What is the likelihood of erectile dysfunction in a male patient with hypertension, possibly with Benign Prostatic Hyperplasia (BPH), taking Perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor) 8 mg per day?

Likelihood of Erectile Dysfunction with Perindopril 8 mg Daily

Perindopril 8 mg daily has a very low likelihood of causing erectile dysfunction—ACE inhibitors like perindopril are among the least likely antihypertensive drug classes to impair erectile function and may even be protective compared to diuretics or beta-blockers. 1

Evidence from Major Clinical Trials

The EUROPA trial specifically evaluated perindopril 8 mg daily (the exact dose in question) in 12,218 patients over 4.2 years and demonstrated significant cardiovascular benefits without reporting erectile dysfunction as a notable adverse effect. 1 This large-scale trial provides direct evidence that this specific dose is well-tolerated regarding sexual function.

Comparative Risk Among Antihypertensive Classes

ACE inhibitors consistently show the lowest rates of erectile dysfunction among major antihypertensive drug classes:

• Thiazide diuretics carry the highest risk, with chlorthalidone showing a 17.1% incidence of erection problems at 24 months versus 8.1% with placebo in the TOMHS trial (P = 0.025). 1, 2

• Beta-blockers (except nebivolol) are associated with increased erectile dysfunction, with 71% of hypertensive men on traditional beta-blockers experiencing some degree of ED. 3

• ACE inhibitors (including perindopril, enalapril, lisinopril) show no increased incidence of erectile dysfunction compared to placebo in multiple controlled trials. 1, 2

• In the VA Cooperative trial, ACE inhibitors demonstrated no difference in sexual dysfunction incidence compared to placebo. 1

Mechanistic Considerations

The protective effect of ACE inhibitors relates to their favorable impact on endothelial function rather than impairing it. 1, 4 Since erectile dysfunction and hypertension share endothelial dysfunction as a common pathophysiologic mechanism, ACE inhibitors may actually improve the vascular substrate necessary for normal erectile function. [4, @12@]

Clinical Context: BPH Considerations

If the patient has concurrent BPH symptoms, this creates an important clinical decision point:

• Alpha-blockers (doxazosin, terazosin) may offer dual benefits for both hypertension and BPH while showing the lowest rates of erectile dysfunction among all antihypertensive classes—in TOMHS, doxazosin had the lowest incidence of ED and the highest rate of improvement in men with baseline ED. 1, 2

• Perindopril remains an excellent choice and can be combined with alpha-blockers if needed for BPH symptoms. 1

Management Algorithm if ED Develops

If erectile dysfunction emerges after starting perindopril, consider these steps before attributing it to the medication:

1. Evaluate other contributing factors first 1, 2:

   • Progression of underlying vascular disease (hypertension itself causes ED in 67-68% of hypertensive men) 5
   • Uncontrolled diabetes or new-onset glucose intolerance
   • Depression or psychological factors
   • Other medications (especially if beta-blockers or diuretics were added)
   • Heavy alcohol use
   • Relationship issues

2. Check testosterone levels if ED persists, as hypogonadism is common in this population and responds poorly to PDE5 inhibitors alone. 6

3. Consider PDE5 inhibitors (tadalafil, sildenafil) as first-line ED treatment rather than switching antihypertensives, since these are safe and effective when combined with ACE inhibitors. 1, 5

4. Only if other causes are excluded, consider switching to an ARB (angiotensin receptor blocker), which has similarly low ED risk. 1

Critical Safety Point

The 2017 ACC/AHA guidelines explicitly state that phosphodiesterase-5 inhibitors make drug class distinctions for erectile dysfunction less relevant, since effective ED treatment is now available that can be safely combined with virtually all antihypertensives except nitrates. 1 This means perindopril can be continued for its cardiovascular benefits while ED is treated directly with PDE5 inhibitors if needed.

Bottom Line

The likelihood of perindopril 8 mg daily causing erectile dysfunction is very low to negligible—substantially lower than diuretics or traditional beta-blockers, and comparable to placebo in controlled trials. 1, 2 If ED occurs, it is far more likely attributable to the underlying hypertension, vascular disease, or other comorbidities rather than the perindopril itself. 4, 5