World J Mens Health.  2016 Aug;34(2):65-72. 10.5534/wjmh.2016.34.2.65.

Nonsurgical Interventions for Peyronie's Disease: Update as of 2016

• Joice GA
• Burnett AL

• KMID: 2349843
• DOI: http://doi.org/10.5534/wjmh.2016.34.2.65

Abstract

Peyronie's disease (PD) is a debilitating condition of the penis that leads to significant pain, erectile dysfunction, and emotional distress in men. PD is likely underreported due to lack of knowledge of the disease and the absence of well-established available treatments. Surgical treatment can lead to sustained improvements, but is often associated with penile shortening and places the patient at risk for perioperative morbidity. Nonsurgical management has been studied for several years as an alternative to surgery for men with PD. Currently, much of the data on nonsurgical management is conflicting, with only one treatment that has been recently approved by the US Food and Drug Administration. Significant effort has been devoted to advancing non-surgical treatments for PD that can be implemented outside of the operating room. This review aims to describe the research behind current nonsurgical therapies for PD and to highlight the recent advances that have been made within the last three years.

Keyword

Erectile dysfunction; Injections, intralesional; Penile induration

MeSH Terms

Erectile Dysfunction
Humans
Injections, Intralesional
Male
Operating Rooms
Penile Induration*
Penis
United States Food and Drug Administration

Reference

1. Nehra A, Alterowitz R, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh JJ, et al. Peyronie's disease: AUA guideline. J Urol. 2015; 194:745–753. PMID: 26066402.

2. Somers KD, Dawson DM. Fibrin deposition in Peyronie's disease plaque. J Urol. 1997; 157:311–315. PMID: 8976287.

3. Nelson CJ, Mulhall JP. Psychological impact of Peyronie's disease: a review. J Sex Med. 2013; 10:653–660. PMID: 23153101.

4. Auxilium. Peyronie's Disease Questionnaire (PDQ) [Internet]. Chesterbrook (PA): Auxilium;c2013. cited 2016 Aug 11. Available from: https://urology.jhu.edu/peyronie/peyronie_disease.pdf.

5. Hellstrom WJ, Feldman R, Rosen RC, Smith T, Kaufman G, Tursi J. Bother and distress associated with Peyronie's disease: validation of the Peyronie's disease questionnaire. J Urol. 2013; 190:627–634. PMID: 23376705.

6. Coyne KS, Currie BM, Thompson CL, Smith TM. Responsiveness of the Peyronie's Disease Questionnaire (PDQ). J Sex Med. 2015; 12:1072–1079. PMID: 25664497.

7. Hellstrom WJ, Feldman RA, Coyne KS, Kaufman GJ, Smith TM, Tursi JP, et al. Self-report and clinical response to peyronie's disease treatment: peyronie's disease questionnaire results from 2 large double-blind, randomized, placebo-controlled phase 3 studies. Urology. 2015; 86:291–298. PMID: 26199168.

8. Safarinejad MR, Hosseini SY, Kolahi AA. Comparison of vitamin E and propionyl-L-carnitine, separately or in combination, in patients with early chronic Peyronie's disease: a double-blind, placebo controlled, randomized study. J Urol. 2007; 178:1398–1403. PMID: 17706714.

9. Inal T, Tokatli Z, Akand M, Ozdiler E, Yaman O. Effect of intralesional interferon-alpha 2b combined with oral vitamin E for treatment of early stage Peyronie's disease: a randomized and prospective study. Urology. 2006; 67:1038–1042. PMID: 16581113.

10. Paulis G, Brancato T, D'Ascenzo R, De Giorgio G, Nupieri P, Orsolini G, et al. Efficacy of vitamin E in the conservative treatment of Peyronie's disease: legend or reality? A controlled study of 70 cases. Andrology. 2013; 1:120–128. PMID: 23258640.

11. Ko YH, Moon KH, Lee SW, Kim SW, Yang DY, Moon du G, et al. Urologists' perceptions and practice patterns in Peyronie's disease: a Korean nationwide survey including patient satisfaction. Korean J Urol. 2014; 55:57–63. PMID: 24466399.

