Which is better, CPA or spironolactone?

Both are first-line options endorsed by WPATH SOC 8; there is no universal winner. CPA gives more reliable T suppression but carries cumulative risks of meningioma and hepatotoxicity; spironolactone is easier to obtain and has no meningioma risk, but requires close potassium monitoring. The choice depends on individual comorbidities, monitoring conditions, and access.

What should I watch for when switching from CPA to spironolactone?

During the switch, first titrate spironolactone up to target dose for 2-4 weeks, then taper CPA off gradually to avoid testosterone rebound. Within the switching window, check potassium, renal function, and testosterone every 2-4 weeks. See our antiandrogen switching guide for detailed steps.

Can CPA and spironolactone be used together?

Routine combination is not recommended. Side effects stack (hepatotoxicity + hyperkalemia) and there is no additional T-suppression benefit. In special cases (monotherapy fails to suppress T) short-term combination may be used under medical supervision with intensified monitoring.

When should CPA be avoided?

History of meningioma or abnormal baseline MRI, severe hepatic impairment, cumulative dose approaching 10 g, and young users planning long-term HRT (>5 years) should preferentially consider spironolactone or a GnRH agonist.

When should spironolactone be avoided?

Renal insufficiency (eGFR <30), history of hyperkalemia, severe hypotension, or concurrent ACEI/ARB use without potassium monitoring capability. If feminization results are unsatisfactory and there are no CPA contraindications, CPA may be the better choice.

CPA vs Spironolactone: Clinical Comparison of Antiandrogen Choice

CPA (cyproterone acetate, commonly sold as Androcur) and spironolactone (Aldactone) are the two most widely used antiandrogens in MTF HRT in the Chinese-speaking world. This page compares them dimension by dimension along clinical decision axes. It does not give a universal recommendation — the choice should be made by a clinician based on individual comorbidities, monitoring conditions, and drug availability.

If your situation is →	Recommended choice
You want serum T to drop quickly into the female range	CPA 5-12.5 mg · more reliable negative-feedback suppression
Existing depressive tendency / abnormal liver function / planning long-term use (>5 years)	Spironolactone · no cumulative meningioma risk
Concurrent ACEI/ARB use or high-potassium diet	CPA · spironolactone’s potassium-sparing effect compounds hyperkalemia risk
Renal insufficiency (eGFR <60)	CPA (reduced dose) · spironolactone contraindicated
Easy access in mainland China / cost-conscious	Spironolactone · widely available domestic generics, covered by insurance
History of meningioma / abnormal baseline MRI	Spironolactone · CPA absolutely contraindicated
Pregnancy / breastfeeding / under 18	Neither recommended; please see a clinician

Not sure? Read on for the detailed comparison, or use the risk self-screener for help.

At a Glance

Dimension	CPA (Androcur)	Spironolactone (Aldactone)
Mechanism	Progesterone receptor agonism + weak AR antagonism + LH/FSH suppression	Aldosterone antagonism (potassium-sparing diuretic) + high-dose AR antagonism
T-suppression efficacy	More reliable (negative feedback at the pituitary)	Moderate (mostly receptor blockade; serum T may not reach castrate range)
Standard dose	5-12.5 mg/day	100-300 mg/day
Evidence level	A	A
Most serious long-term risk	Meningioma (cumulative-dose related)	Hyperkalemia (renal-function related)
Monitoring focus	Liver function · prolactin · cumulative dose · headache/visual changes	Potassium · renal function · blood pressure
Availability in mainland China	Prescription-only; obtainable at psychiatry/endocrinology clinics	Stocked in cardiology/nephrology departments; relatively easy to obtain
Monthly cost	~30-80 RMB	~10-30 RMB

Mechanistic Differences

CPA: multi-pathway suppression, primarily negative feedback

CPA reduces androgen action through three mechanisms^[15]:

Progesterone-receptor negative feedback (primary): suppresses hypothalamic GnRH → reduced pituitary LH/FSH → decreased testosterone synthesis
Weak androgen-receptor antagonism: far weaker than bicalutamide, limited clinical relevance
Mild 5α-reductase inhibition: reduces T → DHT conversion

Result: serum testosterone usually drops to the female range (<50 ng/dL); effect is more stable when combined with estrogen.

