 2 rats received sildenafil citrate, group 3 rats received vardenafil hydrochloride, and group 4 rats received tadalafil. All drugs were administered for 4 weeks. Penile tissue was collected for electron microscopy and tissue collagen measurements. Electron microscopic analysis indicated that the number of active fibroblasts and macrophages and the synthesis of new collagen fibers increased in treated rats.


Cavernous tissue collagen levels were significantly higher in the sildenafil-, vardenafil-, and tadalafil-treated groups than in controls (46.16 ± 4.9, 42.06 ± 2.4, 41.07 ± 2.4, and 29.20 ± 3.3, respectively) (p < 0.001).


Young men who use these drugs to enhance performance in the absence of erectile dysfunction may experience irreversible damage to the cavernosal tissue. However, more studies are needed to evaluate the molecular mechanisms by which PDE5 inhibitors affect the corpus cavernosum.

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  1. 1.

    Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170:843–850

  2. 2.

    Burnett AL (1995) Role of nitric oxide in the physiology of erection. Biol Reprod 52:485–489

  3. 3.

    Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ (1996) Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8:47–52

  4. 4.

    Lopez De Leon A, Rojkind M (1985) A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections. J Histochem Cytochem 33:737–743

  5. 5.

    Fox KM, Thadani U, Ma TS (2003) Sildenafil citrate does not reduce exercise tolerance in men with erectile dysfunction and chronic stable angina. Eur Heart J 24:2206–2212

  6. 6.

    Herrmann H, Chang G, Klugher BD, Mahoney PD (2000) Hemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med 342:1622–1626

  7. 7.

    Hatzimouratidis K, Hatzichristou DG (2005) A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs 65:1621–1650

  8. 8.

    Aldridge J, Measham F (1999) Sildenafil (Viagra) is used as a recreational drug in England. BMJ 318:669

  9. 9.

    Bechara A, Casabé A, De Bonis W, Helien A, Bertolino MV (2010) Recreational use of phosphodiesterase type 5 inhibitors by healthy young men. J Sex Med 7:3736–3742

  10. 10.

    Korkes F, Costa-Matos A, Gasperini R, Reginato PV, Perez MDC (2008) Recreational use of PDE5 inhibitors by young healthy men: recognizing this issue among medical students. J Sex Med 5:2414–2418

  11. 11.

    Eloi-Stiven ML, Channaveeraiah N, Christos PJ, Finkel M, Reddy R (2007) Does marijuana use play a role in the recreational use of sildenafil? J Fam Pract 56:E1–E4

  12. 12.

    Abbott D, Comby P, Charuel C, Graepel P, Hanton G (2004) Preclinical safety profile of sildenafil. Int J Impot Res 16:498–504

  13. 13.

    Glenn DR, McVicar CM, McClure N, Lewis SE (2007) Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. Fertil Steril 87:1064–1070

  14. 14.

    Aversa A, Mazzilli F, Rossi T, Delfino M, Isidori AM (2000) Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males. Hum Reprod 15:131–134

  15. 15.

    Pomara G, Morelli G, Canale D, Turchi P, Caglieresi C (2007) Alterations in sperm motility after acute oral administration of sildenafil or tadalafil in young, infertile men. Fertil Steril 88:860–865

  16. 16.

    Pomara G, Morelli G, Menchini-Fabris F, Dinelli N, Campo G, LiGuori G, Selli C (2006) Epistaxis after PDE-5 inhibitors misuse. Int J Impot Res 18:213–214

  17. 17.

    Gonzalez-Cadavid NF, Rajfer J (2010) Treatment of Peyronie’s disease with PDE5 inhibitors: an antifibrotic strategy. Nat Rev Urol 7:215–221

  18. 18.

    Ferrini MG, Kovanecz I, Sanchez S, Vernet D, Davila HH (2007) Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biol Reprod 76:915–923

  19. 19.

    Ferrini MG, Kovanecz I, Nolazco G, Rajfer J, Gonzalez-Cadavid NF (2006) Effects of long-term vardenafil treatment on the development of fibrotic plaques in a rat model of Peyronie’s disease. BJU Int 97:625–633

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All authors declare that there are no competing financial interests.

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Correspondence to Abdulmuttalip Simsek.

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Simsek, A., Tugcu, V., Erturkuner, P. et al. Effects of the recreational use of PDE5 inhibitors on the corpus cavernosum of young, healthy rats. Int Urol Nephrol 46, 1889–1893 (2014). https://doi.org/10.1007/s11255-014-0746-6

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  • PDE5 inhibitors
  • Corpus cavernosum
  • Fibrosis
  • Rat