Anti-androgens, also known commonly as Testosterone blockers, are medications with the sole purpose of blocking or limiting the production of testosterone in your body.
Spironolactone – Spironolactone, also known as spiro, is a potassium-sparing diuretic originally used to treat prostate cancer in men and fluid build-up due to heart failure. In transgender women, it is used as an off label anti-androgen since it is a 5α-reductase inhibitor. A 5α-reductase inhibitor limits testosterone from binding and the conversion of Dihydrotestosterone (DHT) in natal men. Since spiro is a potassium-sparing diuretic, your body may have trouble absorbing sodium when you are on this medication. It is common for trans women to have salt cravings when on spiro. Spiro also has a common side effect of you needing to use the bathroom frequently.
Spiro is currently the standard anti-androgen used in the United States. Commonly, spiro will start at anywhere between 25-100mg taken once or twice a day and can range up to 100 to 400mg. However, once you get into the medication’s higher doses, the side effects get much worse, while the testosterone-blocking does not increase.
Common side effects are drowsiness, high potassium levels, headaches, and brain fog. Furthermore, for some trans women, spiro does not work well. For instance, I was on Spiro for the first 8 months of my transition, and it did not properly block my testosterone. I believe that other types of blockers, like bicalutamide, would have been a better substitute.
The half-life of spiro is about 12 hours; you want to be dosing twice a day for optimal results. If you are taking spiro, you need to limit the amount of potassium you intake. The reason being, spiro increases the amount of potassium in your blood, intaking too much potassium can cause health problems or an overdose.
Cyproterone acetate – Cyproterone acetate is one of the most commonly used anti-androgen in the world. However, it is not used in the United States since the FDA has not approved it. Cyproterone acetate is a progestin. Progestins and progesterone may help your breast look fuller and help with nipple and areola growth.
Cyproterone acetate has a similar effect to a GnRH modulator. A GnRH modulator stimulates the LH (luteinizing hormone) and FSH (follicle-stimulating hormone). The LH and FSH in natal men are the signals to the testicles to produce hormones. If you shut down the signals, then your body no longer produces high testosterone levels, which is optimal in the case of transgender women.
Cyproterone acetate itself is a potent medication and can have unpleasant side effects, such as depression, fatigue, high prolactin production, and liver health problems. Dosing ranges from 6.5 to 12.5 mg daily and up to 50 mg, or even 100 mg. Lower dosages of Cyproterone acetate can get effective testosterone suppression without the nasty side effects. Taking higher doses, such as 50 to even 100 mg, can be dangerous and unnecessary. Taken orally, the half-life of Cyproterone acetate is about 36 hours, so taking it every day is a good idea.
Important footnote, if you are taking Cyproterone acetate, you need to be routinely checking for prolactin since Cyproterone acetate increases the production of prolactin. Higher prolactin levels can cause prolactinoma, a type of noncancerous tumor that develops at the base of your brain.
Lupron – Short for Leuprorelin, is the standard puberty blocker worldwide. However, it can also be utilized for trans men and women over the age of 18. Lupron is a GnRH modulator, meaning that lupron turns off your LH (luteinizing hormone) and FSH (follicle-stimulating hormone). For this reason, lupron tends to be the first choice if available. However, for those over the age of 18, you may have a hard time getting lupron covered by insurance. To pay for the medication out of pocket, it can be upwards of $1,700 USD.
Lupron itself is an injection that can be taken intramuscular or subcutaneously, which only needs to be administered every 3-6 months. An important thing to keep in mind if you are getting on lupron is that you may see the opposite of what you want for the first month, such as increased masculinization for trans girls or increased feminization for trans men. The reasoning being, lupron shuts down the signal to your testicles or ovaries; it overloads both LH (luteinizing hormone) and FSH (follicle-stimulating hormone) before it shuts down completely.
