Spironolactone in Gender-Affirming Care

Spironolactone (Aldactone) is a diuretic used off-label as an anti-androgen in feminizing hormone therapy. It is widely used, particularly 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 that blocks the action of the adrenal hormone aldosterone in the kidneys.

Anti-androgenic action

Its anti-androgenic action is a secondary effect. Spironolactone blocks androgen receptors in peripheral tissues and inhibits enzymes involved in testosterone production. As a result, exposure to endogenous testosterone decreases, which is desirable in feminizing hormone therapy.

Use in transition

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

Side effects and risks

Known side effects include hyperkalemia (elevated blood potassium levels), polyuria (frequent urination), thirst, postural hypotension, and fatigue. The risk of hyperkalemia is greater in people with reduced kidney function or those taking ACE inhibitors or potassium supplements at the same time. Periodic monitoring of potassium levels and kidney function is recommended. The risks associated with the other medications are described under side effects of hormone therapy.

Status in the Netherlands

In Dutch gender-affirming care, spironolactone is prescribed less often than cyproterone acetate. After an orchiectomy, an anti-androgen is generally no longer needed. Amsterdam UMC and UMCG follow protocols in which cyproterone acetate is the standard anti-androgen for adults, and GnRH agonists are used for adolescents. Spironolactone may be an alternative when cyproterone acetate is not tolerated. For hair loss, finasteride is sometimes used as an adjunct to feminizing hormone therapy. The Amsterdam UMC protocol is described on genderzorgnederland.nl.