https://doi.org/10.4081/aiua.2026.14895
Hyaluronic acid in Peyronie’s disease: focus on injection procedures and clinical practice
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Accepted: 24 February 2026
Published: 28 September 2026
Background: Peyronie's disease is an acquired connective tissue disorder of the tunica albuginea of the corpus cavernosum, characterized by fibrotic plaque formation that impairs normal penile expansion during erection, potentially leading to shaft deformity and erectile dysfunction. Although diagnosis and follow-up are guided by well-established recommendations, significant variability persists in clinical practice regarding intralesional therapy, particularly following the recent introduction of a new hyaluronic acid device for Peyronie’s disease treatment.
Materials and methods: An Italian panel of experts convened to discuss and identify the most appropriate technique for intralesional hyaluronic acid injection in patients with Peyronie’s disease and to review the range of intralesional treatment approaches currently used in Peyronie’s disease.
Results: Both periplaque and intraplaque injection techniques are currently used in everyday clinical practice. Based on the on the panel’s collective clinical experience, periplaque injection may be considered a safe and reproducible option, alongside intraplaque injection, with therapeutic choice depending on patient characteristics and physician expertise.
Conclusions: Hyaluronic acid represents one of the most promising non-surgical treatments for Peyronie’s disease. Both periplaque and intraplaque injection procedures are currently employed in patient management, with periplaque injection emerging as a safe and reproducible approach supported by clinical experience. This work may represent the first systematic effort to describe and compare the different HA injection approaches, providing a valuable contribution toward harmonizing clinical practice and guiding future research.
Downloads
1. Feyisetan O. Cureus. Peyronie's Disease: A Brief Overview. 2023; 15:e37037. DOI: https://doi.org/10.7759/cureus.37037
2. Gabrielsen JS. Peyronie's disease: is it genetic or not? Transl Androl Urol. 2020; 9(Suppl 2): S262-S268. DOI: https://doi.org/10.21037/tau.2019.10.21
3. Abdel Fattah AAE, Diab T, El-Dakhakhny AS, El Hamshary SA. Intralesional injection of hyaluronic acid compared with verapamil in acute phase of Peyronie's disease: A prospective randomized clinical trial. Arab J Urol. 2024; 22:206-211. DOI: https://doi.org/10.1080/20905998.2024.2333583
4. Paulis G, Paulis A, Perletti G. Congenital penile curvature as a possible risk factor for the onset of Peyronie's disease, and psychological consequences of penile curvature. Arch Ital Urol Androl. 2023;95:11238. DOI: https://doi.org/10.4081/aiua.2023.11238
5. La Pera G, Pescatori ES, Calabrese M, et al. SIMONA Study Group. Peyronie's disease: prevalence and association with cigarette smoking. A multicenter population-based study in men aged 50-69 years. Eur Urol. 2001; 40:525-30. DOI: https://doi.org/10.1159/000049830
6. Goldstein I, Hartzell R, Shabsigh R. The impact of Peyronie’s disease on the patient: gaps in our current understanding. Journal of Sex & Marital Therapy. 2016; 42:178-190. DOI: https://doi.org/10.1080/0092623X.2014.985351
7. Nelson CJ, Mulhall JP. Psychological impact of Peyronie’s disease: a review. J Sex Med. 2013; 10:653-660. DOI: https://doi.org/10.1111/j.1743-6109.2012.02999.x
8. Terrier JE, Nelson CJ. Psychological aspects of Peyronie’s disease. Transl Androl Urol. 2016; 5:290-295. DOI: https://doi.org/10.21037/tau.2016.05.14
9. Chung PH, Han TM, Rudnik B, Das AK. Peyronie's disease: what do we know and how do we treat it? Can J Urol. 2020; 27(S3):11-9.
