Intralesional injection of the calcium channel blocker Verapamil in Peyronie's disease: A critical review


Submitted: January 18, 2020
Accepted: February 17, 2020
Published: October 2, 2020
Abstract Views: 3085
PDF: 15
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Authors

  • Murad Asali Assuta Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
  • Muhammad Asali International School of Economics, Tbilisi, Georgia; IZA, Bonn, Germany; and School of International and Public Affairs, Columbia University, United States.

Objective: To assess the effectiveness of an intralesional injection of verapamil in men with Peyronie’s disease (PD).
Materials and Methods: The data provided in the current review are based on a thorough review of the available original articles on PD retrieved with a systematic literature search using PubMed- Medline, and the Cochrane Central Register of Controlled Trials, up to December 2019, to identify studies dealing with Peyronie’s disease and its treatment. Included were only original articles, that we thoroughly evaluated. We searched for the primary and secondary terms of: “Peyronie’s disease,” “Penile curvature,” “Erectile dysfunction,” “Verapamil and Peyronie’s disease,” “Calcium channel blocker,” and “Intralesional injection.”
Results: The initial search of the databases yielded a total of 1240 studies (PubMed: 1058; Cochrane: 182), as of December 2019. Seventy studies were removed due to duplication. Further 986 studies were removed due to not being in English (except for one study by Arena F. for which we got a translation form Italian), being about animal experimentations, not being full-text, and not being clinical trials. Likewise, studies not referring at all to verapamil were excluded (148). From the remaining 36 full-text articles we focused on 13 studies which met the inclusion criteria, mainly being deemed relevant to the context of this study.
Conclusions: Calcium channel blockers have been shown in both in vitro and in vivo studies to inhibit the synthesis and secretion of extracellular matrix molecules, as well as to increase collagenase activity. Patients with localised plaque are the best candidates for intralesional injections of verapamil. The beneficial effects of intralesional verapamil are apparent within the first three months. For patients who respond to treatment, the injections should be continued for six months. Patients who fail to respond to intralesional verapamil or whose angulation is greater than 30° at presentation should be considered candidates for surgery. Injection of verapamil is clinically safe for patients with Peyronie’s disease, and it appears to induce a rapid, beneficial effect in patients for the reduction of plaque size. Intralesional verapamil injection for Peyronie’s disease could reduce pain, decrease penile curvature, and improve sexual function.


De La Peyronie F. Sur quelques obstacles qui s’opposent al’ejaculation naturelle de la semence. Mem de l’Acad Roy de Chir. 1743; 1:425– 434.

Schwarzer U, Sommer F, Klotz T, Braun M, Reifenrath B, Engelmann U. The prevalence of Peyronie’s disease: results of a large survey. BJU Int. 2001; 88(7):727–730. DOI: https://doi.org/10.1046/j.1464-4096.2001.02436.x

Mulhall JP, Creech SD, Boorjian SA, et al. Subjective and objective analysis of the prevalence of Peyronie’s disease in a population of men presenting for prostate cancer screening. J Urol. 2004; 171(6 pt 1):2350–2353 DOI: https://doi.org/10.1097/01.ju.0000127744.18878.f1

Williams JL, Thomas GG. The natural history of Peyronie’s disease. J Urol. 1970; 103(1):75–76 DOI: https://doi.org/10.1016/S0022-5347(17)61894-9

Gelbard MK, Dorey F, James K. The natural history of Peyronie’s disease. J Urol. 1990; 144(6):1376–1379. DOI: https://doi.org/10.1016/S0022-5347(17)39746-X

Kadioglu A, Tefekli A, Erol B, Oktar T, Tunc M, Tellaloglu S. A retrospective review of 307 men with Peyronie’s disease; results of a large survey. J Urol. 2002; 168(3):1075-1079. DOI: https://doi.org/10.1016/S0022-5347(05)64578-8

Stojić M, Negrojević M, Josić P, Stojić S. Conservative therapy of Peyronie’s disease using vitamin E. Med Pregl. 1987; 40:133–135.

