Getting Nerdy: The Buzz on Bicalutamide (August 2024)

We’ve talked about bicalutamide (bica) a few times in our articles:

• How do you know which T blocker to take? What is going on with bica or bicalutamide?
• 12/16 “The Beal Method” Optimizing Breast Development in Trans and Gender Diverse People
• Comparing Anti-androgens

Bicalutamide (brand name Casodex) is an androgen receptor antagonist. Androgen receptors are messengers in cells that react to either testosterone or dihydrotestoterone (DHT.) Once receptors are occupied, they “turn on” and tell the cell to make or do something. Bica takes up the space that testosterone or DHT would normally fit into, and stops the receptor from telling the cell to do anything.

Bica does not stop the body from making testosterone, so blood levels may not change (or may increase!) It does lower the body’s ability to use available testosterone – that’s why levels may increase: testosterone and DHT present in the body don’t get used, so there may be more of them circulating in the bloodstream. There is also some theories that the body might also increase testosterone production because it thinks that there aren’t enough available receptors.

Bica is a very effective androgen receptor antagonist.  

Each dose works for about five days to suppress the effects of T and DHT in the body.

Bica was developed for use in prostate cancer therapy. In research about its use for prostate cancer treatment, bica does not appear to increase cardiovascular (heart health) risks. (Pitrowski & Greenbert) However, using bica can increase the risks of other health issues, and those are important to know about.

We don’t have a lot of data about the risks of using bica in transgender populations, but there have been some studies, and we can use the data about its use in cisgender men and in cisgender women to inform our discussions of risk for our patients. (You can skip to the last section of this article for more information about bicalutamide in transgender medical care!)

We are most concerned about liver damage and toxicity when talking about bicalutamide. We watch for liver damage by symptoms and lab tests.

Symptoms of Liver Damage:

• nausea, vomiting, abdominal pain especially in the upper right side of the belly, fatigue and lethargy (which means feeling so tired and slow it prevents you from doing things you usually can,) loss of appetite, “flu-like” symptoms, dark urine, jaundice (which is the yellowing of the whites of the eyes and/or the skin.)

Lab Tests for Liver Damage:

• ALT and AST
  • ALT is alanine transminase. ALT is an enzyme that the liver uses to convert proteins into energy. ALT levels in the blood rise when the liver has been damanged. ALT blood levels can also rise as a result of a heavy workout!
  • AST is aspartate transminase. AST is an enzyme that the body uses to break down amino acids, which are the building blocks of proteins. Increased AST levels in the blood can indicate liver or muscle damage, or other conditions. Your AST levels can also be affected by your age, diet, or taking some medications.
  • A blood test result of a high ALT or AST does not mean that a person definitely has liver damage. If high ALT or AST levels are found, providers will often do further testing or repeat tests. One common step is to do a liver function test, which looks at more substances that can indicate liver health.
• Liver Function Tests (LFT)
  • LFTs are a panel of blood tests including alanine transminase (ALT,) aspartate transaminase (AST,) alkaline phosphatase (ALP,) gamma-glatamyl transferates (GGT,) serum bilirubin, prothombin time (OT, ) the international normalized ration (INR,) total protein and albumin.

Discussion of Risks and Recommended Use of Bicalutamide In The Treatment of Prostate Cancer

These risks are identified in the prescribing information about bicalutamide available from the FDA. This information is from studies on patients with advanced prostate cancer, who took 50 mg of bicalutamide a day, and typically also took an LHRH analog. Bicalutamide has also been used in the treatment of some cancers at a dosage of 150mg/day. This higher dosage is not currently used for prostate cancer.

LHRH agonists are medications that stop the body from creating hormones. They are also called GnRH agonists, and you may see that term more frequently in transgender medicine. In care for prostate cancer patients, bicalutamide 50 mg/day is taken in combination with an LHRH such as leuprolide (Lupron,) goserelin (Zoladex), triptorelin (Trelstar), and histrelin (Vantas). We also use some of these medications in transgender medical care, but not often in combination with bicalutamide.

The individuals in these studies had advanced prostate cancer. It is likely that their overall health was impacted by both the course of their cancers and prior treatments they had received such as radiation and chemotherapy.

This information applies to bicalutamide use in the treatment of prostate cancer. Recommendations are for bicalutamide use in prostate cancer treatment, not transgender medical care.

