Is Eplerenone (generic) available and is male sexual dysfunction caused by Spironolactone (Aldactone) permanent?

Eplerenone Generic Availability and Spironolactone Sexual Side Effects

Yes, eplerenone is available as a generic medication, and the sexual dysfunction caused by spironolactone is reversible upon discontinuation—it is not permanent. 1, 2

Eplerenone Generic Status

• Eplerenone is widely available in generic formulations and is listed in major clinical guidelines as a standard treatment option for resistant hypertension and heart failure. 1
• The medication is prescribed at typical doses of 50-100 mg daily, often requiring twice-daily dosing for adequate blood pressure control. 1, 2

Spironolactone Sexual Side Effects: Reversibility

The sexual dysfunction and gynecomastia caused by spironolactone are NOT permanent and resolve after discontinuation. 2, 3

Mechanism of Sexual Side Effects

• Spironolactone causes gynecomastia, impotence, and decreased libido through cross-inhibition of androgen and progesterone receptors—this is a pharmacologic effect, not permanent tissue damage. 1
• These hormone-related adverse effects occur because spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors. 3
• In the landmark RALES trial, 10% of patients on spironolactone developed painful gynecomastia. 2

Clinical Evidence for Reversibility

• The side effects are dose-dependent and pharmacologically mediated, meaning they reverse when the drug is stopped or the dose is reduced. 4, 3
• Spironolactone has been used for nearly 2 decades, and the sexual side effects are well-characterized as reversible upon discontinuation. 5

Why Eplerenone is Preferred for Male Patients

Eplerenone was specifically engineered with a 9,11-epoxide group to achieve selective mineralocorticoid receptor binding while avoiding the sexual side effects of spironolactone. 1, 2

Comparative Side Effect Profiles

• Eplerenone has minimal affinity for progesterone and androgen receptors, resulting in significantly lower rates of gynecomastia and sexual dysfunction compared to spironolactone. 1, 2
• In a direct comparison study, 21.2% of men on spironolactone developed gynecomastia versus only 4.5% on eplerenone (P=0.033). 6
• Male patients particularly benefit from eplerenone due to the minimal risk of gynecomastia and sexual dysfunction. 2

Clinical Guidelines Recommendation

• Both the American College of Cardiology and American Heart Association recommend eplerenone and spironolactone as preferred agents for resistant hypertension and primary aldosteronism. 1
• Guidelines explicitly note that spironolactone is associated with greater risk of gynecomastia and impotence compared with eplerenone. 1

Important Caveats

Potency Differences

• Spironolactone is more potent than eplerenone for blood pressure reduction—in patients with primary aldosteronism, spironolactone reduced DBP by 12.5 mmHg versus 5.6 mmHg with eplerenone (P<0.001). 6
• Eplerenone has a shorter half-life and requires twice-daily dosing in many patients for adequate blood pressure control. 1

Hyperkalemia Risk

• Both medications carry similar risks of hyperkalemia and require identical monitoring protocols: check potassium and creatinine at baseline, 2-3 days, 7 days, monthly for 3 months, then every 3 months. 2
• Discontinue potassium supplements when initiating either agent. 2
• Both are contraindicated if baseline potassium >5.0 mEq/L or eGFR <30 mL/min/1.73m². 2

Male Fertility Considerations

• The FDA label notes that eplerenone may compromise male fertility based on animal data showing decreased fertility at 17 times the therapeutic dose, though reversibility was not evaluated. 7
• This is distinct from the reversible sexual dysfunction caused by spironolactone's androgen receptor blockade. 7

Clinical Decision Algorithm

For male patients requiring mineralocorticoid receptor antagonist therapy:

1. First-line: Eplerenone 50-100 mg daily (may require twice-daily dosing) to avoid sexual side effects. 1, 2

2. Alternative: Spironolactone 25-100 mg daily if cost is prohibitive or greater potency is needed, with counseling that sexual side effects are reversible upon discontinuation. 1, 2

3. Monitor potassium at baseline, 2-3 days, 7 days, monthly × 3, then every 3 months regardless of agent chosen. 2