Akkus E, Carrier S, Rehman J, Breza J, Kadioglu A, Lue TF. Is colchicine effective in Peyronie’s disease? A pilot study. Urology. 1994; 44:291–295. DOI: https://doi.org/10.1016/S0090-4295(94)80155-X

Teloken C, Rhoden EL, Grazziotin TM, Ros CT, Sogari PR, Souto CA. Tamoxifen vs placebo in the treatment of Peyronie’s disease. J Urol. 1999; 162:2003– 2005. DOI: https://doi.org/10.1016/S0022-5347(05)68087-1

Carson CC. Potassium para-aminobenzoate for the treatment of Peyronie’s disease: is it effective? Tech Urol. 1997; 3:135–139.

Gelbard MK, James K, Riach P, Dorey F. Collagenase vs placebo in the treatment of Peyronie’s disease: a double-blind study. J Urol. 1993; 149:56–58. DOI: https://doi.org/10.1016/S0022-5347(17)35998-0

Di Stasi SM, Giannantoni A, Stephen RL, et al. A prospective, randomized study using transdermal electromotive administration of verapamil and dexamethasone for Peyronie’s disease. J Urol. 2004; 171(4):1605–1608. DOI: https://doi.org/10.1097/01.ju.0000116450.82816.2c

Primus G. Orgotein in the treatment of plastic induration of the penis (Peyronie’s disease). Int Urol Nephrol. 1993; 25:169 –172.

Ahuja S, Bivalacqua TJ, Case J, Vincent M, Sikka SC, Hellstrom WJ. A pilot study demonstrating clinical benefit from intralesional interferon alpha 2B in the treatment of Peyronie’s disease. J Androl. 1999; 20:444–448.

Levine LA. Treatment of Peyronie’s disease with intralesional verapamil injection. J Urol. 1997; 158:1395–1399. DOI: https://doi.org/10.1016/S0022-5347(01)64224-1

Levine LA, Merrick PF, Lee RC. Intralesional verapamil injection for the treatment of Peyronie’s disease. J Urol. 1994; 151:1522–1524. DOI: https://doi.org/10.1016/S0022-5347(17)35291-6

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. DOI: https://doi.org/10.1016/S0090-4295(97)00700-0

Levine LA, Goldman KE. Updated experience with intralesional verapamil injection treatment for Peyronie’s disease. J Urol. 2000; 163:170, abstract 751.

Bittard H, Schraub S, Bittard M. Treatment of Peyronie’s disease by a combination of radiotherapy and surgery. Apropos of 51 cases. Ann Urol. 1988; 22:67–69.

Busetto GM. Extracorporeal shock wave therapy in the treatment of Peyronie's disease: Long- term results. Arch Ital Urol Androl. 2010; 82(2):128-33.

Kelly RB. Pathways of protein secretion in eukaryotes. Science. 1985; 230:25– 32. DOI: https://doi.org/10.1126/science.2994224

Askey DB, Miller EA, Holguin MA, Albertini D.F. The effect of weak electric fields and verapamil on exocytosis in human fibroblasts. J Cell Biology. 1988; 107:336a, abstract 1905.

Kappas AM, Barsoum GH, Ortiz JB, Keighley MR. Prevention of peritoneal adhesions in rats with verapamil, hydrocortisone sodium succinate, and phosphatidylcholine. Eur J Surg. 1992; 158:33–35.

Lee RC, Doong H, Jellema, AF. The response of burn scars to intralesional verapamil. Report of five cases. Arch Surg. 1994; 129:107–111. DOI: https://doi.org/10.1001/archsurg.1994.01420250119015

Anderson MS, Shankey TV, Lubrano T, Mulhall JP. Inhibition of Peyronie’s plaque fibroblast proliferation by biologic agents. Int J Impot Res. 2000; 12 (Suppl 3): S25 – S31. DOI: https://doi.org/10.1038/sj.ijir.3900558

Arena F. Clinical effects of verapamil in the treatment of Peyronie’s disease. Acta Biomed Ateneo Parmense. 1995; 66:269–272.