• Risk of Liver Injury and Hepatitis
  • Stopping bicalutamide due to hepatitis or significant increases in liver enzymes occurred in 1% of the study population.
  • Adverse event reports of abnormal liver function test results occurred in 7% of patients. These changes were frequently transient and rarely severe, resolving or improving with continued therapy or following cessation of therapy.
  • However, hospitalization and death due to severe liver injury have, on rare occassions, been associated with bicalutamide use. Transfeminine Science reports identifying 10 cases of severe liver injury attributed to bicalutamide use in cis men undergoing treatment for prostate cancer.
  • The prescribing information reports that damage to the liver generally occurred within the first three to four months of treatment.
  • What are the recommendations about prescribing bicalutamide for prostate cancer treatment?
    • Check liver enzymes before starting bica and at regular intervals during treatment.
    • Stop bica and go immediately to the hospital if experiencing any symptoms of liver injury: nausea, vomiting, abdominal pain, fatigue, anorexia, “flu-like” symptoms, dark urine, jaundice, or tenderness in the right upper side of the abdomen.
• Risk of Bleeding When The Individual Also Takes Coumarin (Warfarin)
  • There have been reports of individuals who were taking medications to thin their blood (anticoagulants) before they started bicalutamide experiencing serious bleeding after bica was started.
  • Recommendation: monitor the patient’s blood for bleeding risks and adjust the does of anticoagulant as needed
• Glucose Tolerance Impairment when the Individual Also Takes an LHRH (GnRH) agonist (the body has more difficulty controlling blood sugar levels and using blood sugars efficiently.)
  • Taking both medications may cause the body to utilize insulin less effectively. New diagnoses of diabetes have occurred, and individuals with existing diagnoses of diabetes may have more difficulty controlling their blood sugars.

Side Effects Reported by 20% or More of Patients Taking Bicalutamide IN COMBINATION WITH an LHRH Analog For The Treatment of Prostate Cancer*

• Hot Flashes – 53%
• Generalized Pain – 35%
• Back pain – 25%
• Asthenia (weakness or lack of energy) – 22%
• Constipation – 22%
• Pelvic Pain – 21% of patients

*This data does not extrapolate well to transgender and gender diverse people taking bica. In our clinical practice, it is well-tolerated. Side effects are rarely reported.

Bicalutamide Use in the Treatment of Androgen-Sensitive Conditions in Cis Women

In recent years, studies have looked at using bicalutamide for the treatment of other androgen-sensitive conditions, such as hirsutism (excess hair growth) associated with poly-cystic ovarian syndrome (PCOS,) and scalp hair loss in cis women.

Hirsutism Treatment

• One study compared two groups of patients:
  • patients taking oral contraceptives (the pill) and bicalutamide
  • patients taking oral contraceptives and a placebo.
• Individuals with high liver enzymes at the beginning of the trial were excluded.
• No significant differences in liver enzymes during or up to a year after treatment were identified.
• No significant adverse liver effects happened during the study.
• A slight rise in bilirubin levels was identified in the bicalutamide group. Bilirubin is a by-product of red blood cells and some muscle and liver cells breaking down, and can indicate liver or bile duct disease. (Moretti)

Scalp Hair Loss

• A 2023 study looked at using bicalutamide in injected scalp treatment for androgen-related hair loss in six cis women (this is called mesotherapy – see discussions of scalp and skin rolling in our article HAIR). The treatment was well tolerated, and increased scalp hair density was noticed, but did not appear to persist after treatment ended. The authors do not mention if they monitored patient liver toxicity. (Gomez-Zubiar)
• A 2020 retrospective study of 44 cis women taking 25 – 50mg/day of bicalutamide for scalp hair loss found slight increases in liver enzymes in 11.4% of participants (five total.) Liver enzymes returned to normal without stopping bicalutamide. A retrospective study looks at treatment records after a course of treatment rather than designing a study to ask specific questions of a type of treatment. (Fernandez-Nieto)
• Another 2020 retrospective study looked at 316 cis women taking bicalutamide daily in dosages from 5mg/day to 50mg/day. The majority of the study group took 10mg/day. Among these patients, nine had mildly elevated liver enzymes (2.85%,) and three discontinued use due to elevated liver enzymes. (Ismail)

Drug Interactions

Bicalutamide should not be taken with, or used with extreme caution when taken with:

• Medicines that thin the blood, like warfarin, phenprocoumon, or other anti-coagulants.
• Medicines that change how the body uses dopamine (dopamine antagonists) these may be drugs to treat or prevent nausea and to treat Parkinson’s Disease.
• Medications such as Levoketoconazole, which treats Cushing’s syndrome, which is a condition where the body makes too much cortisol.
• Medications such as methotrexate, which is used in chemotherapy and auto-immune treatments.
• Medications such as perperaquine, which is an anti-malarial.