Spironolactone: dual-pathway aldosterone + androgen

Spironolactone is originally a potassium-sparing diuretic; its antiandrogen action comes from competitive androgen-receptor blockade at high doses^[7]^[23]:

Aldosterone-receptor antagonism (primary mechanism): potassium-sparing diuresis, lowers blood pressure
Androgen-receptor antagonism (high dose): emerges above 100 mg
Mild suppression of testosterone synthesis: mechanism not fully understood

Result: serum testosterone may only drop moderately or remain in the normal range, but tissue-level androgen action is blocked, and clinical feminization is still achievable.

T-Suppression Efficacy

Indicator	CPA 5-12.5 mg	Spironolactone 100-300 mg
Median serum testosterone reduction	80-95%	30-60%
Proportion reaching female range (<50 ng/dL)	Higher	Lower; usually requires E2 co-administration
Onset time	4-8 weeks	6-12 weeks
Effect on DHT	Moderate	Indirectly reduced via AR blockade

Key point: for users who are “serum-number sensitive” (wanting T values in the female range), CPA reaches target more easily; for “symptom-oriented” users (focused on body hair, sebum, libido), both can be effective.

Side-Effect Profile

Main risks of CPA

Other risks:

Hepatotoxicity: ALT/AST elevation, rare acute liver failure; check liver function every 3-6 months
Low mood / depression: progestogenic effect, reported by ~10-20% of users
Hyperprolactinemia: monitor PRL; persistent elevation suggests dose reduction
Decreased libido: expected effect of marked T suppression; some users find it bothersome

Main risks of spironolactone

Other risks:

Polyuria / nocturia: diuretic effect; most tolerate within 4-8 weeks
Hypotension / orthostatic dizziness: prominent during initiation
Breast tenderness: common, usually does not require discontinuation
Libido fluctuation: significant individual variation

Contraindications

Contraindication	CPA	Spironolactone
History of meningioma	Absolute contraindication	Safe
Severe hepatic impairment	Contraindicated	Use with caution
Renal insufficiency (eGFR <30)	Reduce dose	Contraindicated
Known hyperkalemia	Safe	Contraindicated
Concurrent ACEI/ARB without monitoring	Safe	Contraindicated
Active depressive/bipolar episode	Use with caution	Relatively safe
Pregnancy (in fertile users)	Contraindicated	Contraindicated

Monitoring Schedule

Time point	CPA	Spironolactone
Baseline	Liver function · prolactin · MRI (optional)	Potassium · renal function · blood pressure
Week 2	—	Potassium · blood pressure
Week 6-8	Testosterone · liver function · prolactin	Testosterone · potassium · renal function
Every 3-6 months	Liver function · prolactin · cumulative-dose review	Potassium · renal function
Annually	Brain MRI (long-term users)	Breast screening

Availability in Mainland China

CPA: “Sepukon” (Androcur) 50 mg is the main strip; some hospitals stock domestic “cyproterone acetate tablets”. Psychiatry, endocrinology, and reproductive medicine departments can prescribe. ~30-80 RMB per box; insurance coverage limited
Spironolactone: “Aldactone” 20 mg/40 mg dominate; stocked in cardiology, nephrology, and dermatology (acne indication). Cheap, widely covered by insurance

Black market / overseas mail order: not recommended due to counterfeiting, uncontrolled storage temperatures, and lack of traceability.

How to Choose (Clinical Decision Framework)

Prefer CPA when:

You want serum T values in the female range
Spironolactone monotherapy fails to suppress T sufficiently
You have renal issues or tendency toward elevated potassium
You cannot tolerate the diuretic effects of spironolactone

Prefer spironolactone when:

You are a young user planning long-term HRT (>5 years) where cumulative dose matters
You have a history of meningioma or abnormal baseline MRI
You also need blood-pressure control or cardiovascular protection
CPA is unavailable or financially burdensome

Consider GnRH agonist when:

Both CPA and spironolactone are contraindicated/intolerable
You need maximal T suppression (transitional period before gonadectomy)
Finances permit

E2 injection monotherapy / high-dose monotherapy:

Some users achieve natural T suppression on high-dose E2 injection and can stop antiandrogens
Must be done under clinician supervision with continuous blood monitoring

Switching Workflow

See the detailed guide: Complete Antiandrogen Switching Guide