10. Salonia A, Capogrosso P, Boeri L, et al. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2025 Update on Male Hypogonadism, Erectile Dysfunction, Premature Ejaculation, and Peyronie's Disease. Eur Urol. 2025; 88:76-102. DOI: https://doi.org/10.1016/j.eururo.2025.04.010
11. Douroumis K, Kotrotsios K, Katsikatsos P, et al. Acute Phase Peyronie's Disease: Where Do We Stand? Cureus. 2024; 16:e67054. DOI: https://doi.org/10.7759/cureus.67054
12. Mulhall JP, Schiff J, Guhring P. An analysis of the natural history of Peyronie's disease. J Urol. 2006; 175:2115-8. DOI: https://doi.org/10.1016/S0022-5347(06)00270-9
13. Di Maida F, Cito G, Lambertini L, et al. The natural history of Peyronie's disease. World J Mens Health. 2021; 39:399-405. DOI: https://doi.org/10.5534/wjmh.200065
14. Berookhim BM, Choi J, Alex B, Mulhall JP. Deformity stabilization and improvement in men with untreated Peyronie's disease. BJU Int. 2014; 113:133-6. DOI: https://doi.org/10.1111/bju.12346
15. Nelson CJ, Diblasio C, Kendirci M, et al. The chronology of depression and distress in men with Peyronie’s disease. J Sex Med 2008; 5:1985-90. DOI: https://doi.org/10.1111/j.1743-6109.2008.00895.x
16. Garcia Rojo E, García Gómez B, Santos-Pérez de la Blanca R, et al. Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Peyronie's disease: a new diagnostic approach to predict the stage of the disease? Asian J Androl. 2021; 23:325-9. DOI: https://doi.org/10.4103/aja.aja_74_20
17. Lee HY, Pyun JH, Shim SR, Kim JH. Medical Treatment for Peyronie's Disease: Systematic Review and Network Bayesian Meta- Analysis. World J Mens Health. 2024; 42:133-147. DOI: https://doi.org/10.5534/wjmh.230016
18. Li EV, Esterquest R, Pham MN, et al. Peyronie’s disease: pharmacological treatments and limitations. Expert Rev Clin Pharmacol. 2021; 14:703-13. DOI: https://doi.org/10.1080/17512433.2021.1903873
19. Almeida JL, Felício J, Martins FE. Surgical planning and strategies for peyronie’s disease. Sex Med Rev. 2021; 9:478-87. DOI: https://doi.org/10.1016/j.sxmr.2020.07.008
20. Pyrgidis N, Yafi FA, Sokolakis I, et al. Assessment of conservative combination therapies for active and stable peyronie’s disease: a systematic review and meta-analysis. Eur Urol Focus. 2022; 8:1520-30. DOI: https://doi.org/10.1016/j.euf.2021.12.003
21. Minore A, Cacciatore L, Presicce F, et al. Intralesional and topical treatments for Peyronie's disease: a narrative review of current knowledge. Asian J Androl. 2025; 27:156-165. DOI: https://doi.org/10.4103/aja202460
22. Yafi FA, Pinsky MR, Sangkum P, Hellstrom WJG. Therapeutic advances in the treatment of Peyronie’s disease. Andrology. 2015; 3:650-660. DOI: https://doi.org/10.1111/andr.12058
23. Alkandari MH, Touma N, Carrier S. Platelet-rich plasma injections for erectile dysfunction and Peyronie’s disease: a systematic review of evidence. Sexual Medicine Reviews. 2022; 10:341-352. DOI: https://doi.org/10.1016/j.sxmr.2020.12.004
24. Dellis A, Papatsoris A. Stem cell therapy for the treatment of Peyronie’s disease. Expert Opin Biol Ther. 2017; 17:407-413. DOI: https://doi.org/10.1080/14712598.2017.1295034
25. Thomas J, Sencaj M, Ghomeshi A, et al. Stem-cell, shockwave, and platelet rich plasma therapy for the treatment of erectile dysfunction
and Peyronie’s disease: a survey of clinics across the USA. Urology. 2023; 178:83-90. DOI: https://doi.org/10.1016/j.urology.2023.01.061
26. Wayne GF, Cordon BH. Contemporary surgical and non-surgical management of Peyronie’s disease. Transl Androl Urol. 2018; 7:603-17. DOI: https://doi.org/10.21037/tau.2018.04.06
27. Paulis G, Pisano F, Palmieri A, Cai T, et al. Urologists' knowledge base and practice patterns in Peyronie's disease. A national survey of
members of the italian andrology society. Arch Ital Urol Androl. 2021; 93:348-355. DOI: https://doi.org/10.4081/aiua.2021.3.348
28. Wymer K, Kohler T, Trost L. Comparative cost-effectiveness of surgery, collagenase Clostridium histolyticum, and penile traction therapy in men with Peyronie’s disease in an era of effective clinical treatment. J Sex Med. 2019; 16:1421-1432.