12. Dibenedetti DB, Nguyen D, Zografos L, Ziemiecki R, Zhou X. A population-based study of Peyronie's disease: prevalence and treatment patterns in the United States. Adv Urol. 2011; 2011:282503. PMID: 22110491.

13. Ralph DJ, Brooks MD, Bottazzo GF, Pryor JP. The treatment of Peyronie's disease with tamoxifen. Br J Urol. 1992; 70:648–651. PMID: 1486392.

14. Teloken C, Rhoden EL, Grazziotin TM, Ros CT, Sogari PR, Souto CA. Tamoxifen versus placebo in the treatment of Peyronie's disease. J Urol. 1999; 162:2003–2005. PMID: 10569556.

15. Jannetta PJ, Hanafee W, Weidner W, Rosen L. Pneumoencephalographic findings suggesting aneurysm of the vertebral-basilar junction. Differentiation of cases simulating mass lesions. J Neurosurg. 1966; 24:530–535. PMID: 5295918.

16. Park TY, Jeong HG, Park JJ, Chae JY, Kim JW, Oh MM, et al. The efficacy of medical treatment of Peyronie's disease: potassium para-aminobenzoate monotherapy vs. combination therapy with tamoxifen, L-Carnitine, and phosphodiesterase type 5 inhibitor. World J Mens Health. 2016; 34:40–46. PMID: 27169128.

17. Gonzalez-Cadavid NF, Rajfer J. Treatment of Peyronie's disease with PDE5 inhibitors: an antifibrotic strategy. Nat Rev Urol. 2010; 7:215–221. PMID: 20212516.

18. Palmieri A, Imbimbo C, Creta M, Verze P, Fusco F, Mirone V. Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial. Int J Androl. 2012; 35:190–195. PMID: 22085227.

19. Dell'Atti L. Tadalafil once daily and intralesional verapamil injection: a new therapeutic direction in Peyronie's disease. Urol Ann. 2015; 7:345–349. PMID: 26229323.

20. Gelbard MK, Walsh R, Kaufman JJ. Collagenase for Peyronie's disease experimental studies. Urol Res. 1982; 10:135–140. PMID: 6291216.

21. Gelbard MK, James K, Riach P, Dorey F. Collagenase versus placebo in the treatment of Peyronie's disease: a double-blind study. J Urol. 1993; 149:56–58. PMID: 8417217.

22. Gelbard MK, Chagan L, Tursi JP. Collagenase clostridium histolyticum for the treatment of Peyronie's disease: the development of this novel pharmacologic approach. J Sex Med. 2015; 12:1481–1489. PMID: 25940867.

23. Gelbard M, Lipshultz LI, Tursi J, Smith T, Kaufman G, Levine LA. Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. J Urol. 2012; 187:2268–2274. PMID: 22503048.

24. Gelbard M, Goldstein I, Hellstrom WJ, McMahon CG, Smith T, Tursi J, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013; 190:199–207. PMID: 23376148.

25. US Food & Drug Administration (FDA). FDA approves drug treatment for Peyronie's disease [Internet]. Silver Spring (MD): US FDA;c2013. cited 2016 Aug 11. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm377849.htm.

26. Twidwell J, Levine L. Topical treatment for acute phase Peyronie's disease utilizing a new gel, H-100: a randomized, prospective, placebo-controlled pilot study. Int J Impot Res. 2016; 28:41–45. PMID: 26700214.

27. Levine LA, Cuzin B, Mark S, Gelbard MK, Jones NA, Liu G, et al. Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study. J Sex Med. 2015; 12:248–258. PMID: 25388099.

28. Lipshultz LI, Goldstein I, Seftel AD, Kaufman GJ, Smith TM, Tursi JP, et al. Clinical efficacy of collagenase clostridium histolyticum in the treatment of Peyronie's disease by subgroup: results from two large, double-blind, randomized, placebo-controlled, phase III studies. BJU Int. 2015; 116:650–656. PMID: 25711400.

