Bicalutamide is an oral, nonsteroidal androgen receptor blocker (antiandrogen). It is sold as Casodex (an AstraZeneca trademark) and as generics, and the FDA first approved it in 1995. It sits on the androgen receptor and stops testosterone and dihydrotestosterone (DHT) from activating it, without being a hormone itself.
Its only FDA-approved use is 50 mg once daily together with a luteinizing hormone-releasing hormone (LHRH) drug for metastatic prostate cancer. The single most important fact for a non-cancer reader: when bicalutamide is taken on its own by a man with working testes, it does not lower testosterone. Testosterone and estradiol rise, and breast enlargement (gynecomastia) becomes very common.
This page summarizes what the FDA label, the major prostate cancer trials and the published pharmacology report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Nonsteroidal androgen receptor inhibitor (antiandrogen) |
| Brand / approval | Casodex (originally AstraZeneca); US approval 1995; generics available |
| Route | Oral tablet |
| Strength | 50 mg |
| Labeled dose | 50 mg once daily, combined with an LHRH analog, for stage D2 metastatic prostate cancer |
| Half-life (label) | 5.8 days for the active R-enantiomer in healthy men (≈ 1 week) |
| Key mechanism fact | Blocks the receptor; on its own it raises testosterone and estradiol rather than lowering them |
| Boxed warning | None; label warnings cover liver failure, bleeding with warfarin-type drugs and gynecomastia |
| US status | Prescription drug; not a controlled substance |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Bicalutamide is a small synthetic molecule, not a steroid. Its chemical name is N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide, with a molecular weight of 430.37 (FDA label). The tablet contains a racemate, a 50:50 mix of two mirror-image forms. Almost all of the antiandrogen activity comes from the R-enantiomer; the S-enantiomer is essentially inactive.
The label describes it as having “no other known endocrine activity.” It competes with testosterone and DHT for the androgen receptor in target tissue. DHT still binds the receptor more tightly than any of the nonsteroidal antiandrogens. Among those drugs, bicalutamide binds two to four times more strongly than 2-hydroxyflutamide (flutamide’s active form) and about twice as strongly as nilutamide in rat and human prostate receptor assays (Kolvenbag et al., Prostate Cancer Prostatic Dis 1998).
Why it raises testosterone when used alone
The brain senses androgens through the same receptor that bicalutamide blocks. With the receptor blocked, the pituitary reads the signal as “too little androgen” and releases more of the gonadotropins, including luteinizing hormone (LH), which drives the testes to make more testosterone. Some of that extra testosterone is converted to estradiol.
- The FDA label notes rises in serum testosterone and estradiol in trials of bicalutamide as a single agent.
- A pharmacokinetic review from the manufacturer reported that daily dosing raises gonadotropins and sex hormones, with testosterone up by as much as 80%, although most patients stayed within the normal range (Cockshott, Clin Pharmacokinet 2004).
- When bicalutamide is combined with an LHRH analog, the LHRH drug still shuts down testosterone production, and bicalutamide does not change that suppression.
This is the reason for the drug’s signature side effect: more estradiol acting on breast tissue whose androgen receptors are blocked.
Pharmacokinetics
Figures below are from the FDA label unless stated otherwise (FDA label):
| Parameter | Value |
|---|---|
| Time to peak, single dose (healthy men, n = 30) | 31.3 h (SD 14.6) |
| Peak concentration, single dose | 0.768 mcg/mL |
| Half-life of active R-enantiomer (healthy men) | 5.8 days (SD 2.29) |
| Steady-state concentration in prostate cancer patients (n = 40) | 8.939 mcg/mL |
| Protein binding | 96% |
| Effect of food | No clinically significant effect |
| Share of steady-state plasma level that is R-enantiomer | About 99% |
Key points:
- Slow build-up. The R-enantiomer is absorbed slowly, has a half-life of about a week and accumulates about 10-fold in plasma with daily dosing (Cockshott 2004).
- Dose plateau. Steady-state levels rise in proportion to dose up to 50 mg, rise less than proportionally above that and plateau above 300 mg.
- Liver clearance. The R-enantiomer is mainly oxidized, probably by CYP3A4, and then glucuronidated; the S-enantiomer is mostly glucuronidated. Metabolites leave in about equal amounts in urine and feces.
- Severe liver disease. In 4 patients with severe hepatic impairment, the half-life rose from 5.9 to 10.4 days (about 76% longer). Kidney function, age and body weight had no meaningful effect.
Because of the long half-life, the label tells men with female partners who could become pregnant to use effective contraception for 130 days after the last dose.