29. Guo Y, Yang Y, Mao Q, et al. Efficacy of collagenase Clostridium histolyticum combination therapies for Peyronie's disease: a systematic review and meta-analysis. Sex Med Rev. 2024; 12:497-504. DOI: https://doi.org/10.1093/sxmrev/qeae025
30. Tsambarlis P, Levine LA. Nonsurgical management of Peyronie’s disease. Nat Rev Urol. 2019; 16:172-186. DOI: https://doi.org/10.1038/s41585-018-0117-7
31. Cai T, Tiscione D, Favilla V, et al. Oral administration and intralesional injection of hyaluronic acid versus intralesional injection alone in peyronie’s disease: results from a phase III study. World J Mens Health. 2021; 39:526-32. DOI: https://doi.org/10.5534/wjmh.200048
32. Lumbiganon S, Nakamura H, Hammad MAM, et al. Are patients undergoing intralesional collagenase Clostridium histolyticum injection therapy for Peyronie's disease compliant? A 7-year analysis from a tertiary care men's health center. J Sex Med. 2025; 22:794-798. Erratum in: J Sex Med. 2025; 22:1534. DOI: https://doi.org/10.1093/jsxmed/qdaf051
33. Cocci A, Russo GI, Briganti A, et al. Predictors of treatment success after collagenase Clostridium histolyticum injection for Peyronie's disease: development of a nomogram from a multicentre single-arm, non-placebo controlled clinical study. BJU Int. 2018; 122:680-687. DOI: https://doi.org/10.1111/bju.14410
34. Howell S, Green T, Khalafalla K. Current insights and future directions in Peyronie's disease management: A narrative review. UroPrecision, 2025, 3:3-16. DOI: https://doi.org/10.1002/uro2.104
35. Gelbard M, Goldstein I, Hellstrom WJ, 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. DOI: https://doi.org/10.1016/j.juro.2013.01.087
36. Wymer K, Kohler T, Trost L. Comparative cost-effectiveness of surgery, collagenase Clostridium histolyticum, and penile traction therapy in men with Peyronie’s disease in an era of effective clinical treatment. J Sex Med. 2019; 16:1421-1432. DOI: https://doi.org/10.1016/j.jsxm.2019.06.010
37. Lehner K, Byrne E, Roshandel MR, et al. The discontinuation rate with collagenase Clostridium histolyticum for Peyronie’s disease in a high-volume practice is unexpectedly high: identifying opportunities for patient care improvement. Urology. 2024; 183:121-126. DOI: https://doi.org/10.1016/j.urology.2023.10.022
38. Ahn ST, Moon DG. Collagenase clostridium hystolyticum in the management of Peyronie's disease. Transl Androl Urol. 2017; 6:305-307. DOI: https://doi.org/10.21037/tau.2017.01.15
39. Abdel Raheem A, Johnson M, Abdel-Raheem T, et al. Collagenase clostridium histolyticum in the treatment of Peyronie’s disease-a review of the literature and a new modified protocol. Sex Med Rev 2017; 5:529-35. DOI: https://doi.org/10.1016/j.sxmr.2017.07.005
40. Cocci A, Di Mauro M, Kluth L, et al. Long-Term Outcomes (2 Years) After Hyaluronic Acid Therapy for Peyronie’s Disease. Front. Urol. 2022; 2:929367. DOI: https://doi.org/10.3389/fruro.2022.929367
41. Perovial Package Leaflet Last revision: January 2025.
42. Favilla V, Russo GI, Zucchi A, et al. Evaluation of intralesional injection of HA compared with verapamil in Peyronie’s disease: preliminary results from a prospective, double-blinded, randomized study. Andrology. 2017; 5:771-775. DOI: https://doi.org/10.1111/andr.12368
43. Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev 2011; 91:221-64. DOI: https://doi.org/10.1152/physrev.00052.2009
44. Califano G, Arcaniolo D, Ruvolo CC, et al. Glans penis augmentation: when, how, and why? Int J Impot Res 2022; 34:343-6. DOI: https://doi.org/10.1038/s41443-021-00464-1
45. Romero-Otero J, Manfredi C, Ralph D, et al. Non-invasive and surgical penile enhancement interventions for aesthetic or therapeutic purposes: a systematic review. BJU Int 2021; 127:269-91. DOI: https://doi.org/10.1111/bju.15145
46. Vetrano M, Ranieri D, Nanni M, et al. Hyaluronic Acid (HA), Platelet-Rich Plasm and Extracorporeal Shock Wave Therapy (ESWT) promote human chondrocyte regeneration in vitro and ESWT-mediated increase of CD44 expression enhances their susceptibility to HA treatment. PLoS One. 2019; 14:e0218740. DOI: https://doi.org/10.1371/journal.pone.0218740
47. Cocci A, Di Maida F, Cito G, et al. Comparison of intralesional hyaluronic acid vs. Verapamil for the treatment of acute phase peyronie’s
disease: a prospective, open-label non-randomized clinical study. World J Mens Health. 2020; 39:352-7. DOI: https://doi.org/10.5534/wjmh.190108
48. Capece M, Celentano G, La Rocca R. Current Evidence on the Use of Hyaluronic Acid as Nonsurgical Option for the Treatment of Peyronie’s Disease: A Contemporary Review. Uro 2023; 3:160-167. DOI: https://doi.org/10.3390/uro3020017
49. Gennaro R, Barletta D, Paulis G. Intralesional hyaluronic acid: an innovative treatment for Peyronie's disease.Int Urol Nephrol. 2015; 47:1595-602. DOI: https://doi.org/10.1007/s11255-015-1074-1
50. Zucchi A, Costantini E, Cai T, 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:e83-8. DOI: https://doi.org/10.1016/j.esxm.2016.01.002
51. Cilio S, Rocca R, Celentano G, et al.; YAU Working Group Sexual and Reproductive Health. Intraplaque injections of hyaluronic acid for the treatment of stable-phase Peyronie's disease: a retrospective single-center experience. Asian J Androl. 2024; 26:268-271. DOI: https://doi.org/10.4103/aja202371
Ethics Approval
CRediT authorship contribution
Tommaso Cai contributed to the study conception and to the initial drafting of the manuscript. Marco Falcone performed the literature search, data verification, and contributed to the critical revision of the content. Nicola Mondaini participated in the manuscript revision and in the interpretation of the data. The manuscript was reviewed and approved by Tommaso Cai, Marco Falcone and Nicola Mondaini. All authors read and approved the final version of the manuscript and take full responsibility for the integrity of the work
Supporting Agencies
How to Cite

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.