In transgender medical care, another anti-androgen should be considered in patients who also take other medications or substances that can cause harm to the liver. This can include acetaminophen, alcohol, aspirin, some NSAIDs like diclofenac and ibuprofen (Advil,) some antibiotics like amoxcicillin-clavulanic acid (Augmentin,) and tetracycline, and anti-fungals like fluconazole. THIS IS NOT A COMPLETE LIST.

Now, What About Bicalutamide in Transgender Medicine?

WPATH SOC8 recommends against the routine use of bicalutamide. They make this recommendation because we don’t have a lot of data about using bicalutamide in transgender patients. Other organizations, including Fenway Health and the South African HIV Clinicians Society include bicalutamide in their recommendations for transgender medical care.

Transfeminine Science has written an excellent overview of bicalutamide in transgender medical care.

We will consider using it in individual cases because it is highly effective at what it does.

There may be greater risks in using an alternative anti-androgen for some patients, or previous use has not gotten the desired results. We utilize informed consent to make decisions about care with our patients.

We use bicalutamide differently in transgender medicine than in cisgender treatment. The biggest differences are:

1. We do not prescribe bicalutamide in combination with an LHRH/GnRH analog like leuprolide.
2. We prescribe a lower dose, like 25 to 50mg twice a week rather than 50mg/day.
3. We avoid it in medically fragile people.

Why Do We Do This?

There have been documented reports of liver toxicity and deaths in cis people taking bicalutamide. There have been anecdotal reports of liver damage transgender patients taking bicalutamide, and one report of a death. As we mentioned earlier, we don’t have a lot of studies about bicalutamide use in transgender medicine. We do have some, and we’ve included references at the end of this blog.

Recently, an article reported liver injury in a transgender 17 year old who had been taking bicalutamide 50/mg a day for three months. The patient was hospitalized for three days, and was discharged in stable condition. We do not know several important details about her care and what risks she may have had before and during treatment. We do not know for sure how much of a role bicalutamide played in her liver injury and subsequent death. But, this and article has increased discussion and scrutiny about bicalutamide use and concerns about bicalutamide in transgender care. In our practice, we use a lower dose of bica with our patients.

Three “posters” were developed and shared in 2023 that looked at safety data in transgender populations taking bicalutamide. Poster presentations are discussions of data that are less formal than published articles. Often they are shared at conferences, or are graduate student studies that may later be published.

Disclaimer: We were a part of one of these! Our founder, Dr. Beal is one of the authors of “Improving Access to Bicalutamide in Gender Affirming Medical Care.”

These three posters presentations shared the following conclusions from their data:

• Improving Access to Bicalutamide in Gender Affirming Medical Care, Bambilla A, Beal C, Vigil P
  • 67 patients, nine of which discontinued bicalutamide.
  • Top two reasons for discontinuation were achievement of treatment goals or alternative therapies available
  • 79% of patients did not experience AST/ALT levels outside of normal lab levels within six months of starting bicalutamide
• Bicalutamide use as antiandrogen in trans feminine adults – a safety profile; Vierregger K, Tetzlaff M, Zimmerman B, Dunn N, Finney N, Lewis K, Slomoff R, Strutner S; Department of Internal Medicine, University of California, Irvine
  • 143 transgender adults taking oral bicalutamide 25 mg/day
  • The study found
    • No elevated liver function tests (3x lab “normal” values) in any patient up to 24 months after starting bica
    • No increased AST or ALT liver enzyme tests among patients with these labs in the first six months of treatment
• Assessment of liver function and toxicity in transgender female adolescents prescribed bicalutamide; Burgener K, Herrick C, Wallendorf M, Lewis C, DeBosch B
  • 84 patients taking bicalutamide were compared to 69 taking GnRH agonists, spironolactone, or no anti-androgen in addition to estradiol
  • The study found
    • No difference in baseline ALT or AST
    • No difference in change to or maximum ALT or AST
    • No AST or ALT levels greater than 3x lab normal

