Priapism in Sickle Cell Disease: New Aspects of Pathophysiology

Priapism is a prolonged, persistent, and painful penile erection unassociated with sexual interest or stimulation, which affects a large percentage of male sickle cell disease (SCD) patients. It manifests either as an acute, severe event, or as recurrent, stuttering priapism, with very limited therapeutic options. Untreated priapism can cause irreversible erectile dysfunction and surgical treatment remains the only option for severe cases. The mechanisms that contribute to the development of sickle cell disease-associated priapism are not fully understood, precluding efficacious pharmacological approaches. In this chapter, we review the physiology of penile erection, definitions of priapism, and summarize current knowledge of the pathophysiology underlying SCD-associated priapism. We discuss current and future possible therapeutic interventions, with emphasis on dysregulated signaling pathways that contribute to the development of this complication, such as the nitric oxide/cyclic guanosine monophosphate system and the RhoA/ROCK system, as well as the role of adenosine, opiorphins, and androgens in the pathogenesis of priapism.