Anti-androgens¶
Anti-androgens reduce the effect of testosterone so that estrogen can drive feminization unopposed. Two mechanisms are in routine use:
- Androgen receptor (AR) antagonists — bind testosterone's receptor without activating it, so circulating T can't reach its target. Spironolactone, cyproterone acetate, bicalutamide, flutamide.
- 5α-reductase inhibitors — block conversion of testosterone to its more potent metabolite DHT (the androgen most responsible for body/facial hair and male-pattern hair loss). Finasteride, dutasteride. Progesterone also inhibits 5α-reductase.
Once estradiol levels are high enough to suppress LH/FSH (typically E2 100–200 pg/mL), the testes produce far less testosterone on their own — and an anti-androgen often becomes a smaller dose or, post-orchiectomy, can be stopped entirely.
Doses are reference, not prescription
Doses below come from the Endocrine Society 2017 guideline and the hemingways.org capture (2002-era provider regimens). Real prescribing depends on your labs, other meds, and provider judgment. Don't titrate without monitoring.
At a glance¶
| Drug | Brand(s) | Mechanism | Route | Typical M2F dose | Notes |
|---|---|---|---|---|---|
| Spironolactone | Aldactone | AR antagonist (+ K-sparing diuretic) | Oral | 100–300 mg/day | First-line in US / informed-consent |
| Cyproterone acetate | Androcur | Strong AR antagonist + weak progestogen | Oral | 12.5–50 mg/day | Common outside US; not FDA-approved |
| Bicalutamide | Casodex | Strong AR antagonist | Oral | 25–50 mg/day | Rising in IC clinics; rare hepatotoxicity |
| Finasteride | Propecia, Proscar | 5α-R inhibitor (Type II) | Oral | 1–5 mg/day | DHT-only; usually for hair, not primary AA |
| Dutasteride | Avodart | 5α-R inhibitor (Type I + II) | Oral | 0.5 mg/day | Stronger DHT block than finasteride |
| Flutamide | Eulexin | Strong AR antagonist | Oral | (largely abandoned) | Hepatotoxicity deaths reported; avoid |
Spironolactone (Aldactone)¶
The default anti-androgen in US informed-consent protocols. Originally a potassium-sparing diuretic and blood-pressure med — its anti-androgen activity was a side effect that turned out to be useful. Cheap, widely available, and well-tolerated by most.
Required monitoring: serum potassium and renal function. Hyperkalemia is the main risk; symptoms (muscle weakness, palpitations) can appear suddenly. Avoid NSAIDs, ACE inhibitors, ARBs, and high-potassium supplements without medical supervision. Also a real diuretic — expect frequent urination and stay hydrated.
Full detail (mechanism, side effects, source notes)
Mechanism: Competes with DHT at peripheral androgen receptors. Also enhances androgen breakdown, increases T→E conversion, and inhibits T production at the 17-hydroxylation step.
Side effects: Confusion, dizziness, drowsiness, headache. GI upset (cramping, diarrhea, dry mouth). Skin: acne, increased body/facial hair (paradoxically, before it works), red patches from capillary congestion. Voice deepening, drug fever, sodium loss. One report of suicidal depression.
Comments from source: Brand-name Aldactone tastes notably worse than the generic (relevant if pills don't go down whole). Do not take sublingually.
Source dose (Lawrence 2002): 100–400 mg/day pre-op, 50 mg/day post-op.
Cyproterone acetate (Androcur)¶
The standard anti-androgen across most of Europe, UK, Canada, and Australia. Not FDA-approved in the US, so US patients rarely encounter it. Stronger AR antagonism than spironolactone with weak progestogenic activity, which contributes additional T suppression via pituitary feedback.
Why doses have come down: older protocols used 50–100 mg/day; modern European practice increasingly uses 10–25 mg/day after a large French cohort study (Weill et al., BMJ 2021) demonstrated a strong dose-dependent link to intracranial meningioma. The ENIGI follow-up later showed that 10–12.5 mg/day suppresses testosterone as effectively as 25–50 mg/day with no measurable difference in feminization or symptom burden — so there is no clinical trade-off in dropping to the low end of the range.
