Bicalutamide

抗雄激素 C

比卡鲁胺

Bicalutamide

Oral

Bicalutamide is a potent non-steroidal androgen receptor (AR) antagonist originally developed for prostate cancer treatment. In transgender HRT, it is considered a last-resort antiandrogen — to be considered only when CPA, spironolactone, and GnRH agonists are all unavailable. WPATH SOC 8 explicitly does not recommend it for routine GAHT.

Off-Label Use

The use of bicalutamide in transgender women’s HRT constitutes off-label use ^[1] :

• WPATH SOC 8 explicitly notes that bicalutamide carries rare but potentially fatal hepatotoxicity that cannot be fully prevented through monitoring
• No drug labeling lists gender-affirming hormone therapy as an approved indication
• The Endocrine Society 2017 guidelines do not discuss bicalutamide
• Current data from transgender populations derives from small observational studies (approximately 170 cases combined)

Contraindicated in Combination with CPA

Bicalutamide and CPA (cyproterone acetate) must never be used simultaneously.

Both carry hepatotoxic potential; combined use may result in additive liver injury risk. This contraindication is grounded in pharmacological safety principles — no study has directly evaluated the safety of co-administration, but given the individual hepatotoxicity profiles of each drug, no responsible clinical practice should permit their concurrent use.

If switching from CPA to bicalutamide (or vice versa), the first drug must be discontinued under medical supervision, with a gap of at least 2–4 weeks and confirmed normal liver function before initiating the second drug.

Pharmacology

Mechanism of Action

Bicalutamide is among the non-steroidal AR antagonists with the highest binding affinity currently in clinical use:

1. Potent AR blockade (sole mechanism): Competitively blocks androgen receptors, preventing testosterone (T) and DHT from exerting biological effects
2. Does not lower testosterone levels: Due to feedback mechanisms, T levels may actually rise
3. No effect on the GnRH–LH/FSH axis: Does not suppress the hypothalamic–pituitary–gonadal axis

Pharmacokinetics

• Oral bioavailability: Approximately 90%
• Steady-state half-life: 5–6 days — meaning a missed dose has minimal impact on plasma concentration, though frequent missed doses should still be avoided
• Time to peak concentration: Approximately 31 hours
• Time to steady state: Approximately 4 weeks

The Problem of Rising Testosterone Levels

This is a distinctive phenomenon when bicalutamide is used in GAHT ^[1] :

• Once bicalutamide blocks AR, the hypothalamus no longer senses androgen-mediated negative feedback
• The pituitary compensates by increasing LH secretion, stimulating the testes to produce more testosterone
• Serum testosterone levels may rise to 1.5–2× pre-treatment values
• While the biological effects of T are blocked, elevated T can be converted to estradiol via aromatase
• In prostate cancer patients, this testosterone rise sometimes leads to gynecomastia

Implications for transgender users: Although AR is blocked, elevated testosterone levels mean that if the drug is stopped or adherence drops, masculinizing effects may return rapidly.

Dosage Recommendations

Protocol	Dose	Notes	Source
Starting / Standard	25 mg/day	Low dose used in the majority of transgender studies to date	Angus 2024; Burgener 2025
Adjustment Range	25–50 mg/day	Titrated based on clinical response	Neyman 2019 (50 mg); Angus 2024 (25 mg)
Absolute Maximum	50 mg/day	Higher doses provide no additional benefit but increase hepatotoxicity risk	FDA label (prostate cancer combination therapy dose)

Do Not Use Testosterone Levels to Assess Efficacy

When using bicalutamide, serum testosterone cannot serve as a marker of treatment response. Testosterone levels may remain normal or even rise; as long as AR is effectively blocked, androgenic effects are suppressed ^[2] . Efficacy should be assessed on clinical signs (reduced sebum production, slower body hair growth, etc.) rather than testosterone values alone.

Adverse Effects

Hepatotoxicity (Most Important Risk)

Hepatotoxicity is the primary reason limiting bicalutamide’s use in GAHT ^[1] :

FDA label data (from prostate cancer clinical trials):

• Approximately 6% experienced transient asymptomatic ALT elevation
• Approximately 1% discontinued due to hepatitis or significant enzyme elevation
• Large 150 mg monotherapy trial (EPC, n=8,113): abnormal LFTs in 3.4% (vs. 1.9% placebo)
• At least 10 serious liver injury case reports have been published post-marketing, including 2 fatalities

Transgender population data (limited but informative):

• Neyman 2019: 23 adolescents, 50 mg/day, no clinically significant hepatotoxicity ^[2]
• Fuqua 2024: 40 adolescents in follow-up, 50 mg/day, no serious hepatic events ^[3]
• Angus 2024: 24 adults, 25 mg/day, 1 case of mild enzyme elevation (reversible) ^[4]
• Wilde 2024: 1 case report, 50 mg/day, hepatotoxicity developed (reversible upon discontinuation) ^[5]

These datasets remain too small in aggregate (approximately 170 cases) to rule out rare but serious hepatic injury.

