How do you know which T blocker to take? What is going on with bica or bicalutamide?

What’s an Anti-Androgen?

Anti-androgens (blockers) either suppress androgen production in the body or, more commonly, block cell receptors for androgens, thus limiting their usability in the body. Androgens are a group of steroid hormones that include testosterones. Sometimes anti-androgens are also called testosterone blockers. Anti-androgens that block cell receptors may initially increase the amount of testosterone in the body – and thus blood work results – but the testosterone isn’t being used by the cells. 

They all work to limit the effects of testosterone in the body!!!

For adults with bodies that make larger quantities of testosterone, three of the most commonly prescribed anti-androgens in the United States are:

• Spironolactone (Aldactone)
• Finasteride (Propecia, Proscar) or dutasteride (Avodart)
• Bicalutamide (Casodex)

*if you want to learn more but prefer video content pop over to QueerCME to enroll in QueerU where there is a webinar on anti-androgen use accredited for CE/CME.

Less commonly we use leuprolide (lupron). We won’t really address it much in this blog.

In adolescents with bodies that make larger quantities of testosterone, we do commonly prescribe leuprolide (lupron,) which is actually a GnRH agonist.  GnRH agonists reduce the release of precursor hormones by the pituitary gland so that the testes then produce less testosterone.  We can also use bicalutamide or spironolactone if access to leuprolide is poor. You can learn more about our adolescent gender-affirming care here.

At QueerDoc, we try to help you choose the best anti-androgen option for your goals and your current health status. We do not conflate gender identity with goals for gender-affirming care at QueerDoc.

There is no one way to be gender diverse, no one way to be trans, and we want to support your way.

How do I decide?

Blockers may or may not be a fit for your goals. Here we will review some of the things we think about and explore when patients are looking at blockers. Other things that may affect this decision are supply, access, cost, and insurance coverage (but we won’t review those today).

Goals that affect this decision are:

• desired rate of treatment effects
  • To see the effects of estrogen faster, anti-androgens will help
  • You can do gender-affirming care without any anti-androgens if a slower rate of change fits your goals
    • Estrogen, preferably in combination with progesterone, can suppress testosterone production, particularly when using injectable forms, without using an anti-androgen⁺
    • This minimizes the number of medications you have to take and minimizes potential side effects and medication interactions
    • The ultimate potential for change is unlikely to be affected as it is not based on rate of change but on your underlying pre-existing genetics, duration or previous exposure to testosterone, and your individual response to hormones which is poorly understood⁺
• desire for breast development
  • Limited studies showed that breasts may be smaller in people treated with spironolactone¹
    • The theory is that spironolactone may cause early breast bud fusion
    • The potential solution is to delay start of spiro by 6-9 months from start of estrogen
  • Bicalutamide may cause improved breast development based on increased estrogen receptor activity in breast tissue or increased levels of estrogen aromatized from testosterone²
    • The “may” is pretty big! It’s important to remember that all effects seen will be based on your body’s pre-existing genetics, your body’s duration of exposure to testosterone, and some stuff we don’t understand yet!

• desire to reduce or maintain erectile function
  • Finasteride has the highest rates of decreasing erections³
  • Bicalutamide seems to do this the least⁺

Health things that can affect your choice of anti-androgen:

• Spiro
  • Consider avoiding if you have gout, kidney health issues, liver health issues, or electrolyte issues. Spiro may be less safe for you.³
  • Consider taking it if you have acne or high blood pressure. Spiro may help with your gender care and is used to treat these conditions as well.
• Finasteride
  • Consider avoiding if you have liver health issues³, a strong family history of prostate cancer (particularly high-grade or at a young age,³), or depression⁺. Finasteride may be less safe for you.
  • Consider taking if you are sensitive to medications and/or frequently have side effects with medication use. Finasteride has the lowest number of potential side effects.³
  • Important!  Other people handling this medicine should wear gloves!
• Bicalutamide
  • REALLY, REALLY consider avoiding if you have liver issues, drink heavily (either regular use or binge drinking,) or have health conditions that make you more medically fragile (like cardiovascular disease or some autoimmune conditions.) You might die from it, so really consider!⁴

• Consider avoiding if you are over 35, have diabetes, have anemia, or have bone health issues. Bicalutamide may be less safe for you.⁴
• Consider taking if you are younger, particularly in adolescence or early 20s.¹⁺ If access to leuprolide is limited, bicalutamide may be a good choice for you.

