Bridging fibrosis and function: an integrated mechanistic and therapeutic framework for Peyronie's disease and related erectile dysfunction.

INTRODUCTION: Peyronie's disease (PD) and erectile dysfunction (ED) are prevalent and frequently coexisting male sexual disorders that share endothelial dysfunction, oxidative stress, and tunical fibrosis as common pathophysiologic pathways. Recognizing their interconnected nature has reframed both conditions within a unified model of penile vascular-fibrotic disease. OBJECTIVES: To synthesize recent advances in the mechanistic, diagnostic, and therapeutic understanding of PD and ED, and to propose an integrated framework for comprehensive sexual medicine care. METHODS: A integrative narrative review of contemporary clinical studies, translational studies, molecular studies and guideline recommendations was conducted to evaluate epidemiologic trends, shared molecular mechanisms, and evolving therapeutic modalities addressing both PD and ED. RESULTS: Up to 60% of PD patients experience concomitant ED. Both disorders are linked by endothelial nitric oxide synthase dysregulation, oxidative stress, and transforming growth factor-β1-mediated fibrosis. Diagnostic evaluation now integrates penile duplex Doppler ultrasonography, elastography, and psychometric tools to assess vascular, structural, and psychosexual domains. Therapeutic strategies increasingly adopt multimodal approaches: phosphodiesterase-5 inhibitors improve hemodynamics and may attenuate early fibrotic activity; intralesional therapy remains central to nonsurgical management, with collagenase Clostridium histolyticum as the established standard for plaque remodeling and adjunct injectables such as verapamil, interferon-α2b, and hyaluronic acid providing additional anti-inflammatory or antifibrotic benefits, particularly in the active phase; and low-intensity shockwave therapy promotes angiogenesis and tissue recovery. Regenerative therapies-including stem cell, exosome, and gene-targeted interventions-offer promising disease-modifying potential. Surgery (plication, grafting, or prosthesis implantation) remains definitive for refractory cases, complemented by psychosexual rehabilitation. CONCLUSIONS: PD and ED represent a shared vascular-fibrotic spectrum requiring integrated, mechanism-driven management. Emerging regenerative and molecular therapies, supported by artificial intelligence-assisted diagnostics and digital health tools, signal a paradigm shift toward personalized, holistic restoration of structure, function, and intimacy.