Androgen receptor blockers: Spironolactone and Bicalutamide
Spironolactone and Bicalutamide are two androgen receptors blockers used in feminizing HRT.
If spironolactone is more widely prescribed, bicalutamide should be preferred.
Since they block the reception and not the production, no decrease of androgen levels will be shown on the blood test result.
Androgen receptor blockers are molecules which have the capacity to bind to the androgen receptors. Remember the image of the key and keyhole? Androgen receptor blockers are like keys that fit in the keyhole, but can’t open it. And not only it can’t open it, but it’s stuck in there so that the keys that could actually open it can no longer get in. So, a bit like when your key breaks in the lock before you open the door…
What this also means is that what is blocked is the reception of androgens (and hence their effects), but not the production.This doesn’t make them less effective. If your levels of estrogens are not blocking the production of testosterone (which would be the reason you want to take androgen blockers), then testosterone will still run in your system, and you will still see it on the blood test results. This doesn’t mean the treatment doesn’t work, and you should judge this by the results you feel and observe on body changes.
The main drugs in the category are Spironolactone and Bicalutamide. Flutamide is a sort of earlier and much more risky version of bicalutamide, and it has been removed from the market in many countries.
😐 Spironolactone
This is actually a diuretic medication in the first place (i.e. intended to make you pee). Its anti-androgenic function is one of its secondary effects. In addition to working as a receptor blocker, it also has a small 5a-reductase inhibition power (prevents conversion of Testosterone into its more potent form DHT - read more in the dedicated section).
One issue is that it also blocks other receptors, mainly the ones of progesterone, and cortisol, which can lead to undesired effects.
The main issue reported by transfem people using it is its diuretic effect.
It also comes with risks of hyperkalemia, which is an excess of potassium. This can have dangerous consequences on cardiac health. For this reason, you might want to monitor your diet, keeping an eye on your potassium and sodium intake.
Finally, many report poor efficacy as an androgen blockers. All of the above gives a pretty bad reputation to spironolactone in the trans community, but it remains a widely prescribed drug in feminizing HRT - especially in the USA.
| Products name in Sweden | Dose | Blood values to monitor |
|---|---|---|
| Spironolactone (sometimes Aldactone in other countries) | Between 50 and 200 mg per day | Potassium, Sodium, ALAT, ASAT, GGT |
Pros
- Convenient and usually cheap
Cons
- Limited efficacy
- Makes you pee
- You might need to monitor your diet to avoid potassium excess
✅ Bicalutamide
As opposed to spironolactone, bicalutamide has been conceived as a pure androgen blocker in the first place, in order to treat prostate cancer, and later on hirsutism, and as a puberty blocker. It blocks the reception of androgens in a very efficient way, without blocking other receptors, hence limiting the secondary effects. It is increasingly considered one of the best alternatives among androgen blockers, along with GnRHa.
A study showed that it has feminizing effects by itself, as the testosterone running in the body without finding a place to bind is eventually aromatized into estradiol, giving higher estradiol levels than when testosterone finds and binds to its receptors. However, it is safer to never take an androgen blocker by itself, and always add estrogens.
| Products name in Sweden | Dose | Blood values to monitor |
|---|---|---|
| Bicalutamide, Casodex, Bicalustad | 25 to 50mg a day | ALAT, ASAT, GGT |
Pros
- Very efficient
- Nearly no secondary effects and low risks for health
Cons
- Sometime a bit expensive
- Practitioners are a bit reluctant to prescribe (because uniformed)
- You have to monitor your liver health (though the risks remains considerably lower than with synthetic progestins like Androcur)
About the risks of liver failure
Taking bicalutamide often comes with warning of liver failure. If this risk exists, it should, however, be relativized. This risk remains extremely rare: in 15 years of existence and usage, the drug has led to 14 reported cases of liver failure in the world.
A study on 4052 prostate cancer patients taking 150mg of bicalutamide daily showed that only 3.4% of the patients developed abnormal levels of liver enzymes. In comparison, we find the number rising to 10 or even 20% for people treated with Androcur (cyproterone acetate). Besides, in feminizing HRT, the common dosage is 50mg a day.
As a safety measure, the best remains to regularly monitor your liver enzyme levels: ALAT, ASAT, GGT. You can see an increase of them in the first few months of the treatment, which usually resorbs after a while.