Meningioma risk is dose- and duration-dependent
The Weill 2021 cohort (253,777 women, ~10,800 of them trans) found:
- HR 6.6 for cumulative exposure ≥ 3 g in the first 6 months
- HR 11.3 for cumulative exposure 36–60 g
- HR 21.7 for cumulative exposure ≥ 60 g
Absolute incidence rose from ~4.5 to ~23.8 per 100,000 person-years. The background rate is low, so even a 20× hazard ratio is a small absolute risk — but it is not zero, and the cumulative-dose thresholds are reachable on standard trans-feminine regimens:
| Daily dose | Cumulative exposure per year | Time to reach 60 g |
|---|---|---|
| 50 mg/day | 18.25 g | ~3.3 years |
| 25 mg/day | 9.1 g | ~6.6 years |
| 12.5 mg/day | 4.6 g | ~13 years |
| 10 mg/day | 3.65 g | ~16 years |
Risk falls substantially after discontinuation (HR 1.8 one year after stopping). Meningiomas associated with CPA are typically benign and slow, but case reports in trans women include giant tumors requiring craniotomy, so symptoms (new persistent headache, vision changes, seizures, focal neurological signs) warrant prompt MRI rather than a wait-and-see.
Practical implication: if you are on CPA, target the lowest dose that keeps T suppressed (typically 10–12.5 mg/day once estradiol is in range), and discuss baseline + periodic MRI with your provider if you have been on higher doses for years. Post-orchiectomy, stop CPA — there is no residual benefit and the risk continues to accrue with exposure.
Full detail (mechanism, contraindications, source notes)
Mechanism: Androgen receptor antagonist. Weak inhibition of gonadal androgen production. Has weak progesterone-like activity at the AR and pituitary.
Contraindications: liver disease or tumor, history of blood clots, severe chronic depression, severe diabetes with vascular complications, sickle-cell anemia, Dubin-Johnson or Rotor syndromes (bilirubin metabolism disorders), wasting diseases.
Side effects: Headache, reduced concentration, depression, fatigue, nausea, blood-clotting changes, liver dysfunction or tumors, shortness of breath. Carbohydrate metabolism shifts (worth tracking glucose).
Comments from source: "Some people find 10 mg/week sufficient to induce total impotence; others take as much as 200 mg/day with no obvious short-term adverse effects." Start conservative and titrate up. Doses over 100 mg/day generally considered excessive. Don't confuse with the antibiotic Cipro.
Source dose: 10 mg/week to 100 mg/day pre-op, not recommended post-op.
Bicalutamide (Casodex)¶
A non-steroidal AR antagonist originally developed for prostate cancer. Increasingly used in informed-consent clinics as an alternative to spironolactone — particularly for patients who can't tolerate spiro's diuretic effects or hyperkalemia risk. Not in the Endocrine Society 2017 guideline; its use in feminizing HRT is established by clinical practice rather than formal guideline.
The risk to know: rare but serious hepatotoxicity (~1% in trials, deaths reported post-marketing, typically in the first 3–4 months). LFTs at baseline and periodically thereafter are the standard precaution. Hot flashes are common (~50% of users in oncology trials).
Full detail (mechanism, side effects, source notes)
Mechanism: Competitively binds cytosol androgen receptors in target tissues. As monotherapy in prostate cancer trials, serum testosterone and estradiol rise (the body responds to androgen blockade by producing more T) — relevant for feminizing HRT, where adequate estrogen is what suppresses pituitary feedback and brings T down.
Delivery: 50 mg tablets. (The hemingways source has a copy-paste error stating "0.5 mg dutasteride per soft gelatin capsule" — that's the dutasteride spec. Casodex is 50 mg tablets.)
Side effects: Hot flashes (~50%), dry mouth, nausea, edema, decreased libido, fatigue, hepatotoxicity (rare but serious), gynecomastia and breast pain (in cis male prostate-cancer patients — note that in feminizing HRT this is desired effect from estrogen, not the AA).
Source notes: "Three times less potent as an anti-androgen than the equivalent dose of flutamide." But its safety profile is much better than flutamide's, which is why it's the modern choice when a stronger AA than spiro is wanted.