Dosing is almost always 3.5-7.5 mg per month, but the amount you take depends on when you want your next dosage. Lupron’s side effects are similar to other types of anti-androgens, with the common ones being fatigue, headaches, and nausea. Specifically, in the case of lupron, if you are a person on puberty blockers for a long time without testosterone or estrogen supplementation, you will lose bone strength.
Primary androgens, such as estrogen or testosterone, play a large role in bone strength. If you plan on being on blocked rs or puberty blockers, incorporating calcium supplements will help with your bone strength and help prevent osteoporosis down the line.
Bicalutamide – Bicalutamide is not as common as either spironolactone or cyproterone acetate, but it is available worldwide for use. Bicalutamide works by stopping androgen receptors’ production and the conversation of testosterone to dihydrotestosterone (DHT).
One of Bicalutamide’s unique attributes is that your blood work will still show the levels of testosterone. However, your body is not using any of the testosterone that is shown. In the case of transgender women, Bicalutamide is used in conjunction with estrogen. The estrogen that is being used will lower your testosterone since estrogen in of itself is an anti-androgen. Bicalutamide can also be utilized for trans girls who have high levels of DHT while still have lower levels of Testosterone.
Over the years, Bicalutamide has drastically increased in popularity and usage compared to other anti-androgen. It offers mild side effects and blocks your testosterone and DHT fully. Bicalutamide has yet to become the standard antiandrogen of any country, even though it is offered in most. Side effects of Bicalutamide still exist, such as liver damage and the raising of liver enzymes. Liver function monitoring alongside your regular blood work, is recommended. However, one of Bicalutamide’s main drawbacks is the lack of clinical research that has been done on its use in transgender medicine. The use of Bicalutamide on cisgender people has been going on for the last 20 years, though.
The standard dosing of Bicalutamide is 50mg every day; when your levels get lower, the dosage can always get lower as well. Another big advantage of Bicalutamide is the half-life being 5.8 days ranging to 10 days if you are repeatedly taking the dosage. Meaning you can take Bicalutamide every other day or every 3 days and not have to worry about your testosterone not being blocked. Overall, Bicalutamide is a newer medication that has been gaining traction in use for transgender women. Compared with other medications, it offers fewer side effects while still maintaining the same if not better testosterone blockage.
Estrogen monotherapy – The use of only estrogens in your hormone regime has also been increasingly common as of the last couple of years. Estrogen itself is similar to Lupron, as both of them are GnRH modulators. However, one of the caveats of doing this method is that you have to take higher levels of estrogen to get adequate suppression of testosterone.
“There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more.”
You may have to take 6, 8, 10, or even 12mgs of estradiol to suppress your testosterone adequately. Depending on your doctor, they might not feel comfortable with you being on a higher dose of estrogen.
The advantages of doing monotherapy are the lack of side effects, and your overall hormone regime being less expensive. It may be a good idea for those who have higher testosterone to start on a blocker for a safety net. Then drop the blocker once your levels are good. On the condition that you and your doctor are comfortable with a higher estradiol range, you can have great results on estrogen monotherapy alone.
Finasteride – Finasteride was originally prescribed for men suffering from male pattern baldness. Finasteride itself fits into the category of 5α-reductase inhibitor or Dihydrotestosterone (DHT) blocker. DHT often causes male pattern baldness; blocking DHT will hopefully stop or reduce hairs from thinning or balding. In the case of transgender women, Finasteride is commonly prescribed but alone doesn’t block testosterone. For those who want their testosterone suppressed and not just DHT, Bicalutamide would be a good option as it does both.
Finasteride has seen less usage lately, one of the reasons being the long list of side effects when using the medication. To name a few, depression, suicidal ideation, and anxiety. Transgender women are already disproportionately affected by suicidality, depression, and anxiety. By prescribing medications with mental health risks, it can heavily increase their mental distress. Finasteride has a half-life of 6 hours, so dosing multiple times in a day is common. Dosing itself can range from 1mg on the lower end to 5mg on the higher.
Estrogen monotherapy testosterone suppression – https://www.liebertpub.com/doi/full/10.1089/trgh.2017.0035