29. Poullis C, Shabbir M, Eardley I, Mulhall J, Minhas S. Clostridium histolyticum collagenase - is this a revolutionary medical treatment for Peyronie's disease? BJU Int. 2016; 118:186–189. PMID: 26683137.

30. Yang KK, Bennett N. Peyronie's disease and injectable collagenase clostridium histolyticum: safety, efficacy, and improvements in subjective symptoms. Urology. 2016; 94:143–147. PMID: 27211926.

31. Ziegelmann MJ, Viers BR, McAlvany KL, Bailey GC, Savage JB, Trost LW. Restoration of penile function and patient satisfaction with intralesional collagenase clostridium histolyticum injection for peyronie's disease. J Urol. 2016; 195:1051–1056. PMID: 26476353.

32. Carson CC 3rd, Sadeghi-Nejad H, Tursi JP, Smith TM, Kaufman GJ, Gilbert K, et al. Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD). BJU Int. 2015; 116:815–822. PMID: 25818264.

33. Levine LA, Larsen SM. Surgical correction of persistent Peyronie's disease following collagenase clostridium histolyticum treatment. J Sex Med. 2015; 12:259–264. PMID: 25345351.

34. Duncan MR, Berman B, Nseyo UO. Regulation of the proliferation and biosynthetic activities of cultured human Peyronie's disease fibroblasts by interferons-alpha, -beta and -gamma. Scand J Urol Nephrol. 1991; 25:89–94. PMID: 1651559.

35. Kendirci M, Usta MF, Matern RV, Nowfar S, Sikka SC, Hellstrom WJ. The impact of intralesional interferon alpha-2b injection therapy on penile hemodynamics in men with Peyronie's disease. J Sex Med. 2005; 2:709–715. PMID: 16422829.

36. Hellstrom WJ, Kendirci M, Matern R, Cockerham Y, Myers L, Sikka SC, et al. Single-blind, multicenter, placebo controlled, parallel study to assess the safety and efficacy of intralesional interferon alpha-2B for minimally invasive treatment for Peyronie's disease. J Urol. 2006; 176:394–398. PMID: 16753449.

37. Stewart CA, Yafi FA, Knoedler M, Mandava SH, McCaslin IR, Sangkum P, et al. Intralesional injection of interferon-α2b improves penile curvature in men with Peyronie's disease independent of plaque location. J Urol. 2015; 194:1704–1707. PMID: 26144333.

38. Levine LA, Merrick PF, Lee RC. Intralesional verapamil injection for the treatment of Peyronie's disease. J Urol. 1994; 151:1522–1524. PMID: 8189561.

39. Chung E, Garcia F, Young LD, Solomon M, Brock GB. A comparative study of the efficacy of intralesional verapamil versus normal saline injection in a novel Peyronie disease animal model: assessment of immunohistopathological changes and erectile function outcome. J Urol. 2013; 189:380–384. PMID: 23174244.

40. Rehman J, Benet A, Melman A. Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term single-blind study. Urology. 1998; 51:620–626. PMID: 9586617.

41. Shirazi M, Haghpanah AR, Badiee M, Afrasiabi MA, Haghpanah S. Effect of intralesional verapamil for treatment of Peyronie's disease: a randomized single-blind, placebo-controlled study. Int Urol Nephrol. 2009; 41:467–471. PMID: 19199072.

42. Favilla V, Russo GI, Privitera S, Castelli T, Madonia M, La Vignera S, et al. Combination of intralesional verapamil and oral antioxidants for Peyronie's disease: a prospective, randomised controlled study. Andrologia. 2014; 46:936–942. PMID: 24124921.

43. Wolff B, Peyronnet B, Cattarino S, Mozer P, Renard-Penna R, Phé V, et al. Intralesional injections for early Peyronie disease: standardized assessment and analysis of predictive factors for treatment response. Urology. 2015; 86:57–61. PMID: 26142583.

