Hydroxyzine and Erectile Dysfunction
Hydroxyzine does not cause erectile dysfunction; rather, it has been associated with the opposite problem—priapism (prolonged, painful erections)—particularly when combined with other medications that have alpha-adrenergic blocking properties.
Mechanism of Action
Hydroxyzine is an antihistamine with notable alpha-adrenergic antagonist activity, which can paradoxically promote rather than inhibit erections 1, 2. This alpha-blocking property relaxes penile vascular smooth muscle and enhances arterial inflow, potentially leading to prolonged erections rather than erectile dysfunction 3.
Clinical Evidence
Case Reports of Priapism
Multiple documented cases exist of hydroxyzine causing priapism (erections lasting >4 hours), including:
- A 35-year-old male on stable risperidone who developed priapism requiring intracavernosal phenylephrine after adding hydroxyzine 50 mg nightly for 10 days 1
- A case of hydroxyzine overdose (200-600 mg) resulting in ischemic priapism with severely abnormal blood gas analysis (pH 6.736) requiring aspiration and 560 μg intracavernosal phenylephrine 2
The molecular structure of hydroxyzine's metabolite (norchlorcyclizine) resembles trazodone's metabolite (m-chlorophenylpiperazine), suggesting a shared mechanism for inducing erections 3
Absence of ED Reports
In a comprehensive analysis of the FDA Adverse Event Reporting System (FAERS) database from 2010-2020, which identified 6,142 reports of medication-associated erectile dysfunction, hydroxyzine was not among the 20 medications most commonly associated with ED 4
The medications that dominated ED reports were 5-alpha reductase inhibitors (46% of reports) and neuropsychiatric medications (40%), particularly SSRIs—not antihistamines like hydroxyzine 4
Clinical Implications
Risk Assessment
- The primary sexual side effect concern with hydroxyzine is priapism, not erectile dysfunction, especially when combined with:
Patient Counseling
Patients starting hydroxyzine, particularly those on concurrent medications with alpha-blocking properties, should be warned about the risk of prolonged erections requiring emergency intervention 1, 2
If priapism occurs (erection >4 hours), immediate medical attention is required to prevent corporal tissue damage 5
Common Pitfalls
Do not confuse hydroxyzine with medications that actually cause erectile dysfunction, such as:
- SSRIs (particularly paroxetine with 70.7% incidence) 6
- Beta-blockers and thiazide diuretics 7, 8
- Typical antipsychotics that elevate prolactin 7
If a patient on hydroxyzine reports erectile dysfunction, evaluate other causes including diabetes, hypertension, cardiovascular disease, metabolic syndrome, or concomitant medications known to cause ED 7, 8.