Besides, remain attentive to symptoms of fulminant hepatatis (fatigue, nausea, abdominal pain, jaundice, confusion…)
About the cardiovascular risks
If your practitioner is reluctant to prescribe bicalutamide for you, invoking cardiovascular risks, this is known to be a conclusion inferred from a different case. Nothing shows that bicalutamide brings, by itself, cardiovascular risks. Those risks are inferred from the cases of cis-men in treatment for prostate cancer. Those patients end up with sex hormone deficiency, since they do not complement with estradiol intake. It is sex hormone deficiency that bears increased risks of cardiovascular diseases; these risks do not concern transfem people compensating with estrogens.Dosage
A dosage of 50mg/day is usually sufficient. If your testosterone has already been lowered with negative feedback, half this dose can be enough to block the leftovers of testosterone (take one 50mg pill every other day). If you feel masculinising effects coming back, return to 50mg/day. Theoretically, 50mg of bicalutamide can block around 200 ng/dl of testosterone (1mg of bica blocks 4ng/dl).
Keep in mind that it will not affect the levels of testosterone shown in the blood test results. This is absolutely normal.
More resource on bicalutamide
General information articles on bicalutamide :
- Bicalutamide – Wikipedia
- Medical uses of bicalutamide – Wikipedia
- Side effects of bicalutamide – Wikipedia
- Pharmacology of bicalutamide – Wikipedia
- Comparison of bicalutamide with other antiandrogens – Wikipedia
- FAQ par transfemscience.org
Specific sections with information on bicalutamide (and other nonsteroidal antiandrogens) in transgender women :
- Medical uses of bicalutamide § Transgender hormone therapy – Wikipedia
- Transgender hormone therapy (male-to-female) § Nonsteroidal antiandrogens – Wikipedia
- Flutamide § Transgender hormone therapy – Wikipedia
- Nilutamide § Transgender hormone therapy – Wikipedia
- Specific sections with information on bicalutamide (and other nonsteroidal antiandrogens) in cisgender women :
- Medical uses of bicalutamide § Skin and hair conditions – Wikipedia
- Bicalutamide § Research – Wikipedia
- Flutamide § Skin and hair conditions – Wikipedia
- Nilutamide § Skin and hair conditions – Wikipedia
Specific sections with information on bicalutamide in boys with precocious puberty (potentially relevant to the use of bicalutamide as a puberty blocker in adolescent transgender girls) :
- Medical uses of bicalutamide § Male early puberty – Wikipedia
Scientific Literature
- Relevant literature excerpts on bicalutamide in transgender women
- Care of Transsexual Persons (Gooren, 2011)
- Bicalutamide as an Androgen Blocker with Secondary Effect of Promoting Feminization in Male to Female (MTF) Transgender Adolescents (Neyman, Fuqua, & Augster, 2017)
- Bicalutamide as an Androgen Blocker With Secondary Effect of Promoting Feminization in Male-to-Female Transgender Adolescents (Neyman, Fuqua, & Eugster, 2019)
Literature reviews on bicalutamide (and other nonsteroidal antiandrogens)
- Bicalutamide § Further reading – Wikipedia
- Bicalutamide / Nonsteroidal Antiandrogens – PubMed (filter search results by « Review » in the left-hand column)
Regulatory Body Materials
- Casodex (bicalutamide) 50 mg FDA (US) label
- Casodex (bicalutamide) 150 mg MHRA (UK) prescribing information
- Casodex (bicalutamide) 150 mg MHRA (UK) patient leaflet (PDF)
- Casodex (bicalutamide) 50 and 150 mg MHRA (UK) public assessment report
- Bicalutamide (Casodex) as an Antiandrogen for Transgender Women Megathread
- Bicalutamide frequently asked questions (FAQ) and common misperceptions
- Scientific Literature about Bicalutamide
- Hormone Therapy for Transgender Women 101 – u/Alyw234237
- Recent Study: Bicalutamide in MtF Adolescents (value as an AA and for promoting feminisation) – u/Ambrosia25
- Calculation and discussion of bicalutamide dosage potentially required for puberty blocking in MtF trans girls – u/Ambrosia25 (direct link to the document/email being discussed here)
- Rise in blood levels of bicalutamide for various dosages (graph) – u/Ambrosia25
- Indirect evidence that bicalutamide is able to provide the same benefits as flutamide for scalp hair loss – u/Ambrosia25
- A ranking of AAs in terms of Safety, Effectiveness, Tolerability and Cost (inexpensiveness) – u/Ambrosia25
- New publication: Bicalutamide as an Androgen Blocker With Secondary Effect of Promoting Feminization in Male-to-Female Transgender Adolescents (Neyman, Fuqua, & Eugster, 2019) – u/Alyw234237
- Hormone Therapy for Transfeminine Non-Binary Individuals and Femboys 101 – u/Alyw234237
News and Blogosphere
- Bicalutamide, a new anti-androgen for trans women and girls (Jones, 2018)
⛔ Flutamide
It is considered an “ancestor” of bicalutamide. It works the same way, but with much more risks and side effects, especially on liver function. It should NOT be prescribed by any practitioner, and has been put off market in many countries.