Approved medical use
The US label approves one use: 50 mg once daily, started at the same time as an LHRH analog (such as goserelin or leuprolide), for stage D2 metastatic prostate cancer. This combination is called combined androgen blockade. The LHRH drug removes testicular testosterone, and bicalutamide blocks the receptor against any androgen that remains.
The label states that 150 mg daily is not approved in the US, either alone or with other treatments. Outside the US, 150 mg once daily has been used as monotherapy for localized or locally advanced (non-metastatic) prostate cancer (Cockshott 2004).
Other uses discussed in the research literature, such as hirsutism in women and gender-affirming care, are off-label. The label states that bicalutamide has no indication for women and is contraindicated in pregnancy.
What the research shows
Combined androgen blockade: bicalutamide vs flutamide
The approval trial randomized 813 men with metastatic prostate cancer to bicalutamide 50 mg once daily or flutamide 250 mg three times daily, each with an LHRH analog, in a double-blind design (Schellhammer et al., Urology 1997). Median follow-up was 160 weeks.
| Outcome | Bicalutamide + LHRH | Flutamide + LHRH | Hazard ratio (95% CI) |
|---|---|---|---|
| Median time to progression | 97 weeks | 77 weeks | 0.93 (0.79–1.10) |
| Median survival | 180 weeks | 148 weeks | 0.87 (0.72–1.05) |
| Diarrhea | 12% | 26% | — |
| Withdrawals for diarrhea | 2 patients | 25 patients | — |
| Hematuria (blood in urine) | 12% | 6% | — |
Neither efficacy difference was statistically significant, so the two drugs were judged equivalent for cancer control. Bicalutamide’s advantages were once-daily dosing and much less diarrhea.
150 mg monotherapy in early prostate cancer
The Early Prostate Cancer program combined three double-blind trials in 8,113 men with localized or locally advanced, non-metastatic disease. Men received standard care (surgery, radiotherapy or watchful waiting) plus bicalutamide 150 mg daily or placebo (Iversen et al., BJU Int 2010). At a median 9.7 years:
| Outcome | Result |
|---|---|
| Progression-free survival, all patients | HR 0.85 (95% CI 0.79–0.91), favoring bicalutamide |
| Overall survival, all patients | HR 1.01, no difference |
| Locally advanced disease plus radiotherapy | Overall survival significantly favored bicalutamide (p = 0.031) |
| Localized disease | No meaningful benefit; survival trend favored placebo under watchful waiting (p = 0.054) |
| Breast pain | 73.7% on bicalutamide |
| Gynecomastia | 68.8% on bicalutamide |
The US label adds safety detail from these programs. In a planned subgroup of 1,627 men with localized disease under watchful waiting, 37.7% died on bicalutamide vs 32.9% on placebo (HR 1.16, 95% CI 0.99–1.37). In men with metastatic (M1) disease, a safety board stopped bicalutamide 150 mg monotherapy compared with castration after interim hazard ratios for death of 1.25 and 1.31 in two trials.
150 mg with salvage radiation (RTOG 9601)
In a double-blind trial, 760 men with a rising PSA after prostatectomy received salvage radiation plus either bicalutamide 150 mg daily for 24 months or placebo (Shipley et al., NEJM 2017). Median follow-up was 13 years.
| Outcome at 12 years | Bicalutamide | Placebo |
|---|---|---|
| Overall survival | 76.3% | 71.3% |
| Death from prostate cancer | 5.8% | 13.4% |
| Metastatic disease | 14.5% | 23.0% |
| Gynecomastia | 69.7% | 10.9% |
The hazard ratio for death was 0.77 (95% CI 0.59–0.99). This is the strongest evidence of a survival benefit for bicalutamide added to another treatment, although the 150 mg dose remains unapproved in the US.
Antiandrogen monotherapy vs castration
A Cochrane review pooled 11 randomized trials (3,060 men) comparing nonsteroidal antiandrogen monotherapy with medical or surgical castration for advanced prostate cancer (Kunath et al., Cochrane 2014):
| Outcome | Antiandrogen vs castration (95% CI) |
|---|---|
| Overall survival | HR 1.24 (1.05–1.48), worse with antiandrogen |
| Stopping treatment for adverse events | RR 1.82 (1.13–2.94) |
| Breast pain | RR 22.97 (14.79–35.67) |
| Gynecomastia | RR 8.43 (3.19–22.28) |
| Hot flashes | RR 0.23 (0.19–0.27), fewer with antiandrogen |
| Loss of sexual interest | RR 0.50 (0.30–0.83), one small study |
The trade-off is consistent: antiandrogen monotherapy keeps testosterone levels up, which spares some castration effects but controls advanced cancer less well.