Symptoms of Liver Injury — Stop Immediately and Seek Medical Care

• Yellowing of the skin or whites of the eyes (jaundice)
• Dark urine (tea-colored)
• Persistent pain or discomfort in the upper right abdomen
• Unusual fatigue, loss of appetite, nausea, or vomiting
• ALT/AST > 3× the upper limit of normal

If any of the above symptoms appear, discontinue bicalutamide immediately and seek medical evaluation of liver function.

Pulmonary Toxicity (Interstitial Lung Disease)

The FDA label includes a post-marketing warning for interstitial lung disease (ILD), including interstitial pneumonitis and pulmonary fibrosis, some of which have been fatal.

• Overall incidence is extremely low: approximately 0.01% (1/10,000), far lower than the related drug nilutamide (0.77%)
• Japanese pharmacovigilance data: Matsumoto 2020 analyzed the Japanese Adverse Drug Event Report database (JADER) and found a reporting odds ratio for bicalutamide-associated ILD of 9.2 (95% CI 7.9–10.6), with a median onset time of 50 days ^[6]

Note on Pulmonary Toxicity Risk in Asian Populations

Japanese pharmacovigilance databases show a higher number of bicalutamide-related ILD reports, but this does not indicate a genetic predisposition in Asian individuals — Japan’s overall reporting rate for drug-induced ILD is higher than other countries (likely reflecting reporting culture and prescribing patterns). No prospective study has demonstrated racial differences in risk. Nevertheless, if dry cough, dyspnea, or fever develops, seek medical attention promptly and inform the treating clinician of bicalutamide use.

Breast Pain and Gynecomastia

• Bicalutamide commonly causes gynecomastia in prostate cancer patients
• In transgender users, this effect may be considered a desired outcome
• Breast tenderness is relatively common

Other Adverse Effects

• Hot flashes (less frequent than with GnRH agonists)
• Gastrointestinal discomfort (nausea, diarrhea)
• Dry skin

Monitoring Requirements

Test	Frequency	Target / Alert Threshold	Action
Liver function (ALT/AST)	Baseline + monthly for the first 6 months → then every 3 months	ALT/AST ≤ upper limit of normal	>3× ULN: discontinue immediately and seek medical evaluation
Bilirubin	Concurrent with liver function tests	Normal range	Elevation indicates worsening hepatic injury
Testosterone (T)	Every 3–6 months	For reference only (T may be elevated)	Not a primary marker of treatment efficacy
Estradiol (E2)	Concurrent with testosterone	100–200 pg/mL	Assess effectiveness of the combined regimen

Liver Function Monitoring Is Non-Negotiable

Even if you feel completely well, monthly liver function testing for the first 6 months of bicalutamide use cannot be omitted. Liver injury may be asymptomatic and can only be detected early through blood testing. If you are unable to commit to monthly liver function monitoring, bicalutamide should not be used.

Appropriate Use Cases

Bicalutamide has a very limited role in GAHT ^[1] :

Consider only when all of the following conditions are met:

• CPA is unavailable (not marketed locally / intolerance / meningioma risk)
• Spironolactone is unavailable (renal impairment / hyperkalemia risk / insufficient effect)
• GnRH agonists are unavailable (financial / access barriers)
• Medical supervision and regular monitoring are in place

Contraindications:

• Pre-existing liver disease or abnormal liver function
• Currently using CPA or other hepatotoxic medications
• Unable to undergo regular liver function blood tests

Availability

• Regulatory status: Bicalutamide is approved in mainland China (for prostate cancer treatment)
• Access: Can be prescribed through urology or oncology departments
• Brands: Casodex (originator) and domestic generics (e.g., Langyi)
• Cost: Originator approximately CNY 200–400/month; generics approximately CNY 50–150/month (50 mg tablets)
• Note: Most physicians are unfamiliar with its application in GAHT; obtaining a prescription may require framing the indication around prostate-related conditions

品牌图鉴

🇬🇧英国

康士得 Casodex

厂商

阿斯利康 (AstraZeneca)

规格

50mg × 28片

外观

白色薄膜衣片

原研比卡鲁胺，价格较高

🇮🇳印度

Calutide

厂商

Cipla

规格

50mg

外观

白色薄膜衣片

Cipla 仿制比卡鲁胺，价格为原研的 1/5-1/10

🇮🇳印度

Bicalox

厂商

多种印度厂商

规格

50mg

外观

白色薄膜衣片

印度仿制比卡鲁胺

🇮🇳印度

Bicatero

厂商

Hetero

规格

50mg

外观

白色薄膜衣片

Hetero 集团生产，全球仿制药大厂

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