From the Guidelines
Eplerenone is significantly less likely to cause gynecomastia compared to spironolactone, with a incidence rate of less than 1% in patients taking eplerenone, as supported by the most recent study in 2023 1.
Key Points
- Eplerenone has a more selective binding profile compared to spironolactone, resulting in minimal interaction with androgen and progesterone receptors.
- This selective binding profile leads to a significantly lower incidence of gynecomastia in patients taking eplerenone, as shown in a study published in 2023, where gynecomastia occurred in 1.3% of patients taking eplerenone, compared to 9.1% of those on spironolactone 1.
- The typical dosage of eplerenone ranges from 25-50mg daily, and it should be taken consistently for optimal therapeutic effect.
- Patients should be aware that while the risk is lower, gynecomastia remains a possible, though rare, side effect with eplerenone.
Comparison with Spironolactone
- Spironolactone commonly causes gynecomastia due to its binding to androgen receptors and anti-androgenic effects.
- Eplerenone, on the other hand, has a more selective binding profile, making it a preferred option for male patients who need a mineralocorticoid receptor antagonist but are concerned about gynecomastia, as noted in a study published in 2019 1.
Clinical Implications
- The lower incidence of gynecomastia with eplerenone makes it a preferred option for male patients who need a mineralocorticoid receptor antagonist.
- Patients should be monitored for signs of gynecomastia, and the dosage of eplerenone should be adjusted accordingly.
- The benefits of eplerenone in reducing the risk of gynecomastia should be weighed against its potential effects on morbidity, mortality, and quality of life, as noted in a study published in 2007 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.
- Gynecomastia is a reported adverse reaction associated with eplerenone therapy, as indicated in the clinical trials experience section of the drug label 2.
- The occurrence of gynecomastia increased with the duration of eplerenone therapy.
- It is a known side effect of eplerenone.
From the Research
Eplerenone and Gynecomastia
- Eplerenone is a selective aldosterone receptor antagonist that has been shown to have a lower incidence of gynecomastia compared to spironolactone 3, 4, 5, 6, 7.
- The American College of Cardiology recommends trying spironolactone first and then switching to eplerenone if patients develop gynecomastia, menstrual irregularities, or impotence 3.
- A study found that eplerenone reversed spironolactone-induced painful gynaecomastia in cirrhotic patients, with all 19 patients expressing alleviation of pain 6.
- A systematic review and meta-analysis found that eplerenone exhibited a reduced risk of gynecomastia (RR = 0.07,95% CI [0.02 to 0.31], P = 0.0001) compared to spironolactone 7.
Comparison with Spironolactone
- Eplerenone has been shown to have a similar antihypertensive efficacy to spironolactone, but with a lower risk of gynecomastia and other hormonal side effects 3, 4, 5, 7.
- The EPHESUS study found that eplerenone significantly reduced mortality and cardiovascular morbidity in post-myocardial infarction patients with systolic heart failure, but did not compare eplerenone directly with spironolactone 5.
- A systematic review and meta-analysis found that eplerenone showed a lower risk of all-cause mortality (HR = 0.78,95%CI [0.64 to 0.94], P = 0.009) and cardiovascular mortality (HR = 0.54,95%CI [0.39,0.74], P = 0.0001) compared to spironolactone 7.