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1248, 1254, 1255]. The risk is higher with papaverine-based combinations [1256], while the risk of priapism is
< 1% following prostaglandin E1 injection [1257].

Second-generation antipsychotics (33.8%), other medications (11.3%), and alpha-adrenergic antagonists
(8.8%) accounted for the greatest percentage of published drug-induced priapism cases [1258]. Isolated cases
of priapism have been described in men who have taken Phosphodiesterase Type 5 Inhibitors (PDE5Is) [1243].
A recent study from the U.S. Food and Drug Administration (FDA) Adverse Reporting System Public Dashboard
showed that PDE5Is-induced priapism accounted for only 2.9% of drug-induced priapism. However, most
of these men also had other risk factors for priapism, and it is unclear whether PDE5Is per se can cause
ischaemic priapism [1243]. Since most men who experience priapism following PDE5I treatment have
additional risk factors for ischaemic priapism, PDE5Is use is usually not regarded as a risk factor in itself. In
terms of haemoglobinopathies, SCD is the most common cause of priapism in childhood, accounting for 63%
of cases. It is the primary aetiology in 23% of adult cases [1257], and men with SCD have a lifetime probability
of 29-42% of developing ischaemic priapism [1257, 1259, 1260] (LE: 4).

Mechanisms of SCD-associated priapism may involve derangements of several signalling pathways in the
penis, resulting in disinhibited vasorelaxation of the cavernous smooth muscle by nitric oxide synthase
(NOS) and Rho-associated protein kinase (ROCK) signalling, and increased oxidative stress associated with
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated signalling. Excessive adenosine
and up-regulation of opiorphins in response to hypoxia reduce PDE5 gene expression and activity and impair
NO bioavailability in the penis. Excessive oxidative/nitrosative stress and decreased activity of the RhoA/
Rho-kinase contractile pathway further promotes priapism. Contrary to traditional belief, maintenance of
physiological testosterone levels does not cause priapism, but rather preserves penile homeostasis and
promotes normal erectile function [1261, 1262]. Testosterone deficiency is considered a controversial risk
factor: it is prevalent in patients with SCD, but recent evidence indicates that it is not a risk factor per se for
priapism [1263].

Priapism resulting from metastatic or regional infiltration by tumour is rare and usually reflects an infiltrative
process, more often involving the bladder and prostate as the primary cancer sites [1264]. In a recent large
retrospective study including 412 men with ischaemic priapism, eleven (3.5%) had malignant priapism, of
which seven cases were a consequence of local invasion while the others were secondary to haematological
malignancy [1265]. The conventional therapeutic recommendations for pharmacological treatment are unlikely
to be effective and all of these men should have magnetic resonance imaging (MRI) of the penis and be offered
supportive care and medical intervention for their primary cancer. In selected cases where palliative treatment
options fail to control penile pain, a palliative penectomy can be considered.

Partial priapism, or idiopathic partial segmental thrombosis of the corpus cavemosum, is a rare condition. It is
often classified as a subtype of priapism limited to a single crura without ischaemia, but rather a thrombus is
present within the corpus cavernosum. Its aetiology is unknown, but bicycle riding, trauma, drug use, sexual
intercourse, haematological diseases and α-blockers intake have all been associated with partial segmental
thrombosis [1266]. The presence of a congenital web within the corpora is also a risk factor [1267].

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