Can Irbesartan (Angiotensin II Receptor Antagonist) or Hydrochlorothiazide (HCTZ) (Diuretic) affect libido?

Can Irbesartan or HCTZ Affect Libido?

HCTZ can negatively affect libido and erectile function, particularly at higher doses, while irbesartan (an ARB) does not impair sexual function and may actually improve it.

HCTZ and Sexual Dysfunction

Thiazide diuretics like HCTZ are associated with increased sexual dysfunction, especially at higher doses. 1

• The JNC 7 guidelines specifically note that "some reports have described an increased degree of sexual dysfunction when thiazide diuretics, particularly at high doses, are used" 1
• In the Treatment of Mild Hypertension Study (TOMHS), participants randomized to chlorthalidone (a thiazide-like diuretic similar to HCTZ) reported a significantly higher incidence of erection problems through 24 months, though this effect diminished by 48 months to levels similar to placebo 1
• The sexual dysfunction risk is dose-dependent: higher doses (>50 mg/day HCTZ or >25 mg chlorthalidone) are more strongly associated with adverse effects 1
• However, the VA Cooperative study found no significant difference in sexual dysfunction occurrence between diuretics and other antihypertensive medications 1
• Short-term exposure studies (6-14 weeks) showed HCTZ was associated with self-reported impotence at no greater prevalence than placebo 2

Important caveat: The evidence shows conflicting results depending on study duration and dose, with short-term studies showing minimal effect while longer-term studies at higher doses show increased dysfunction 1, 2

Irbesartan and Sexual Function

Irbesartan (an ARB) does not impair sexual function and may actually improve it. 3, 4, 5

• The 2017 ACC/AHA guidelines note that "beta blockers, mineralocorticoid receptor antagonists, and other antihypertensive drugs can have negative effects on libido and erectile function," but ACE inhibitors and ARBs are not included in this list 1
• A large observational study of 1,069 hypertensive patients with metabolic syndrome showed that irbesartan treatment significantly improved erectile function (P<0.0001), with ED prevalence declining from 78.5% to 63.7% after 6 months 4
• This improvement occurred regardless of whether irbesartan was used alone or combined with HCTZ 4
• In women, the felodipine-irbesartan combination improved sexual function scores (desire, arousal, orgasm) compared to felodipine-metoprolol, likely through reduced oxidative stress 5
• Animal studies in rats showed losartan (another ARB) preserved sexual function better than propranolol, with only minimal effects on libido after 90 days at high doses 6

Clinical Implications

When prescribing for patients concerned about sexual function:

• ARBs like irbesartan are preferred over beta-blockers and thiazide diuretics for patients with sexual dysfunction concerns 3
• If a patient develops sexual dysfunction on HCTZ, consider switching to an ARB-based regimen before adding ED-specific treatment 3
• The combination of irbesartan/HCTZ appears to maintain the beneficial effects of irbesartan on sexual function despite the presence of HCTZ 4
• Do not assume all sexual dysfunction is medication-related: hypertension itself causes endothelial dysfunction that contributes to ED independent of treatment 1, 3

Common Pitfalls to Avoid

• Don't overlook that up to 40% of hypertensive men experience ED, often under-reported due to embarrassment 3
• Don't fail to recognize ED as a cardiovascular risk marker that may precede other cardiovascular disease manifestations 1, 3
• Don't use high-dose thiazides unnecessarily: doses >50 mg/day HCTZ add little antihypertensive benefit but increase adverse effects including sexual dysfunction 1