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Spironolactone is a potassium-sparing diuretic that has hormonal effects due to its action as an aldosterone antagonist. One notable adverse effect associated with spironolactone is gynecomastia, which is the abnormal enlargement of breast tissue in males. This side effect occurs more frequently with spironolactone compared to eplerenone due to spironolactone having a higher affinity for steroid receptors, leading to estrogenic effects.

Eplerenone, while also an aldosterone antagonist, is designed to be more selective, which results in a lower incidence of hormone-related side effects, including gynecomastia. Therefore, the risk of developing gynecomastia is significantly greater with spironolactone therapy. This distinction is crucial for clinicians when considering the side effect profiles of these medications in the management of heart failure.

Other adverse effects listed, like bradycardia, hyperkalemia, and prolonged QT interval, can occur with both medications, but they do not have the same significant difference in frequency between spironolactone and eplerenone as gynecomastia does. Therefore, understanding the hormonal activity of spironolactone is essential in recognizing why gynecom