If You Are A QueerDoc Patient Interested in Bicalutamide, We Will Discuss The Following With You:

• Getting bloodwork to see how your liver is working before starting bicalutamide.
• Getting monitoring bloodwork to see if your liver is harmed while taking bicalutamide.
• Other medications or substances that could harm your liver and ways to minimize potential harm.
• Not using other medications that could harm your liver.
• Pausing bica use if you are sick.
• Pausing bica use if you know you are going to be exposed to anything that could potentially damage your liver.
• Your overall health and any other risks you may have.
• The importance of stopping immediately and seeking emergency medical care if you show signs of liver damage.
• What dosages we use and our reasoning for why we use them.
• Goals for treatment and length of treatment.

What Does Bicalutamide Look Like?

A round white tablet with a manufacturer’s imprint, approximately 6mm in diameter (about 1/4″.) Images retrieved from Drugs.com.

Here’s our extended list of reference articles that we’ve used to inform our use of bicalutamide:

1. Yun GY, Kim SH, Kim SW, et al. Atypical onset of bicalutamide-induced liver injury. World J Gastroenterol. 2016;22(15):4062-4065. doi:10.3748/wjg.v22.i15.4062
2. Fernandez-Nieto D, Saceda-Corralo D, Jimenez-Cauhe J, et al. Bicalutamide: A potential new oral antiandrogenic drug for female pattern hair loss. J Am Acad Dermatol. 2020;83(5):e355-e356. doi:10.1016/j.jaad.2020.04.054
3. Neyman A, Fuqua JS, Eugster EA. Bicalutamide as an Androgen Blocker With Secondary Effect of Promoting Feminization in Male-to-Female Transgender Adolescents. J Adolesc Health. 2019;64(4):544-546. doi:10.1016/j.jadohealth.2018.10.296
4. Wadhwa VK, Weston R, Parr NJ. Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health-related quality of life benefits for osteoporotic men with prostate cancer. BJU Int. 2011;107(12):1923-1929. doi:10.1111/j.1464-410X.2010.09726.x
5. Hussain S, Haidar A, Bloom RE, Zayouna N, Piper MH, Jafri SM. Bicalutamide-induced hepatotoxicity: A rare adverse effect. Am J Case Rep. 2014;15:266-270. Published 2014 Jun 20. doi:10.12659/AJCR.890679
6. Helga M. Gretarsdottir, Elin Bjornsdottir, Einar S. Bjornsson; Bicalutamide-Associated Acute Liver Injury and Migratory Arthralgia: A Rare but Clinically Important Adverse Effect. Case Rep Gastroenterol 3 September 2018; 12 (2): 266–270. https://doi.org/10.1159/000485175
7. Ismail FF, Meah N, Trindade de Carvalho L, Bhoyrul B, Wall D, Sinclair R. Safety of oral bicalutamide in female pattern hair loss: A retrospective review of 316 patients. J Am Acad Dermatol. 2020;83(5):1478-1479. doi:10.1016/j.jaad.2020.03.034
8. Improving Access to Bicalutamide in Gender Affirming Medical Care, Bambilla A, Beal C, Vigil P
9. Assessment of liver function and toxicity in transgender female adolescents prescribed bicalutamide; Burgener K, Herrick C, Wallendorf M, Lewis C, DeBosch B
10. Angus, L. M., Nolan, B. J., Zajac, J. D., & Cheung, A. S. (November 2023). Bicalutamide as an anti-androgen in trans people: a cross-sectional study. AusPATH 2023 Symposium. [URL] [PDF] [Trans Health Research Blog Post]
11. Burgener, K., DeBosch, B., Lewis, C., Wallendorf, M., & Herrick, C. (May 2023). Assessment of Liver Function and Toxicity in Transgender Female Adolescents Prescribed Bicalutamide. Hormone Research in Paediatrics, 96(Suppl 3 [Abstracts of the 2023 Pediatric Endocrine Society (PES) Annual Meeting’ to Hormone Research in Paediatrics]): 377–378 (abstract no. 6232). [DOI:10.1159/000531602] [PDF]
12. Karakılıç Özturan, E., Öztürk, A. P., Baş, F., Erdoğdu, A. B., Kaptan, S., Kardelen Al, A. D., Poyrazoğlu, Ş., Yıldız, M., Direk, N., Yüksel, Ş., & Darendeliler, F. (2023). Endocrinological Approach to Adolescents with Gender Dysphoria: Experience of a Pediatric Endocrinology Department in a Tertiary Center in Turkey. Journal of Clinical Research in Pediatric Endocrinology, 15(3), 276–284. [DOI:10.4274/jcrpe.galenos.2023.2023-1-13]
13. Vierregger, K., Tetzlaff, M., Zimmerman, B., Dunn, N., Finney, N., Lewis, K., Slomoff, R., & Strutner, S. (May 2023). Bicalutamide Use as Antiandrogen in Trans Feminine Adults – A Safety Profile. NTHS 2023 Symposium. [Poster PDF] [Symposium Session] [Symposium Abstracts/Program Book]
14. Vierregger, K. S. (November 2023). Bicalutamide Use as Antiandrogen in Trans Feminine Adults – A Safety Profile. USPATH 2023 Symposium. [Symposium Schedule]
15. Warus, J. (November 2023). Safety of Bicalutamide as Anti-Androgenic Therapy in Gender Affirming Care for Adolescents and Young Adults: A Retrospective Chart Review. USPATH 2023 Symposium. [Symposium Schedule]
16. Wilde, B., Diamond, J. B., Laborda, T. J., Frank, L., O’Gorman, M. A., & Kocolas, I. (2023). Bicalutamide-Induced Hepatotoxicity in a Transgender Male-to-Female Adolescent. Journal of Adolescent Health, 74(1), 202–204. [DOI:10.1016/j.jadohealth.2023.08.024] 2024
17. Burgener, K., DeBosch, B., Wang, J., Lewis, C., & Herrick, C. J. (2024). Bicalutamide does not raise transaminases in comparison to alternative anti-androgen regimens among transfeminine adolescents and young adults: a retrospective cohort study. medRxiv, preprint. [DOI:10.1101/2024.02.21.24302999v1] [PDF]
18. Fuqua, J. S., Shi, E., & Eugster, E. A. (2024). A retrospective review of the use of bicalutamide in transfeminine youth; a single center experience. International Journal of Transgender Health, advance online publication. [DOI:10.1080/26895269.2023.2294321]
19. Shumer, D., & Roberts, S. A. (2024). Placing a Report of Bicalutamide-Induced Hepatotoxicity in the Context of Current Standards of Care for Transgender Adolescents. Journal of Adolescent Health, 74(1), 5–6. [DOI:10.1016/j.jadohealth.2023.10.010]