Frequency of labs is another thing to consider.

Labs require transportation, time, and money! The below recommendations are for lab monitoring if you don’t have any side effects or symptoms.

If something feels off in your body, talk to your provider! It might be important to check labs early.

• Spiro ³⁺
  • Baseline labs checking your kidney function (Cr) and potassium (K) are recommended. Then repeat within 4-12 weeks. Repeat every three months for the first year. Then every 6-12 months. However, if you are under 45, otherwise healthy, and staying on a dose <100mg daily, you can probably forgo labs safely.
• Finasteride ³⁺
  • No baseline labs are needed, but a prostate lab (PSA) is recommended around six months. Consider checking PSA annually.
• Bicalutamide³⁺
  • Baseline liver labs (AST/ALT). Consider checking in 2-4 weeks. Repeat every three months for the first year. Then every 3-6 months. Consider annual hemoglobin and hematocrit, ECG, and luteinizing hormone levels.
  • Tracking testosterone levels in the presence of bicalutamide can be challenging. Bica very frequently causes initial increases in testosterone levels. (Remember, it blocks testosterone and dihydrotestosterone receptors, so the body can’t use those hormones.)

What about bica?

At QueerDoc, we get questions and referrals about bicalutamide all the time.

We want to spend some extra time discussing how we use it.

Bicalutamide has less available data about use in gender-diverse folx than spiro and finasteride. It was designed to treat prostate cancer, and patients are usually older people with prostrates who are not taking estrogen or other forms of gender-affirming medications. What we know about the side effects and risks might not relate to our gender-diverse population at all because they are reported from patients also on other anti-cancer medications at the same time. That being said, it is the only data we have.

The scary thing about bicalutamide is it has killed some people from sudden liver failure.

This mostly seems to have happened in people over the age of 35 with other significant health conditions who frequently had previously taken flutamide.⁴  However, there was one anecdotal story of a gender-diverse person dying. More details are now known:

A trans person who was “otherwise healthy” but was over the age of 60 was prescribed bicalutamide. Unfortunately, this person died from bicalutamide.

Liver failure does seem to happen more commonly within the first month of treatment, so it is rather difficult to get labs to identify liver problems early. Most people can’t go to the lab daily or even weekly.

We want to stress that any warning signs of liver problems should be treated seriously and investigated:

•         Pain in the right upper side of your tummy
•         Yellowing of the eyes or skin
•         Itching
•         Feeling really tired or confused
•         Swelling of your hands, feet, or belly

If you experience any of these, stop bica right away and go to an emergency department!

In order to reduce the risk of stress on the liver and death from liver problems, we recommend the lowest most effective dose of bicalutamide.

Here’s some of what we’ve found in clinical practice:

Currently, we have found one 50mg tablet by mouth twice weekly to be effective for gender-affirming care for most people.⁺

Bicalutamide has a long half-life which means once you take it, it lasts for about 6 days at an effective dose in your body!³  Theoretically, you could take it every 6 days, but it seems harder to remember to take something every 6 days instead of twice a week. Also, we have several patients who take half a tablet every day with positive results.

We recommend liver labs every three months in folx who feel confident in self-monitoring side effects and seeking emergency care if needed.

In folx who feel less confident in self-monitoring or more uncomfortable with the unknown risk, we recommend labs within 4 weeks of starting, then every 3 months.

Before starting this or any other medication at QueerDoc, we do have a thorough informed consent conversation. QueerDoc also has you sign a consent agreement. While we support the move away from signed documents for gender-affirming care, we have decided to continue this practice for now. Since we are pioneering a new model of gender-affirming care – a totally online clinic founded on transparency, evidence-based medicine, and informed consent, we feel the extra layer of educational material in the consent document and the extra layer of legal protection appropriate for us and our patients. We have recently updated our forms to minimize binary gendered language in them.

