Spironolactone
Overview
Spironolactone ("spiro") is a potassium-sparing diuretic that also acts as a weak androgen receptor blocker. It is the most commonly prescribed anti-androgen for trans women in the United States.
| Property | Details |
|---|---|
| Drug class | Potassium-sparing diuretic; androgen receptor antagonist |
| Mechanism | Competitively blocks androgen receptors; reduces testosterone production (mild) |
| Half-life | 1.4 hours (metabolites longer) |
| Typical dose | 50–200 mg/day |
| Frequency | Once or twice daily |
How It Works
Spironolactone works through two mechanisms:
- Androgen receptor blockade — competes with testosterone for androgen receptor binding sites
- Mild T suppression — reduces testosterone production by a small amount (much less than CPA or GnRH agonists)
It also has anti-mineralocorticoid effects (hence its use as a diuretic for heart failure and high blood pressure).
Note on efficacy: Recent studies (2024-2025) found that when combined with injectable E2, spironolactone did not provide statistically significant additional T suppression compared to E2 alone. One study found spironolactone was associated with lower serum E2 levels. However, spironolactone still blocks androgen receptors at the tissue level, which may contribute to feminisation even when T is already suppressed by E2. These findings primarily apply to injectable E2 users.
Dosing
| Level | Dose | Frequency |
|---|---|---|
| Starting | 25–50 mg/day | Once daily |
| Typical | 100 mg/day | 50 mg twice daily |
| Maximum | 200 mg/day | 100 mg twice daily |
Start low, go slow
Starting at 25–50 mg/day and increasing gradually helps minimise side effects like dizziness, frequent urination, and electrolyte imbalances.
Side Effects
| Side Effect | Frequency | Notes |
|---|---|---|
| Frequent urination | Very common | It's a diuretic — expected |
| Dizziness/low blood pressure | Common | Take with food; stay hydrated |
| Salt cravings | Very common | The body loses sodium |
| Breast tenderness | Common | Can enhance estrogen's breast effects |
| Dehydration | Common | Ensure adequate fluid and salt intake |
| Hyperkalemia (high potassium) | Uncommon but serious | Risk increases with age; monitor potassium |
| Stomach upset | Occasional | Take with food |
| Menstrual-like cramps | Some report | Temporary |
| Reduced libido | Common | Anti-androgen effect |
Hyperkalemia (High Potassium)
Spironolactone can raise potassium levels. This is rarely clinically significant in healthy people under 45, but risk increases with:
- Age over 45
- Kidney disease
- Taking NSAIDs (ibuprofen, naproxen), ACE inhibitors, or other potassium-raising meds
- Eating a very high-potassium diet
Monitoring: Check potassium 2–4 weeks after starting, then every 3 months in year 1, then annually. Note: the Warnock et al. (2022) study suggests routine monitoring may be unnecessary in those under 45 without risk factors, but the Endocrine Society's official guidelines still recommend 3-monthly monitoring for all patients. This is emerging evidence challenging current protocol.
NSAIDs and Spironolactone
Avoid high‑dose or frequent use of ibuprofen, naproxen, or other NSAIDs while on spironolactone. These drugs can raise your potassium to dangerous levels when combined with spiro.
Occasional low‑dose use (e.g., one 200 mg ibuprofen) is unlikely to harm, but paracetamol (acetaminophen) is a safer alternative for routine pain relief.
Drug Interactions
| Medication | Interaction |
|---|---|
| NSAIDs (ibuprofen, naproxen) | Can worsen kidney function and raise potassium |
| ACE inhibitors (lisinopril, etc.) | Risk of hyperkalemia |
| Other diuretics | Excessive electrolyte loss |
| Lithium | Spiro can raise lithium levels |
| Digoxin | Spiro can raise digoxin levels |
| Potassium supplements | Do NOT take potassium supplements with spiro |
Comparison to Other Anti-Androgens
| Aspect | Spironolactone | Bicalutamide | CPA |
|---|---|---|---|
| Effectiveness | Moderate | Moderate | High |
| Side effect burden | High (diuretic effects) | Low | Moderate |
| Hyperkalemia risk | Yes | No | No |
| Meningioma risk | No | No | Yes |
| Cost | Low | Moderate | Low |
| Availability | Widely prescribed | Less common | Common (non-US) |
Who Should Avoid Spironolactone
- People with kidney disease
- People with Addison's disease
- People on ACE inhibitors or ARBs (unless carefully monitored)
- People with low blood pressure (baseline)
- People who can't tolerate frequent urination
References
Warnock JK, et al. (2022). The utility of monitoring potassium in transgender, gender diverse, and nonbinary individuals on spironolactone. Oxford Academic. https://scholarworks.indianapolis.iu.edu/items/cd3646fe-ea49-416d-a289-6c7381f1c5bd
Hembree WC, et al. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons. JCEM. https://academic.oup.com/jcem/article/102/11/3869/4157558
UCSF Transgender Care. Anti-androgens. https://transcare.ucsf.edu/guidelines