44. Levine LA, Costabile RA. Is intralesional verapamil effective therapy for Peyronie's disease? J Urol. 2012; 188:704–706. PMID: 22818342.

45. Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 2011; 91:221–264. PMID: 21248167.

46. Gennaro R, Barletta D, Paulis G. Intralesional hyaluronic acid: an innovative treatment for Peyronie's disease. Int Urol Nephrol. 2015; 47:1595–1602. PMID: 26257044.

47. Zucchi A, Costantini E, Cai T, Cavallini G, Liguori G, Favilla V, et al. Intralesional injection of hyaluronic acid in patients affected with Peyronie's disease: preliminary results from a prospective, multicenter, pilot study. Sex Med. 2016; 4:e83–e88. PMID: 26984291.

48. Muñoz-Rangel CA, Fernandez-Vivar E, Bañuelos-Gallo RA, Gonzalez-Ojeda A, Macias-Amezcua MD, Chavez-Tostado M, et al. Minimally Invasive Therapy Using Intralesional OnabotulinumtoxinA in Peyronie's Disease. Urol J. 2015; 12:2105–2110. PMID: 25923158.

49. Chung E, Brock G. Penile traction therapy and Peyronie's disease: a state of art review of the current literature. Ther Adv Urol. 2013; 5:59–65. PMID: 23372611.

50. Martínez-Salamanca JI, Egui A, Moncada I, Minaya J, Ballesteros CM, Del Portillo L, et al. Acute phase Peyronie's disease management with traction device: a nonrandomized prospective controlled trial with ultrasound correlation. J Sex Med. 2014; 11:506–515. PMID: 24261900.

51. Abern MR, Larsen S, Levine LA. Combination of penile traction, intralesional verapamil, and oral therapies for Peyronie's disease. J Sex Med. 2012; 9:288–295. PMID: 22024053.

52. Yafi FA, Pinsky MR, Stewart C, Sangkum P, Ates E, Trost LW, et al. The effect of duration of penile traction therapy in patients undergoing intralesional injection therapy for peyronie's disease. J Urol. 2015; 194:754–758. PMID: 25804087.

53. Martin DJ, Badwan K, Parker M, Mulhall JP. Transdermal application of verapamil gel to the penile shaft fails to infiltrate the tunica albuginea. J Urol. 2002; 168:2483–2485. PMID: 12441945.

54. Kelsey R. Clinical trials: novel topical gel treatment for Peyronie's disease. Nat Rev Urol. 2016; DOI: 10.1038/nrurol.2016.6.

55. Fojecki GL, Tiessen S, Osther PJ. Extracorporeal shock wave therapy (ESWT) in urology: a systematic review of outcome in Peyronie's disease, erectile dysfunction and chronic pelvic pain. World J Urol. 2016; DOI: 10.1007/s00345-016-1834-2. [Epub].

56. Hatzichristodoulou G, Meisner C, Gschwend JE, Stenzl A, Lahme S. Extracorporeal shock wave therapy in Peyronie's disease: results of a placebo-controlled, prospective, randomized, single-blind study. J Sex Med. 2013; 10:2815–2821. PMID: 23898925.

57. Gao L, Qian S, Tang Z, Li J, Yuan J. A meta-analysis of extracorporeal shock wave therapy for Peyronie's disease. Int J Impot Res. 2016; DOI: 10.1038/ijir.2016.24. [Epub].

58. Castiglione F, Hedlund P, Van der Aa F, Bivalacqua TJ, Rigatti P, Van Poppel H, et al. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie's disease. Eur Urol. 2013; 63:551–560. PMID: 23040209.

59. Gokce A, Abd Elmageed ZY, Lasker GF, Bouljihad M, Braun SE, Kim H, et al. Intratunical injection of genetically modified adipose tissue-derived stem cells with human interferon α-2b for treatment of erectile dysfunction in a rat model of tunica albugineal fibrosis. J Sex Med. 2015; 12:1533–1544. PMID: 26062100.