From the Guidelines
Eplerenone is less likely to cause gynecomastia compared to spironolactone when used for heart failure treatment. While both medications are mineralocorticoid receptor antagonists used to manage heart failure, eplerenone was specifically developed to have a more selective binding profile. According to a recent study published in 2023 1, gynecomastia is observed with spironolactone and not eplerenone, making this AE easily avoidable for those who may be concerned. The study found that just over half of all noted episodes of gynecomastia could be attributed to MRA use, but on average, only 0.9% more patients experienced this in the intervention arm as compared to the placebo arm of MRA trials.
Key Points
- Eplerenone has a more selective binding profile compared to spironolactone, resulting in significantly lower rates of gynecomastia (less than 1%) 1.
- Spironolactone has a well-documented side effect of gynecomastia (breast tissue enlargement in males) occurring in approximately 10% of male patients because it binds to androgen and progesterone receptors in addition to mineralocorticoid receptors.
- The typical dosing for eplerenone in heart failure is 25-50 mg once daily, with appropriate monitoring of potassium levels and kidney function, as hyperkalemia remains a potential side effect of both medications 1.
- Eplerenone is a preferred option for male patients with heart failure who experienced or are concerned about gynecomastia, due to its lower risk of this side effect compared to spironolactone 1.
Recommendations
- Use eplerenone instead of spironolactone in male patients with heart failure who are concerned about gynecomastia.
- Monitor potassium levels and kidney function regularly in patients taking eplerenone, as hyperkalemia remains a potential side effect.
- Consider the benefits of eplerenone in reducing mortality and hospitalization risk in patients with heart failure, as demonstrated in recent studies 1.
From the FDA Drug Label
Gynecomastia and abnormal vaginal bleeding were reported with eplerenone but not with placebo. The rates increased with increasing duration of therapy.
Eplerenone can cause gynecomastia in patients with heart failure, as it has been reported in clinical trials, particularly with increasing duration of therapy 2.
From the Research
Eplerenone and Gynecomastia in Heart Failure Patients
- Eplerenone is a selective aldosterone receptor antagonist used to treat heart failure and hypertension 3, 4, 5.
- Unlike spironolactone, a non-selective aldosterone receptor antagonist, eplerenone has minimal effects on other steroid receptors, reducing the risk of sex hormone-related adverse effects such as gynecomastia 3, 5.
- Studies have shown that eplerenone is associated with a lower risk of gynecomastia compared to spironolactone in patients with heart failure 4, 6, 5, 7.
- The incidence of gynecomastia in patients taking eplerenone is less than 1% 4.
- A systematic review and meta-analysis found that eplerenone had a significantly lower risk of gynecomastia (RR = 0.07,95% CI [0.02 to 0.31], P = 0.0001) compared to spironolactone 6.
Comparison with Spironolactone
- Spironolactone is a non-selective aldosterone receptor antagonist that can cause gynecomastia and other sex hormone-related adverse effects due to its binding to other steroid receptors 3, 5.
- Eplerenone has been shown to have a more favorable side effect profile compared to spironolactone, with a lower risk of gynecomastia and other sex hormone-related adverse effects 4, 6, 5.
- However, one study found that eplerenone and spironolactone had similar impacts on cardiovascular outcomes and safety in patients with acute decompensated heart failure, although eplerenone was associated with a lower risk of gynecomastia 7.