Bone and body composition
Because testosterone and estradiol stay up, bicalutamide alone does not cause the bone loss seen with castration. In a 12-month open-label trial, 52 men with non-metastatic prostate cancer were randomized to leuprolide or bicalutamide 150 mg daily (Smith et al., JCO 2004):
| Measure (12 months) | Leuprolide | Bicalutamide 150 mg |
|---|---|---|
| Lumbar spine bone density | −2.5% | +2.5% |
| Fat mass | +11.1% | +6.4% |
| Lean mass, muscle size, strength | Similar between groups | Similar between groups |
Breast tenderness and enlargement were more common with bicalutamide; fatigue, loss of sexual interest and hot flashes were less common.
Hirsutism in women (off-label)
In a double-blind trial, 70 women with polycystic ovary syndrome (PCOS) and severe hirsutism took an oral contraceptive plus either bicalutamide 50 mg/day or placebo for 12 months (Moretti et al., JCEM 2018). Hair growth scores fell in both groups and fell more with bicalutamide. Total and LDL cholesterol rose in the bicalutamide group. This is a single trial; the US label does not support use in women.
Side effects and risks
Liver injury
Bicalutamide has no boxed warning, but the label’s first warning is hepatitis:
- Postmarketing reports include deaths and hospitalizations from liver failure, generally within the first 3–4 months of treatment.
- In controlled trials, hepatitis or marked liver enzyme rises led to stopping the drug in about 1% of patients.
- The label calls for liver enzymes (transaminases) before starting, at regular intervals for the first four months and periodically afterward. It says to stop the drug if jaundice appears or ALT rises above two times the upper limit of normal.
In the approval trial, “increased liver enzyme test” was reported in 7% on bicalutamide vs 11% on flutamide. A 2024 case report described bicalutamide-induced hepatotoxicity in a transgender adolescent (Wilde et al., J Adolesc Health 2024), showing the risk is not limited to older men with cancer.
Gynecomastia and breast pain
This is the most common problem with bicalutamide used alone:
| Setting | Gynecomastia | Breast pain |
|---|---|---|
| 50 mg + LHRH analog (label trial) | 9% | 6% |
| 150 mg alone (label, prostate cancer trials) | Up to 38% | Up to 39% |
| 150 mg, Early Prostate Cancer program | 68.8% | 73.7% |
| 150 mg + radiation, RTOG 9601 | 69.7% | — |
In a double-blind trial of 114 men on bicalutamide 150 mg, gynecomastia developed in 73% with placebo, 10% with tamoxifen 20 mg/day and 51% with anastrozole 1 mg/day (Boccardo et al., JCO 2005). A 2025 meta-analysis of 9 randomized trials found that tamoxifen cut gynecomastia risk by 82% (RR 0.18, 95% CI 0.08–0.38), breast radiotherapy cut it by 52% (RR 0.48, 95% CI 0.38–0.59), and anastrozole showed no significant benefit (Spagnolo et al., J Endocrinol Invest 2025). See Nolvadex (tamoxifen) and Arimidex (anastrozole).
Other common effects
In the approval trial (bicalutamide 50 mg plus an LHRH analog, n = 401), the most frequent adverse reactions included (FDA label):
| Adverse reaction | Bicalutamide + LHRH | Flutamide + LHRH |
|---|---|---|
| Hot flashes | 53% | 53% |
| General pain | 35% | 31% |
| Asthenia (weakness) | 22% | 21% |
| Constipation | 22% | 17% |
| Nausea | 15% | 14% |
| Peripheral edema | 13% | 10% |
| Hematuria | 12% | 6% |
| Anemia | 11% | 13% |
Hot flashes are mainly a castration effect: in the Cochrane review above, they were far less common with antiandrogen monotherapy than with castration. The label also notes somnolence and, after marketing, photosensitivity.
Interstitial lung disease
Postmarketing reports include interstitial lung disease (lung inflammation and scarring), some fatal, most often at doses above 50 mg. In an analysis of the FDA Adverse Event Reporting System, bicalutamide was associated with lung disease reports with a reporting odds ratio of 8.19 (95% CI 6.01–11.16) (Wu et al., Br J Clin Pharmacol 2023). Spontaneous-report data show a signal, not an incidence rate.
Drug interactions
- Warfarin and other coumarin anticoagulants. Bicalutamide can displace them from protein binding. Postmarketing reports describe large rises in INR days to weeks after starting, with serious bleeding, including inside the skull. The label calls for close INR monitoring.
