Priapism, defined as a persistent penile erection lasting beyond four hours unrelated to sexual stimulation, is a urological emergency with significant implications for long-term sexual function. Its most common form, ischemic priapism (IP), represents a compartment syndrome of the penis, necessitating immediate intervention to prevent corporal fibrosis and permanent erectile dysfunction. Despite the potentially devastating complications of this condition, management of recurrent priapism episodes historically has commonly involved reactive treatments rather than preventative strategies. This comprehensive narrative review provides a critical analysis of the contemporary understanding of priapism. We delve into the molecular and hemodynamic mechanisms underlying the refined pathophysiological classification: ischemic (low-flow), non-ischemic (high-flow), and stuttering (recurrent) priapism. Recently, increasing elucidation of the complex molecular mechanisms underlying this disorder, principally involving dysregulation of nitric oxide signaling, has allowed for greater insights and exploration into potential therapeutic targets. In this review, we discuss the multiple molecular regulatory pathways implicated in the pathophysiology of priapism. We also identify the roles and mechanisms of molecular effectors in providing the basis for potential future therapies. The review underscores the critical importance of a rapid, systematic diagnostic approach utilizing history, examination, corporal blood gas analysis, and color Doppler ultrasonography. Management is meticulously detailed, emphasizing the stepwise, escalating protocol for IP, from aspiration and sympathomimetic irrigation to surgical shunting, and the conservative or minimally invasive strategies for non-ischemic priapism. A significant focus is placed on the paradigm shift in managing stuttering priapism, where targeted therapies, including the paradoxical use of phosphodiesterase type 5 (PDE5) inhibitors, are revolutionizing prevention. We also explore special populations, long-term sequelae, and future directions, including novel molecular targets, advanced imaging, and regenerative medicine. The objective is to equip clinicians with a sophisticated, evidence-based framework to optimize outcomes in this challenging clinical scenario.
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