Discussion
The epidemiology of PDE5i-induced priapism is poorly understood, and the evidence is confined to primarily case reports.1–3.We have performed an extensive study on the association between PDE5i consumption and the risk of priapism, with relatively high number of cases. We also present the first epidemiologic reports of PDE5i-induced priapism among children and adolescents.
A recent study on the U.S. Food and Drug Administration (FDA) Adverse Reporting System Public Dashboard has found that priapism accounts for 0.7% of all ADRs recorded for PDE5i consumers not diagnosed with sickle cell disease (SCD), which is a known risk factor for priapism. We found a similar global incidence (0.4%) with respect to the international population sampled by the VigiBase database. Further, we estimate the proportion to be lower given that we have not excluded SCD cases, which have a higher incidence of priapism at baseline. Additionally, in VigiBase, it is not clear if the reported priapism events are ischemic or are solely selected based on the time length of a prolonged erection. This could further contribute to an even lower incidence for true ischemic priapism in our data.
Priapism can occur at any age, most frequently affecting men over fifty. However, in children and adolescents, priapism is rare, and data on its epidemiology is scarce and inconsistent, partly due to variation in priapism’s definition. SCD is the leading etiology behind childhood priapism compared to pharmacological agents in adults. Nevertheless, the same drugs responsible for drug-induced priapism in adults are capable of causing priapism in children, and PDE5is at therapeutic doses are thought to induce priapism in 1% of cases. Likewise, we found the incidence of priapism among all reported ADRs to be 1.16% in consumers under eighteen years old, which is three times higher than in older patients. PDE5is tendency to cause priapism decreases with age, possibly due to alterations in tissue characteristics of penile nerves, blood vessels, and corpus spongiosum, resulting in higher rates of ED and decreasing the response to PDE5i agents.
PDE5is, specifically sildenafil and tadalafil, have been widely used to treat pulmonary arterial hypertension (PAH) in children and adolescents. Likewise, our data showed that the majority of male individuals under eighteen consume PDE5is for pulmonary hypertension. Although ED in teenagers is a relatively established entity, its incidence is not well-studied. Most cases are thought to be due to psychogenic and vasculogenic etiologies and are routinely referred for related work up. As of today, no PDE5i is approved for the treatment of ED in adolescents; nevertheless, its recreational use has been reported by some studies. In a survey of forty-three teenage males who self-identified as “lifetime sildenafil citrate users”, it was shown that as many as nine percent had started abusing the product since the age of fourteen and that curiosity and peer pressure were the two most frequent contributory factor for the initial use. In our study, ED was also among the top indications for using PDE5i in the twelve to eighteen age group. Although PDE5is are prescription drugs in the US, they are available over the counter in other parts of the world and it is unclear if the drug was obtained under the treatment of a physician or not in our set of cases. However, our results favor the highly selected use of these products for the enhancement of erection in adolescents, given that priapism at young age potentially has everlasting impacts on sexual health.25