- CYP3A4 substrates. R-bicalutamide inhibits CYP3A4. With bicalutamide, midazolam peak levels rose 1.5-fold and total exposure 1.9-fold, so the label advises caution with drugs cleared by CYP3A4.
- LHRH analogs. No interaction with goserelin or leuprolide was found.
Fertility and pregnancy
Antiandrogens can cause changes in sperm shape, and in animal studies bicalutamide inhibited sperm production. The long-term effect on human male fertility has not been studied. In rats, exposure during pregnancy feminized male offspring (hypospadias and undescended testes) at exposures similar to the human dose. Bicalutamide is contraindicated in pregnancy, and the label advises contraception for 130 days after the last dose.
Who should not use it
The label contraindicates bicalutamide in:
- people with a hypersensitivity reaction to it (angioedema and hives have been reported);
- women, for whom it has no indication;
- pregnancy.
It advises caution in moderate-to-severe liver impairment and blood-sugar monitoring when it is combined with LHRH agonists, which can reduce glucose tolerance.
Legal status and use outside medicine
In the US, bicalutamide is a prescription-only drug. It is not listed among the Schedule III anabolic steroids in 21 CFR 1308.13. It is also not named on the WADA 2026 Prohibited List, whose S4 hormone-modulator class covers aromatase inhibitors and anti-estrogens rather than androgen receptor blockers.
We found no controlled studies of bicalutamide in people using anabolic steroids. By design, it blocks the same receptor that anabolic-androgenic steroids act through. In men with working testes, the trials above show it raises testosterone and estradiol and causes gynecomastia in most long-term users at 150 mg.
Key takeaways
- A receptor blocker, not a hormone. Bicalutamide competes with testosterone and DHT at the androgen receptor and has no other known hormonal activity.
- Approved only with castration for metastatic prostate cancer. The US label covers 50 mg daily with an LHRH analog; 150 mg is not approved in the US.
- Alone, it raises testosterone and estradiol. Blocking feedback to the brain increases LH and testosterone, which is why breast enlargement occurred in about 69% of men on 150 mg in two large trials.
- Long half-life. The active form has a half-life of about 6 days in healthy men, accumulates about 10-fold and calls for contraception for 130 days after stopping.
- Liver and bleeding risks need monitoring. Fatal liver failure has been reported, mostly in the first 3–4 months, and it can sharply raise INR in people on warfarin.
Sources
- ANI Pharmaceuticals. Casodex (bicalutamide) tablet, prescribing information, revised September 2025. DailyMed.
- Cockshott ID. Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855–878. PubMed.
- Kolvenbag GJ, Furr BJ, Blackledge GR. Receptor affinity and potency of non-steroidal antiandrogens: translation of preclinical findings into clinical activity. Prostate Cancer Prostatic Dis. 1998;1(6):307–314. PubMed.
- Schellhammer PF, Sharifi R, Block NL, et al. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group. Urology. 1997;50(3):330–336. PubMed.
- Iversen P, McLeod DG, See WA, et al. Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years. BJU Int. 2010;105(8):1074–1081. PubMed.
- Shipley WU, Seiferheld W, Lukka HR, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med. 2017;376(5):417–428. PubMed.
- Kunath F, Grobe HR, Rücker G, et al. Non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer. Cochrane Database Syst Rev. 2014;(6):CD009266. PubMed.
- Smith MR, Goode M, Zietman AL, et al. Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol. 2004;22(13):2546–2553. PubMed.
- Moretti C, Guccione L, Di Giacinto P, et al. Combined oral contraception and bicalutamide in polycystic ovary syndrome and severe hirsutism: a double-blind randomized controlled trial. J Clin Endocrinol Metab. 2018;103(3):824–838. PubMed.
- Wilde B, Diamond JB, Laborda TJ, et al. Bicalutamide-induced hepatotoxicity in a transgender male-to-female adolescent. J Adolesc Health. 2024;74(1):202–204. PubMed.
- Boccardo F, Rubagotti A, Battaglia M, et al. Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. J Clin Oncol. 2005;23(4):808–815. PubMed.
- Spagnolo L, Tienforti D, Moretto C, et al. Prevention of bicalutamide-induced breast events in patients with prostate cancer: a meta-analysis of randomized controlled trials. J Endocrinol Invest. 2025;48(7):1659–1668. PubMed.
- Wu B, Shen P, Yin X, et al. Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System. Br J Clin Pharmacol. 2023;89(2):440–448. PubMed.
- US Drug Enforcement Administration. Schedules of controlled substances: Schedule III. 21 CFR 1308.13. eCFR.
- World Anti-Doping Agency. The 2026 Prohibited List. In effect from January 1, 2026. WADA 2026 Prohibited List.