The Etiology of Peyronie's Disease: Pathogenesis and Genetic Contributions

Introduction: Peyronie's disease (PD) is a chronic fibrosing condition that contributes to penile deformity, curvature, and pain. Initial familial studies demonstrated potential genetic links to PD. Since that time, very few investigations have significantly advanced the science in this area. Hence, there is a large opportunity and significant need to better study the underlying genomics and pathogenesis of PD.

Aim: To summarize the current genomic literature relevant to PD.

Methods: A review was performed of all PubMed-indexed literature from 1970-2018 relating to the pathophysiology and genetics of PD. Key findings were categorically summarized to include epidemiology, risk factors, inheritance patterns, chromosomal instability, genetic associations, epigenetics, differential gene expression, and preclinical models of PD.

Main Outcome Measures: Summary of the current literature on the genetics of PD.

Results: PD is a common condition and has several known risk factors and comorbid disease associations. Although men with PD are believed to be genetically predisposed, there are likely several subtypes of the condition, each with varied pathophysiological disorders and contributing factors. Available data suggest that PD is associated with underlying genetic instability, including dysregulation of genes relating to fibrosis and cellular degradation, thus, resulting in abnormal plaque development and penile deformity. Preclinical models, including cell cultures and rat models, demonstrate several consistencies with PD clinical and histopathologic characteristics; however, an ideal model with spontaneous development of PD is lacking.

Conclusion: Based on limited data, PD likely represents a heterogeneous condition, with both heritable and environmentally-driven epigenetic factors contributing to its development and progression. However, there remains a significant gap in the literature on the underlying cause and pathophysiology of the condition, suggesting a substantial need for further investigation and study. Sharma KL, Alom M, Trost L. The Etiology of Peyronie's Disease: Pathogenesis and Genetic Contributions. Sex Med Rev 2020;8:314-323.