ACE Inhibitors and ARBs Have Equivalent Male-Specific Side Effect Profiles
Based on the available evidence, there is no specific ACE inhibitor or ARB that demonstrates fewer male-specific side effects, as the literature focuses predominantly on female adverse reactions rather than male sexual health outcomes. The systematic reviews examining sex-specific adverse drug reactions in cardiovascular medications do not report sexual dysfunction or other male-specific side effects as primary outcomes 1.
Key Evidence Gaps
The most comprehensive systematic review of sex-specific adverse drug reactions to guideline-recommended heart failure drugs found that only 7% of studies (11 out of 155) reported sex-specific adverse reaction data 1. Critically, none of these studies specifically evaluated male sexual dysfunction, erectile dysfunction, or other male-specific side effects 1.
Documented Sex-Specific Adverse Reactions
The available evidence shows:
- ACE inhibitors: Women experience 2.5 times more cough than men and higher rates of angioedema (5.16 vs 2.32 per 1,000 person-years) 1
- ARBs: No significant sex differences in kidney impairment, hyperkalemia, or hypotension were found in the HEAAL study with losartan 1
- General tolerability: Men had higher discontinuation rates with spironolactone (28% vs 16% in women) due to gynecomastia, but this was for mineralocorticoid receptor antagonists, not ACE inhibitors or ARBs 1
Clinical Decision-Making in the Absence of Male-Specific Data
ARBs May Offer Practical Advantages
In the absence of specific data on male sexual side effects, ARBs represent a reasonable first choice based on overall tolerability profiles 1. A large population-based study of 19,698 patients found that women showed better persistence with ARBs than ACE inhibitors, likely due to fewer adverse reactions 1. While this study focused on women, the lower overall adverse reaction burden suggests ARBs may be better tolerated generally.
Specific Considerations
- Cough avoidance: ARBs produce significantly less cough than ACE inhibitors across both sexes, which may improve overall medication adherence 1, 2
- Angioedema risk: ARBs appear to have lower rates of angioedema compared to ACE inhibitors, though this remains a class effect concern 2
- Equivalent efficacy: The ONTARGET study demonstrated that ARBs are equivalent to ACE inhibitors for cardiovascular mortality and morbidity in secondary prevention 3
Practical Recommendation Algorithm
For male patients concerned about medication side effects:
Start with an ARB (losartan, valsartan, candesartan, or telmisartan) as first-line therapy due to better overall tolerability profile 1, 2
Monitor for class-effect adverse reactions common to both ACE inhibitors and ARBs:
If ARB is ineffective or not tolerated, switch to an ACE inhibitor rather than combining therapies, as combination ACE inhibitor + ARB therapy increases adverse events without additional cardiovascular benefit in most patients 3
Avoid combination ACE inhibitor + ARB therapy except in specific heart failure populations with incomplete neuroendocrine blockade, as ONTARGET showed increased adverse events without benefit 3
Critical Caveat
The absence of male-specific sexual health data in cardiovascular medication trials represents a significant evidence gap 1. Neither ACE inhibitors nor ARBs have been systematically studied for effects on erectile function, libido, or other male sexual health parameters in large-scale trials. Any clinical decisions regarding these concerns must be based on individual patient response rather than comparative evidence between agents.
The 2017 ACC/AHA Hypertension Guidelines explicitly state there is no evidence that choice of antihypertensive medication differs between sexes, but this reflects the lack of sex-specific outcome data rather than proven equivalence 1.