Teloken C. Objective evaluation of non-surgical approach for Peyronie’s disease. J Urol. 1996; 155:633A, abstract 1290.

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(6):2483–2485. DOI: https://doi.org/10.1016/S0022-5347(05)64173-0

Greenfield JM, Shah SJ, Levine LA. Verapamil versus saline in electromotive drug administration for Peyronie's disease: a double-blind, placebo controlled trial. J Urol. 2007; 177(3):972-5. DOI: https://doi.org/10.1016/j.juro.2006.10.065

Trost LW, Gur S, Hellstrom WJ. Pharmacological Management of Peyronie's Disease. Drugs. 2007; 67(4):527-45. DOI: https://doi.org/10.2165/00003495-200767040-00004

Abern MR, Larsen S, Levine LA. Combination of Penile Traction, Intralesional Verapamil, and Oral Therapies for Peyronie's Disease. J Sex Med. 2012; 9(1):288-95. DOI: https://doi.org/10.1111/j.1743-6109.2011.02519.x

Moncada I, Krishnappa P, Romero J, Torremade J, Fraile A, Martinez-Salamanca JI, Porst H, Levine L. Penile traction therapy with the new device 'Penimaster PRO' is effective and safe in the stable phase of Peyronie's disease: a controlled multicentre study. BJU Int. 2019;123(4):694-702. doi: 10.1111/bju.14602. DOI: https://doi.org/10.1111/bju.14602

Cowper MG, Burkett CB, Le TV, Scherzer N, Hellstrom WJG. Penile Stretching as a Treatment for Peyronie's Disease: A Review. Sex Med Rev. 2019;7(3):508-515. doi: 10.1016/j.sxmr.2018.11.002. DOI: https://doi.org/10.1016/j.sxmr.2018.11.002

Rice PG, Somani BK, Rees RW. Twenty Years of Plaque Incision and Grafting for Peyronie's Disease: A Review of Literature. Sex Med. 2019;7(2):115-128. doi: 10.1016/j.esxm.2019.01.001. DOI: https://doi.org/10.1016/j.esxm.2019.01.001

Barbosa ARG, Takemura LS, Cha JD, et al.Surgical Treatment of Peyronie's Disease: Systematic Review of Techniques Involving or Not Tunica Albuginea Incision. Sex Med Rev. 2019 Sep 27. pii: S2050-0521(19)30082-4. doi: 10.1016/j.sxmr.2019.08.002. [Epub ahead of print] DOI: https://doi.org/10.1016/j.sxmr.2019.08.002

Porst H, Burri A; European Society for Sexual Medicine (ESSM) Educational Committee. Current Strategies in the Management of Peyronie's Disease (PD)-Results of a Survey of 401 Sexual Medicine Experts Across Europe. J Sex Med. 2019;16(6):901-908. doi: 10.1016/j.jsxm.2019.03.404. DOI: https://doi.org/10.1016/j.jsxm.2019.03.404

Song KM, Chung DY, Choi MJ, et al. Vactosertib, a Novel, Orally Bioavailable Activin Receptor-Like Kinase 5 Inhibitor, Promotes Regression of Fibrotic Plaques in a Rat Model of Peyronie's Disease. World J Mens Health. 2019; doi: 10.5534/wjmh.190071. DOI: https://doi.org/10.5534/wjmh.190071

Lee RC, Ping JA. Calcium antagonists retard extracellular matrix production in connective tissue equivalent. J Surg Res. 1990; 49:463–466. DOI: https://doi.org/10.1016/0022-4804(90)90197-A

Asali, M., & Asali, M. (2020). Intralesional injection of the calcium channel blocker Verapamil in Peyronie’s disease: A critical review. Archivio Italiano Di Urologia E Andrologia, 92(3). https://doi.org/10.4081/aiua.2020.3.253

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