In a male patient concerned about preserving sexual function, which antihypertensive class or medication is least likely to cause erectile dysfunction?

Antihypertensives Least Likely to Cause Erectile Dysfunction

ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers are the antihypertensive classes least likely to cause erectile dysfunction, with ARBs potentially even improving sexual function. 1, 2

Preferred Antihypertensive Classes for Preserving Sexual Function

First-Line Choices (Neutral or Beneficial Effects)

• Angiotensin Receptor Blockers (ARBs) are the most favorable option, as they have been associated with neutral or even beneficial effects on erectile function 1, 2, 3
• ARBs like irbesartan and valsartan have demonstrated improvement in sexual activity and erectile function in hypertensive men with metabolic syndrome 2, 4
• ACE inhibitors have not been observed to increase the incidence of erectile dysfunction and may be preferred alternatives 1, 2, 5
• Calcium channel blockers have neutral effects on erectile function and do not increase ED incidence 1, 5, 6

Special Consideration: Nebivolol

• Among beta-blockers, nebivolol (which has direct vasodilating properties) is significantly less likely to cause erectile dysfunction compared to traditional beta-blockers 1, 6
• If a beta-blocker is clinically necessary, nebivolol should be the preferred agent 1, 6

Antihypertensives to Avoid in Men Concerned About Sexual Function

High-Risk Medications

• Thiazide diuretics (particularly at doses >50 mg/day HCTZ or >25 mg chlorthalidone) are associated with significantly higher incidence of erectile dysfunction 1, 2, 6
• Traditional beta-blockers (excluding nebivolol) have well-documented negative effects on libido and erectile function 1, 3, 6
• Mineralocorticoid receptor antagonists can have negative effects on erectile function 1, 2
• Centrally acting sympatholytic agents (clonidine, α-methyldopa) have well-documented negative impacts on sexual function 5, 6

Important Nuance on Thiazides

• The TOMHS study showed chlorthalidone significantly increased erection problems at 24 months, though this effect diminished by 48 months 1, 2
• The effect is dose-dependent, with higher doses being more problematic 2
• More recent evidence suggests the negative impact may be less severe than previously thought, but they remain less favorable than ARBs or ACE inhibitors 6

Clinical Management Algorithm

When Starting Antihypertensive Therapy

1. Assess baseline sexual function before initiating treatment, as hypertension itself causes endothelial dysfunction contributing to ED independent of medication 1, 7, 2
2. Choose ARBs, ACE inhibitors, or calcium channel blockers as first-line agents in sexually active men 1, 2
3. Avoid thiazide diuretics and traditional beta-blockers unless compelling indications exist 2, 6

When ED Develops After Starting Treatment

1. Switch the offending agent before adding ED-specific treatment 1, 7, 2
2. Replace beta-blockers or thiazides with ARBs or ACE inhibitors 1, 2
3. Consider PDE5 inhibitors (sildenafil, tadalafil, vardenafil) if switching medications is insufficient or not feasible, as they can be safely coadministered with antihypertensives (except nitrates) 1, 7

Critical Caveats

• Hypertension itself causes ED through endothelial dysfunction, so do not assume all sexual dysfunction is medication-related 1, 7, 2
• Up to 40% of hypertensive men experience ED, often under-reported due to embarrassment 7, 2
• ED may be an early cardiovascular risk marker that precedes other manifestations of cardiovascular disease, warranting comprehensive risk assessment 1, 7
• The VA Cooperative trial found no difference in sexual dysfunction between CCBs, ACE inhibitors, hydrochlorothiazide, or beta-blockers compared to placebo, suggesting individual variation exists 1
• Lifestyle modifications (physical activity, weight loss, smoking cessation) reduce ED risk independent of blood pressure control and should always be encouraged 1, 7