When to stop bicalutamide?

Adults

We do recommend considering stopping bicalutamide before the age of 35 or after the completion of the first two to three years of “Second Puberty.”⁺

We recommend this because the long-term safety data is so unknown, and the risk of death due to liver complications correlates to some degree with advancing age and previous exposure to medications like bicalutamide.⁴
At this point in your gender journey, you could transition to a different blocker with more safety data. You might no longer need a blocker, especially if you use injectable estrogen and progesterone. You may have surgery to remove your testicles if that fits your goals. You may decide to continue despite these risks, but we like to have a very transparent conversation with you about that!

For younger people (11-22ish)

with no other significant health conditions taking bicalutamide we like to continue it through their early 20s to significantly reduce the risk of dysphoria-triggering secondary sex characteristic formation.⁺

We then recommend considering changing the anti-androgen, using estrogen/progesterone alone, and/or orchiectomy.

At QueerDoc, we would prefer to use leuprolide, or lupron, for gender diverse folx in puberty,

But we frequently work with patients who don’t have access to it due to insurance coverage issues. Leuprolide is expensive without coverage (more than $1000 per month). Therefore, we are thrilled to be able to offer bica because research shows medically supporting gender-diverse adolescents gives them better outcomes:

•         less depression⁶
•         less thoughts of suicide⁷
•         improved global functioning⁸

Bicalutamide may be a more effective androgen blocker option in these youth than spironolactone as it does not affect cortisol levels, breast development, or short-term bone health.

Both bicalutamide and spironolactone cross the blood-brain barrier, so in theory, youth would eventually need some exposure to sex steroids (testosterone or estrogen) to help with further neurocognitive development. However, in youth with high levels of testosterone on bicalutamide, the testosterone is converted to estrogen which is supportive of both bone and neurocognitive development.

This is a summary of our current practices. Recommendations evolve over time as we have more data, so stay tuned for updates when available.

This blog is a compilation of quite a bit of medical training, literature review, and clinical practice. It was written with a fair bit of medical terminology. It was written in response to questions from patients who have done a lot of research on their own and to questions from other providers. This means it may be hard to follow for people without that training or research background. Much of this is summarized more simply in a chart we published a bit ago!

You made it so far! Want to keep learning with us?

Join us at QueerCME to learn more. Enroll in QueerU to gain access to a 90 minute CE/CME certified webinar on antiandrogen use in gender affirming medical care.

References

1. Wierckx K, Gooren L, T’Sjoen G. Clinical review: Breast development in trans women receiving cross-sex hormones. J Sex Med. 2014 May;11(5):1240-7.
2. 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
3. Up-to-date: adverse events and contraindications for spironolactone, finasteride, and bicalutamide
4. 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
5. Yun GY, Kim SH, Kim SW, Joo JS, Kim JS, Lee ES, Lee BS, Kang SH, Moon HS, Sung JK, Lee HY, Kim KH. Atypical onset of bicalutamide-induced liver injury. World J Gastroenterol. 2016 Apr 21;22(15):4062-5. doi: 10.3748/wjg.v22.i15.4062. PMID: 27099451; PMCID: PMC4823258.
6. Olson K.R., Durwood L., DeMeules M., & McLaughlin K.A. (2016). Mental health of transgender children who are supported in their identities. Pediatrics, 137(3), e20153223.
7. Turban JL, King D, Carswell JM, Keuroghlian AS. Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation. Pediatrics. 2020;145(2):e20191725. doi:10.1542/peds.2019-1725
8. Costa R., Dunsford M., Skagerberg E., Holt V., Carmichael P., & Colizzi M. (2015). Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. Journal of Sexual Medicine,12, 2206–2214.
9. 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 Jun;107(12):1923-9. doi: 10.1111/j.1464-410X.2010.09726.x. Epub 2010 Oct 15. PMID: 20950306.

+Clinical experience