Which Diuretic is Most Likely to Produce Gynecomastia?

Gynecomastia is a well-known extracardiac side effect that can be caused by the use of certain diuretics. Furosemide, an ASA diuretic used to treat congestive heart failure, has been reported to cause gynecomastia. Therefore, the risk of gynecomastia may be increased if these two drugs are taken together. This class of drugs includes spironolactone, eplerone and amiloride. Spironolactone is an aldosterone receptor antagonist that works on the distal tubule and collecting ducts, reducing the reabsorption of sodium and water and decreasing the excretion of potassium.

Its main action is to reduce the expression of epithelial sodium channels (ENAc) and renal external medullary potassium channels (ROMK), resulting in a slow onset and compensation of action. As its main site of action is in the manipulation of sodium and water in the distal tubules and collecting ducts, spironolactone is a relatively weak diuretic. However, it is effective as a blood pressure lowering agent, although it is rarely used as an initial treatment for hypertension. Spironolactone has the advantage over thiazide-like diuretics in that it does not cause hypokalemia or hyperuricemia and does not alter glucose tolerance. However, spironolactone has antiandrogenic activity by binding to the androgen receptor and preventing it from interacting with dihydrotestosterone.

This can lead to nipple tenderness and gynecomastia in some male patients (~ 6%), which depends on the dose and may limit its use. Another concern with potassium-sparing diuretics in general is the risk of hyperkalemia in people with substantially reduced GFR (see analysis below).Asa and thiazide diuretics may cause metabolic alkalosis due to increased excretion of chloride in proportion to bicarbonate. This is more common with ASA diuretics than with thiazide diuretics. They can also cause hypokalemia, hyperglycemia and glucose intolerance, hyperlipidemia, hyponatremia, hyperuricemia, and hypomagnesemia.

Thiazide diuretics may cause hypercalcemia, while ASA diuretics increase calcium excretion, which may result in hypocalcaemia. In addition, asa and thiazide diuretics are sulfonamides and can cause allergic reactions. Asa diuretics also have the potential to cause ototoxicity and hearing loss. It should be noted that hypokalemia can cause ventricular arrhythmias and muscle weakness.