Erectile dysfunction as an early biomarker of cardiovascular toxicity: Mechanisms and clinical implications.

Erectile dysfunction (ED) has been traditionally regarded as a quality-of-life disorder; however, accumulating evidence positions it as an early and clinically actionable biomarker of cardiovascular toxicity. ED and cardiovascular disease share fundamental pathophysiological mechanisms including endothelial dysfunction, reduced nitric oxide bioavailability, oxidative stress, systemic inflammation, autonomic imbalance, and vascular smooth muscle dysfunction. Because penile cavernosal arteries (~1-2 mm diameter) are substantially smaller than coronary arteries (~3-4 mm), the penile vascular bed manifests endothelial injury earlier, conferring a sentinel role on ED. Two temporally distinct patterns must be recognized: in men with traditional cardiovascular risk factors, ED precedes overt cardiovascular events by 2-5 years, reflecting shared systemic endothelial pathology; whereas drug-induced ED emerges within months to 2 years of therapy initiation, representing an acute or subacute microvascular adverse effect specific to the causative agent. Several drug classes, including anthracycline-based chemotherapy, androgen deprivation therapy, tyrosine kinase inhibitors, VEGF inhibitors, and immune checkpoint inhibitors, induce both cardiovascular toxicity and ED through overlapping microvascular mechanisms, each with a characteristic onset timeline. A structured five-step clinical framework integrating IIEF-5 screening, cardiovascular risk scoring augmented by NT-proBNP and high-sensitivity troponin, ECG-derived diastolic dysfunction indexing, and multimodality imaging including echocardiography with global longitudinal strain, coronary artery calcium scoring, and carotid intima-media thickness is proposed to operationalise ED-guided cardiovascular monitoring. This review highlights mechanistic links, discusses diagnostic and prognostic relevance, and emphasizes multidisciplinary strategies for mitigating long-term cardiovascular outcomes.