A narrative review of pathophysiology and therapeutic concepts in Peyronie’s disease

Saveliy Kelebeyev, Kristian Black, Raevti Bole, Petar Bajic^*
Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA
* Corresponding Author: Petar Bajic. Email: email

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.079756

Received 27 January 2026; Accepted 28 April 2026; Published online 11 June 2026

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Abstract

Peyronie’s disease (PD) is an acquired connective tissue disorder characterized by fibrotic plaque formation within the tunica albuginea that can significantly impair sexual function and quality of life. Despite being described over 280 years ago, its pathophysiology remains incompletely understood, contributing to variable and often limited efficacy of nonsurgical therapies. PD is a multifactorial condition resulting from the interaction of mechanical injury, metabolic comorbidities, and individual susceptibility, with genetic contributions supported by familial clustering, associations with fibroproliferative disorders, and emerging cytogenetic and epigenetic data. At the molecular level, PD reflects dysregulated wound healing characterized by persistent myofibroblast activation, impaired extracellular matrix turnover, and sustained transforming growth factor-β-mediated profibrotic signaling. These insights support a phase-based clinical framework, with active-phase focused on pain control, penile traction, and intralesional injections, and surgical intervention reserved for stable-phase disease with functionally significant deformity. Among nonsurgical options, collagenase clostridium histolyticum has the strongest evidence for curvature reduction, while other emerging therapies remain investigational. Surgery remains the most reliable option for severe PD, with evolving techniques aimed at correcting complex deformities while preserving penile length and girth. The purpose of this narrative review is to provide a unified framework for PD assessment and treatment by integrating current evidence on pathophysiology, contemporary non-surgical and surgical management, and patient selection strategies.