What causes clitoral priapism in female-to-male (FTM) patients on testosterone cypionate (testosterone) 100 mg weekly?

Clitoral Priapism in FTM Patients on Testosterone Cypionate

Mechanism of Testosterone-Induced Clitoral Priapism

Testosterone cypionate causes clitoral priapism in FTM patients through androgenic stimulation of clitoral erectile tissue, leading to prolonged engorgement and veno-occlusive mechanisms similar to penile ischemic priapism. 1

The FDA label for testosterone cypionate explicitly warns that "priapism or excessive sexual stimulation may develop" during androgen therapy, and recommends stopping the androgen if this effect appears. 1 While the label primarily addresses penile priapism, the underlying mechanism applies to clitoral tissue, which is embryologically homologous to penile erectile tissue and contains similar vascular structures capable of engorgement. 2

Pathophysiologic Mechanisms

The development of clitoral priapism in FTM patients on testosterone involves several key mechanisms:

• Direct androgenic stimulation: Testosterone increases clitoral size (clitoromegaly) and enhances erectile tissue responsiveness, predisposing to prolonged engorgement episodes. 1

• Veno-occlusive dysfunction: Similar to ischemic penile priapism, clitoral priapism involves failure of normal detumescence mechanisms, with blood becoming trapped in engorged clitoral tissue. 3

• Alpha-adrenergic effects: Testosterone may alter the balance of vasoconstrictor and vasodilator mechanisms in clitoral erectile tissue, impairing normal return to flaccid state. 4

Clinical Presentation

FTM patients experiencing clitoral priapism will present with:

• Prolonged clitoral engorgement lasting >4 hours, unrelated to sexual stimulation 3, 2
• Pain and tenderness of the clitoris and immediately adjacent tissue 4, 5
• Swelling of the clitoral area 4, 6
• Local irritation without resolution 6

Critical Distinction from Other Causes

While most reported cases of clitoral priapism are medication-induced (particularly by psychotropic drugs with alpha-adrenergic blockade like trazodone), 4, 7 testosterone represents a unique etiology through direct androgenic stimulation rather than alpha-blockade. 1 This is an important distinction because:

• Testosterone-induced priapism results from excessive androgenic stimulation rather than vascular blockade 1
• The FDA specifically identifies this as a known adverse effect requiring dose reduction or discontinuation 1
• Unlike drug-induced cases from alpha-blockers, testosterone causes structural clitoral enlargement that may predispose to recurrent episodes 1

Management Approach

The primary intervention is reducing or temporarily discontinuing testosterone cypionate, as recommended by the FDA label. 1

Specific management steps include:

1. Immediate testosterone dose reduction or cessation: The FDA label explicitly states "if any of these effects appear, the androgen should be stopped and if restarted, a lower dosage should be utilized." 1

2. Symptomatic relief measures:

   • Oral pseudoephedrine (alpha-adrenergic agonist) has shown effectiveness in clitoral priapism resolution 7
   • Local ice packs for symptomatic relief 5
   • Analgesics (opiates or NSAIDs) for pain management 5

3. Consider adjunctive therapy: Imipramine has been used in some cases, though withdrawal of the causative agent remains the focal point. 4

Dosing Considerations

At 100 mg weekly, this patient is receiving a standard masculinizing dose of testosterone cypionate. 1 The FDA label warns that "oligospermia may occur after prolonged administration of excessive dosage," suggesting dose-dependent effects. 1 For FTM patients experiencing priapism, options include:

• Dose reduction to 50-75 mg weekly
• Temporary cessation until symptoms resolve completely
• Restart at lower dose only after complete resolution 1

Prevention of Recurrence

Patients should be counseled that priapism is a known adverse effect of testosterone therapy that requires immediate dose adjustment. 1 They should be instructed to report:

• Too frequent or persistent erections/engorgement 1
• Any clitoral pain or swelling lasting >4 hours 3
• Changes requiring urgent evaluation before permanent tissue damage occurs 3

The testosterone dose should be titrated to the lowest effective level that achieves masculinization goals while avoiding this complication. 1