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Spironolactone Gynaecomastia and Eplerenone — EECC MCQ

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EasyCardiac PharmacologySpironolactone Gynaecomastia and EplerenoneEECC

A 45-year-old man with hypertension develops gynaecomastia and breast tenderness 3 months after starting spironolactone 50 mg for resistant hypertension. What is the mechanism and alternative?

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Correct answer: B — Spironolactone has anti-androgenic effects (blocks androgen receptors and inhibits testosterone synthesis), causing gynaecomastia in 10-20% of men; eplerenone is a selective MRA without anti-androgenic properties and is the recommended alternative

Spironolactone is a non-selective MRA that also binds androgen and progesterone receptors. Anti-androgenic effects cause: gynaecomastia (10-20% of men, dose-dependent), breast tenderness, erectile dysfunction, and menstrual irregularities in women. Eplerenone is a selective MRA (>100-fold greater selectivity for the mineralocorticoid receptor over androgen/progesterone receptors) and does NOT cause anti-androgenic side effects. The 2024 ESC Hypertension Guidelines recommend: (1) spironolactone as the preferred fourth-line antihypertensive (PATHWAY-2 trial — most effective fourth agent for resistant HTN); (2) switch to eplerenone if anti-androgenic side effects develop; (3) eplerenone is also the preferred MRA in HFrEF post-MI (EPHESUS trial). Gynaecomastia typically resolves within weeks to months after stopping spironolactone.

Reference: ESC (2024): Hypertension Guidelines; PATHWAY-2 Trial