Bicalutamide for Trans Feminine Spectrum Folks
The most common anti-androgen used for trans women in this country is spironolactone. Spironolactone is a medication that is primarily used as a diuretic for people with high blood pressure. It blocks the steroid hormone aldosterone from having an effect on the kidneys and results in water loss from the body, which lowers the water volume inside the blood and therefore lowers blood pressure. The molecular structure of spironolactone is similar enough to testosterone that it also blocks the testosterone receptor fairly well. Many trans feminine patients tolerate spironolactone extremely well. However, like any medical intervention, there are others with whom the side effects are intolerable. I have seen many patients that feel non-functional due to the increase in urination. Or, folks that get dizziness as a result of lowered blood pressure. These intolerable side effects are not particularly surprising in this demographic because many trans feminine folks also experience issues such as hypermobile Ehlers-Danlos Syndrome, Mast Cell Activation Syndrome and Postural Orthostatic Hypotension, which are other disorders that can have issues with dizziness or blood pressure stability.
Bicalutamide (brand name Casodex, nickname Bica) is used primarily for the treatment of advanced prostate cancer. Unlike spironolactone, bicalutamide is a direct and specific blocker of both the DHT and the testosterone receptor. Seems like it should get some serious consideration in the treatment of trans feminine patients, right? Well, many providers are too nervous to veer off of the standards of care to offer it as an option, so it is not readily available at most clinics. One of the major side effects from Bica is inflammation of the liver (hepatitis), as evidence by increased liver enzymes. The study that the UCSF guidelines quote as their reason for avoiding bicalutamide looked at 3000 advanced stage prostate cancer patients. The study notes that they cannot definitively say that the increased liver enzymes were from the Casodex, although it is likely that for at least some of these patients, the medication was the cause (PMID: 8560681). I do, however, find it difficult to apply these results from advanced cancer patients to my fairly healthy trans patients. The one study that we do have using bicalutamide in 23 transwomen did not show elevated liver enzymes (PMID: 30612811). The major side effect from the medication? Breast development (which can be a side of effect of spironolactone as well).
Let’s just say that bicalutamide carries a significant risk of elevated liver enzymes. Do you know what else carries a very clear risk of elevated liver enzymes? Tylenol. Tylenol is one of the absolute worst medications for the liver and I can buy it everywhere. Even worse, tylenol is an ingredient in many combo medication products, meaning the risk that a patient may accidently over-consume Tylenol is higher. There are many medications that carry the risk of liver strain actually, and we have a very reliable lab test to watch and observe how the liver is tolerating a medication.
If you happen to be one of those patients that does not tolerate spironolactone and need a reliable way to shut down the effect of testosterone in your body, your choices become more narrow. There are a few other choices (dutasteride, finasteride, and injectable estradiol), however, none of those options are direct and specific blockers of DHT and testosterone. If you need to shut down T in your body and are not loving your mainstream options, do you just go untreated due to the potential risk of liver toxicity? The alternative risks of untreated gender dysphoria, such as alarmingly high suicide rates among transgender individuals (35% - PMID: 30677012) further underline the need for informed choices. Transgender veterans fair even worse, with up to 66% of them having attempted or planned their suicide at some point in their lives (PMID: 26878597). It feels short-sided and inappropriate to not consider this as an option for this population.
In the transgender community, physicians have historically acted as gatekeepers to essential medical interventions. Similarly, reluctance among some physicians to explore alternative treatments mirrors this history. I believe strongly in informed consent and they deserve to be informed about this option!
I am grateful for the work of the WPATH and UCSF and I think their guidelines have opened up avenues of care for many providers. It can be overwhelming to know where to turn when you start this work. And, I think we need to keep exploring and advancing our field, so our patients get the absolute best assortment of choices to navigate their transition.