In a hypertensive male with new‑onset erectile dysfunction, which antihypertensive drugs are most likely to cause it and how should the medication regimen be modified?

Antihypertensive Drugs Causing Erectile Dysfunction

Beta-blockers (excluding nebivolol), thiazide diuretics at higher doses, and mineralocorticoid receptor antagonists are the primary antihypertensive agents that cause erectile dysfunction, and you should switch to an ARB, ACE inhibitor, or calcium channel blocker before adding PDE5 inhibitor therapy. 1, 2

Antihypertensive Agents Most Likely to Cause Erectile Dysfunction

High-Risk Medications

• Traditional beta-blockers (excluding nebivolol) have well-documented negative effects on both libido and erectile function and should be avoided in sexually active men. 1, 2, 3
• Thiazide diuretics at doses exceeding 50 mg/day hydrochlorothiazide or 25 mg/day chlorthalidone are strongly associated with erectile dysfunction, with reported rates of approximately 17% versus 8% in placebo over two years. 1, 2
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) adversely affect erectile function and should be replaced when possible. 1, 2
• Centrally acting sympatholytics (clonidine, methyldopa) have a well-documented negative impact on sexual function, though controlled trial data are limited. 4, 5

Neutral or Beneficial Medications

• Angiotensin receptor blockers (ARBs) are associated with neutral or even beneficial effects on erectile function and represent the most favorable antihypertensive class for preserving sexual health. 2, 4
• ACE inhibitors have not been shown to increase erectile dysfunction incidence and are safe alternatives for men concerned about sexual function. 1, 2, 4
• Calcium channel blockers demonstrate neutral effects on erectile function and do not raise the risk of erectile dysfunction. 1, 2, 4
• Nebivolol (a vasodilating beta-blocker) is significantly less likely to cause erectile dysfunction compared with traditional beta-blockers and should be the preferred beta-blocker when one is clinically required. 2, 3

Medication Regimen Modification Algorithm

Step 1: Identify the Offending Agent

• Review the patient's current antihypertensive regimen and identify any high-risk medications (traditional beta-blockers, high-dose thiazides, mineralocorticoid receptor antagonists). 1, 2
• Assess the temporal relationship between medication initiation and onset of erectile dysfunction symptoms. 2

Step 2: Switch Before Adding ED-Specific Treatment

• Replace beta-blockers or thiazide diuretics with an ARB or ACE inhibitor as the first intervention when erectile dysfunction is attributed to the original agent. 1, 2
• If a beta-blocker is absolutely necessary for cardiac indications (post-MI, heart failure), switch to nebivolol specifically. 2, 3
• For patients requiring diuretic therapy, consider switching to a lower dose thiazide or using an alternative diuretic class. 2

Step 3: Add PDE5 Inhibitor Therapy if Medication Switch Insufficient

• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are first-line therapy for erectile dysfunction in patients with controlled hypertension and can be safely coadministered with antihypertensive medications. 6, 1
• These agents have additive blood pressure-lowering effects (typically modest), which is generally well-tolerated and may even provide cardiovascular benefit. 1
• Absolute contraindication: Never prescribe PDE5 inhibitors to patients taking nitrates in any form (sublingual, oral, transdermal, or recreational "poppers") due to risk of severe, potentially fatal hypotension. 1, 7

Step 4: Titrate PDE5 Inhibitor Dosing

• Provide instructions to maximize benefit and efficacy when prescribing oral PDE5 inhibitors. 6
• Titrate the dose to provide optimal efficacy, as dose-response effects are well-established. 6
• Sildenafil, tadalafil, vardenafil, and avanafil have similar efficacy in the general erectile dysfunction population. 6

Critical Safety Considerations Before Treatment

Cardiac Risk Stratification

• High-risk patients (unstable angina, uncontrolled hypertension, recent MI/stroke within 2 weeks, severe heart failure, high-risk arrhythmias) should not receive ED treatment until cardiac condition stabilizes. 1
• Low-risk patients (controlled hypertension, mild stable angina, uncomplicated past MI, successful revascularization, <3 cardiovascular risk factors) can receive all first-line therapies. 1
• Intermediate-risk patients require cardiology evaluation before initiating ED therapy. 1

Common Pitfalls to Avoid

Do Not Assume All ED is Medication-Related

• Hypertension itself causes endothelial dysfunction that contributes to erectile dysfunction independent of treatment effects. 1, 2, 3
• Approximately 40% of hypertensive men experience erectile dysfunction, often under-reported due to patient embarrassment. 1, 2
• Erectile dysfunction may serve as an early marker of cardiovascular risk and warrants comprehensive cardiovascular risk assessment. 1, 2

Do Not Overlook Other Contributing Factors

• Evaluate for diabetes, dyslipidemia, obesity, smoking, and other cardiovascular risk factors that share common pathophysiology with erectile dysfunction. 1
• Screen for concomitant medications that cause ED, particularly SSRIs, which cause decreased libido and orgasmic dysfunction. 7
• Address lifestyle factors: encourage physical activity, weight loss, and smoking cessation, as these reduce erectile dysfunction risk independent of blood pressure control. 1, 2

Do Not Fail to Screen Proactively

• Assess baseline sexual function prior to initiating antihypertensive therapy, as hypertension itself can cause endothelial dysfunction leading to erectile dysfunction. 2
• Erectile dysfunction is often under-reported due to patient embarrassment and physician discomfort discussing the topic. 1

Adverse Effects of PDE5 Inhibitors

• The most frequently reported adverse events include dyspepsia, headache, flushing, back pain, nasal congestion, myalgia, visual disturbance, and dizziness. 6
• Average rates are similar across medications with exceptions: dyspepsia (lowest with avanafil), flushing (lowest with tadalafil), and myalgia (lowest with vardenafil and avanafil). 6
• Most adverse events follow a dose-response pattern, with higher doses producing higher rates of side effects. 6