From the Guidelines
Eplerenone is less likely to cause gynecomastia compared to spironolactone, with a significantly lower incidence rate of less than 1% in patients taking eplerenone, as opposed to 10-15% with spironolactone, as supported by the most recent study in 2023 1.
Key Points
- Eplerenone has a more selective binding profile, targeting mineralocorticoid receptors with minimal activity at other steroid receptors, resulting in lower rates of gynecomastia.
- Spironolactone, on the other hand, binds to androgen and progesterone receptors, creating hormonal effects that lead to gynecomastia in a significant proportion of male patients.
- The difference in gynecomastia incidence between eplerenone and spironolactone is substantial, making eplerenone a preferred option for male patients concerned about this side effect.
- Clinical studies, including the most recent one in 2023 1, demonstrate the lower risk of gynecomastia with eplerenone, supporting its use as a safer alternative to spironolactone in terms of this specific side effect.
Recommendations
- For male patients requiring a potassium-sparing diuretic who are concerned about gynecomastia, eplerenone should be considered as the first-line treatment option due to its lower risk of causing this side effect.
- If a patient develops gynecomastia while taking spironolactone, switching to eplerenone may resolve the issue while maintaining therapeutic benefits, as suggested by the evidence 2, 1.
- Monitoring of serum potassium levels is crucial when initiating eplerenone treatment, and adjustments should be made according to the patient's response and side effect profile, as outlined in the guidelines 3.
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 4.
- 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 5, 6, 7, 8, 9.
- The American College of Cardiology recommends trying spironolactone first and then switching to eplerenone if patients develop gynecomastia, menstrual irregularities, or impotence 5.
- A study found that eplerenone reversed spironolactone-induced painful gynaecomastia in cirrhotic patients, with all 19 patients expressing alleviation of pain 8.
- 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 9.
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 5, 6, 7, 9.
- 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 7.
- 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 9.