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Spironolactone in gender care

Spironolactone (Aldactone) is a diuretic used off-label as an anti-androgen in feminising hormone therapy. It is widely used especially in the United States; in the Netherlands cyproterone acetate is more common.

Original indication

Spironolactone was developed as a potassium-sparing diuretic and has been prescribed since the 1960s for hypertension, heart failure and ascites. It is an aldosterone receptor antagonist and blocks the action of the adrenal cortex hormone aldosterone in the kidneys.

Anti-androgenic action

The anti-androgenic action is a secondary effect. Spironolactone blocks androgen receptors in peripheral tissues and inhibits enzymes involved in the production of testosterone. This reduces exposure to endogenous testosterone, which is desired in feminising hormone therapy.

Use in transition

The Endocrine Society Clinical Practice Guideline (2017) names spironolactone as one of the recommended anti-androgens in trans women, alongside GnRH agonists and cyproterone acetate, among others. The WPATH Standards of Care version 8 (2022) confirms this place. The choice between agents is partly determined by regional practice, availability, costs and side effect profile.

Side effects and risks

Known side effects include hyperkalaemia (elevated potassium level in the blood), polyuria (frequent urination), thirst, postural hypotension and fatigue. The risk of hyperkalaemia is greater with reduced kidney function or with concurrent use of ACE inhibitors or potassium supplementation. Periodic monitoring of potassium and kidney function is recommended.

Status in the Netherlands

In Dutch gender care, spironolactone is prescribed less often than cyproterone acetate. Amsterdam UMC and UMCG follow protocols in which cyproterone acetate is the standard anti-androgen in adults, and GnRH agonists in adolescents. Spironolactone can be an alternative when cyproterone acetate is not tolerated.