Finasteride (Propecia, Proscar)¶
Not a general anti-androgen — it only blocks 5α-reductase Type II, the enzyme that converts T to DHT. Useful for slowing or partially reversing male-pattern hair loss and reducing body hair, but does nothing for circulating testosterone. Most often used as an adjunct to a primary AA, not as a stand-alone.
Full detail (mechanism, dosing, source notes)
Mechanism: Inhibits Type II 5α-reductase, blocking T→DHT conversion in the prostate, scalp, and skin. Type I (predominantly in skin and liver) is unaffected — for that, dutasteride.
Delivery: 5 mg tablets (Proscar) or 1 mg tablets (Propecia). Propecia is just a smaller-dose Proscar.
Comments from source: Anecdotal: pill fragments taken daily appear as effective as taking the whole pill. Avoid handling the powder if you might be pregnant — finasteride is a strong teratogen (causes genital deformity in male fetuses). Effects on male fertility appear reversible within 6 weeks of stopping (rabbit/rat data).
Side effects: Generally mild and transient. Some users report persistent sexual dysfunction or mood changes ("post-finasteride syndrome") — debated in the literature, but worth knowing about.
Source dose: 0.05–1 mg/day pre- and post-op.
Dutasteride (Avodart)¶
A more aggressive 5α-reductase inhibitor that blocks both Type I and Type II isoforms — including the Type I activity in skin and liver that finasteride misses. Reduces serum DHT by ~85–90% within two weeks of starting.
Full detail (mechanism, side effects, source notes)
Mechanism: Competitive inhibitor of both Type 1 and Type 2 5α-reductase. Does not bind the androgen receptor. Median DHT reduction: 85% at 1 week, 90% at 2 weeks. Median serum testosterone rises ~19% (within physiologic range).
Side effects: Decreased libido, erectile/ejaculatory dysfunction, breast tenderness or swelling. Reduced ejaculate volume in some patients (without functional impairment).
Cautions: Easily absorbed through skin — pregnant or potentially-pregnant people should not handle the capsules. Men taking dutasteride should not donate blood for at least 6 months after stopping (risk to a pregnant transfusion recipient). Caution if also taking strong CYP3A4 inhibitors (e.g. ritonavir).
Source notes: "Effectiveness has not been tested when used in conjunction with other common HRT medications." Source's pre/post-op doses (2.5–5 mg/day pre, 0.5 mg/day post) are flagged as "guesswork — there is little, if any, experience with this drug in TS patients." Standard is 0.5 mg/day per the manufacturer label.
Flutamide (Eulexin) — generally avoided¶
Strong AR antagonist used historically in feminizing HRT, now largely abandoned because of hepatotoxicity: between Feb 1989 and Dec 1994 the FDA logged 20 deaths and 26 hospitalizations from liver failure, roughly 3 per 10,000 users. Bicalutamide does the same job with a much better safety profile. Listed here for completeness; not recommended.
Progesterone — also a 5α-reductase inhibitor¶
Natural micronized progesterone blocks 5α-reductase as effectively as finasteride in some studies (97% in one trial; results vary widely). It also has independent effects on bone, mood, breast tissue development, and sleep — covered in detail on the Progestogens page.
Sources¶
- Hembree WC et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons. Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869–3903. doi:10.1210/jc.2017-01658
- Per-drug pharmacology, side-effect lists, and historical doses adapted from the hemingways.org GIDinfo drug pages.
- Lawrence A. Suggested Hormone Regimens. (2002 reference handout, archived PDF) — for historical comparison.
- Weill A et al. Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study. BMJ. 2021;372:n37. PubMed — primary source for the dose-response hazard ratios cited in the meningioma callout (HR 6.6 / 11.3 / 21.7 by cumulative exposure tier; HR 1.8 one year post-discontinuation).
- Nota NM et al. A systematic review and meta-analysis of the association between cyproterone acetate and intracranial meningiomas. Sci Rep. 2022. Nature
- Development and Growth of Intracranial Meningiomas in Transgender Women Taking Cyproterone Acetate as Gender-Affirming Progestogen Therapy: A Systematic Review. Transgender Health. 2023. PMC — case-level evidence in trans-feminine cohorts specifically.
- ENIGI dose-reduction substudy (Belgian Endocrine Society 2023 abstract). Endocrine Abstracts — equivalent T suppression at 10–12.5 mg/day vs 25–50 mg/day.