Additional References Used In This Article:

• Zachary Piotrowski, Richard E. Greenberg, Chapter 55 – Antiandrogen Monotherapy in the Treatment of Prostate Cancer, Editor(s): Jack H. Mydlo, Ciril J. Godec, Prostate Cancer (Second Edition), Academic Press, 2016, Pages 515-521, ISBN 9780128000779, https://doi.org/10.1016/B978-0-12-800077-9.00055-4.(https://www.sciencedirect.com/science/article/pii/B9780128000779000554)
• Costanzo Moretti, Laura Guccione, Paola Di Giacinto, Ilaria Simonelli, Caterina Exacoustos, Vincenzo Toscano, Cecilia Motta, Vincenzo De Leo, Felice Petraglia, Andrea Lenzi, Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and Severe Hirsutism: A Double-Blind Randomized Controlled Trial, The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 3, March 2018, Pages 824–838, https://doi.org/10.1210/jc.2017-01186
• Gomez-Zubiaur A, Andres-Lencina JJ, Cabezas V, Corredera C, di Brisco F, Ferrer B, Rodriguez-Villa A, Subiabre-Ferrer D, Valenzuela C, Diez DV, Ricart JM. Mesotherapy with Bicalutamide: A New Treatment for Androgenetic Alopecia. Int J Trichology. 2023 Jan-Feb;15(1):39-40. doi: 10.4103/ijt.ijt_78_21. Epub 2023 Apr 19. PMID: 37305191; PMCID: PMC10251290.
• Drug-Induced Hepatotoxicity (Medscape)
• Mayo Clinic Drugs and Supplements: Bicalutamide (Oral Route)
• Highlights of Prescribing Information (FDA)
• Mayo Clinic Liver function tests
• Alanine Aminotransferase (ALT) Test: What Does It Mean? (WebMD)
• AST Test (MedlinePlus)
• Bicalutamide Pill Images (drugs.com)

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