Spironolactone (Aldactone)

Spironolactone has two faces and you need to know both. First it is an aldosterone antagonist: it blocks the mineralocorticoid receptor in the kidney, so less sodium is retained and less potassium is excreted. Hence the name potassium-sparing diuretic.

Second it is an anti-androgen, because it additionally blocks the androgen receptor and inhibits testosterone synthesis. That is not a side effect in the sense of an accident, it is a genuine second pharmacological action of the same substance. For men that is the decisive point.

This information is for research and educational purposes only. No medical advice.

Aldosterone acts in the collecting duct of the kidney through a receptor in the cell nucleus that first has to drive production of transport proteins. That is exactly why spironolactone works slowly: the full effect takes two to four weeks. As rapid water loss before an event it is the wrong tool, furosemide is built for that.

For blood pressure, on the other hand, it is the strongest fourth agent there is. The reason: a large share of resistant hypertension has an excessive aldosterone level behind it, and no other agent attacks that directly.

The anti-androgen effect is small at low dose and rises clearly with dose. At 25mg it is rarely noticeable, from 100mg it is common.

RALES (NEJM 1999) is the classic. Over 1,600 patients with severe heart failure received an additional 25mg spironolactone or placebo. The trial was stopped early: 30 percent lower mortality. The dose was deliberately low, this was not about diuresis but about receptor blockade.

PATHWAY-2 (Lancet 2015) answered the question of which fourth agent works best in resistant hypertension. Spironolactone clearly beat both bisoprolol and doxazosin. That is why it is standard at this position today.

TOPCAT (NEJM 2014) belongs here for honesty: in heart failure with preserved ejection fraction, spironolactone missed its primary endpoint. Later analysis found strong regional differences, with a clear effect in North and South America and none in Eastern Europe, which raised doubts about trial conduct there. The benefit in preserved ejection fraction is still not considered proven.

SAFA (BMJ 2023) documented the dermatological use: in women with acne, spironolactone significantly improved skin findings versus placebo.

• Raised potassium: the most dangerous side effect, because it can hit the heart without warning signs. Combined with ACE inhibitors or sartans it must be tracked with bloodwork.
• Gynecomastia in men: dose-dependent, rare at 25mg, common from 100mg. Usually recedes after stopping, but not always completely.
• Loss of libido and erectile problems: same cause, same dose dependence.
• Cycle irregularities in women: common at the dermatological dose.
• Kidney values: need checking with longer use.

Store dry, at room temperature and protected from light. Keep out of reach of children.