Does the addition of indapamide (a diuretic) 2.5mg to perindopril (an angiotensin-converting enzyme inhibitor (ACE inhibitor)) 8mg daily increase the risk of erectile dysfunction (ED) in a male patient with hypertension and possible benign prostatic hyperplasia (BPH)?

Does Adding Indapamide 2.5mg to Perindopril Increase Erectile Dysfunction Risk?

No, adding indapamide 2.5mg to perindopril does not significantly increase the risk of erectile dysfunction beyond what thiazide-like diuretics already contribute, and this combination may actually be preferable to other antihypertensive regimens in men concerned about sexual function.

Understanding the ED Risk Profile

ACE Inhibitors and Sexual Function

• Perindopril (ACE inhibitor) is not associated with erectile dysfunction and may actually have neutral or potentially beneficial effects on sexual function compared to other antihypertensive classes 1.
• ACE inhibitors do not appear in the list of antihypertensive medications commonly causing ED, unlike beta-blockers and thiazide diuretics 2, 1.

Thiazide-Like Diuretics and ED Risk

• Thiazide-type diuretics are among the antihypertensive drug classes most prominently associated with erectile dysfunction, along with aldosterone receptor blockers and beta-adrenergic receptor blockers 1.
• Indapamide is a thiazide-like diuretic, so the ED risk in the perindopril/indapamide combination comes primarily from the indapamide component, not from adding it to perindopril 1.
• The 2.5mg dose of indapamide is a standard therapeutic dose used in major cardiovascular outcome trials 2, 3.

Clinical Context: Hypertension with Possible BPH

Alpha-Blockers as Alternative Consideration

• For men with both hypertension and BPH, alpha-1 blockers (doxazosin, prazosin, terazosin) may be considered as second-line agents since they treat both conditions and are not associated with increased ED 2.
• Doxazosin specifically has not been associated with increased ED incidence and may improve urinary flow in BPH patients 4, 5, 6.
• However, alpha-blockers are associated with orthostatic hypotension, especially in older adults, and should not be assumed to constitute optimal hypertension management alone 2.

Important Caveat About Alpha-Blockers

• In men with hypertension and cardiac risk factors, doxazosin monotherapy was associated with higher incidence of congestive heart failure compared to other antihypertensive agents 2.
• Patients with hypertension may require separate management of their hypertension beyond alpha-blocker therapy for BPH symptoms 2.

Practical Management Algorithm

If ED is Already Present or a Major Concern:

1. Continue the perindopril/indapamide combination as it provides proven cardiovascular benefit 2, 3.
2. Add phosphodiesterase-5 inhibitors (PDE5i) such as tadalafil or sildenafil, which can be safely coadministered with antihypertensive medications and effectively treat ED 2, 7.
3. The only absolute contraindication to PDE5i is concurrent use of organic nitrates in patients with coronary artery disease 1.

If BPH Symptoms are Prominent:

1. Consider adding an alpha-blocker (doxazosin, tamsulosin, terazosin, or alfuzosin) to address urinary symptoms 2.
2. Tamsulosin has lower probability of orthostatic hypotension but higher probability of ejaculatory dysfunction compared to other alpha-blockers 2.
3. For prostatic enlargement without significant bother, 5-alpha reductase inhibitors (finasteride, dutasteride) are options but cause sexual dysfunction (decreased libido, ejaculatory dysfunction, ED) in some patients 2.

If Blood Pressure Remains Uncontrolled:

1. Add a dihydropyridine calcium channel blocker (amlodipine 5-10mg) to create the preferred three-drug combination of ACE inhibitor + diuretic + CCB 3.
2. This triple therapy achieves BP control rates exceeding 80% and provides superior cardiovascular risk reduction 3.

Key Clinical Pearls

• The "Hawthorne effect" matters: Patient knowledge that a drug may cause ED can increase the reported incidence of ED 1.
• Screen for ED before initiating antihypertensive therapy, as ED is associated with hypertension, coronary artery disease, heart failure, and diabetes independent of treatment 1.
• ED itself may be a precursor to cardiovascular disease due to shared endothelial dysfunction, making it a marker for increased cardiovascular risk 2.
• Beta-blockers and thiazide diuretics cause ED more frequently than ACE inhibitors, ARBs, or calcium channel blockers 1, 4.