Aldosterone Antagonists in the Treatment of Heart Failure

Todd R. Marcy; Toni L. Ripley


Am J Health Syst Pharm. 2006;63(1):49-58. 

In This Article

Adverse Endocrinologic Effects

Additional adverse effects of spironolactone result from its anti-androgenic and antiprogestational activities. Spironolactone antagonizes androgen receptors,[44] reduces 17α-reductase activity,[88] and lowers plasma levels of testosterone and androstenedione, causing gynecomastia, mastodynia, loss of libido, impotence, and menstrual abnormalities. In RALES, gynecomastia or mastodynia occurred in 10% of men receiving spironolactone and in only 1% of men taking placebo (p < 0.001).[4] Mastodynia occurred in 2% and 0.1% of men receiving spironolactone and placebo, respectively.

Gynecomastia was also reported in a retrospective study of hypertensive patients (n = 699) taking spironolactone for at least two months.[89] Gynecomastia occurred in 88 patients enrolled in the study and was dose dependent, with 52.2% of those receiving at least 150 mg of spironolactone daily for a mean of 23 months developing gynecomastia; 6.9% of men taking 50 mg or less of spironolactone daily developed gynecomastia. Onset of gynecomastia occurred at any point of spironolactone therapy, and the mean time to the adverse effect was dose dependent. For patients taking spironolactone 150 mg or more daily, the average time to gynecomastia onset was 9 months, compared with 27 months in those receiving 50 mg or less of the drug daily. No cumulative dose association was found. Gynecomastia was resolved in 86 of the 88 patients when spironolactone treatment was discontinued or the dose was decreased.

Eplerenone was developed as a selective aldosterone antagonist in order to avoid the endocrinologic effects observed with spironolactone. EPHESUS found similar rates of gynecomastia, impotence, and breast pain in the eplerenone-treated and placebo groups.[5] The only adverse effects more common in the treatment group were a 2.2% absolute increase in gastrointestinal disorders (p = 0.02) and the aforementioned increased rate of hyperkalemia.