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 that was originally used to treat prostate cancer in men, as well as fluid build-up due to heart failure and kidney diseases. In the case of transgender women, it is used as an off label anti-androgen since it is a 5α-reductase inhibitor. A 5α-reductase inhibitor stops the binding of testosterone and the conversion of Dihydrotestosterone (DHT) in natal men. Since spiro is a potassium-sparing diuretic, when you are on this medication your body may have trouble absorbing sodium. It is very common for trans women to have salt cravings when on spiro. Spiro also has a common side effect of you needing to frequently use the bathroom.
Spiro is currently the most common and 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 higher doses of the medication, the side effects get much worse while the testosterone-blocking does not get much better. Common side effects are drowsiness, high potassium levels, headaches, and brain fog. Furthermore, since we use spiro as an off label medication for the side effect of blocking testosterone, some don’t have good results on it. For instance, I was on Spiro for the first 8 months of my transition and it did not properly block my testosterone, and other types of testosterone blockers worked better for me.
The half-life of spiro is about 12 hours, so for optimal results, you want to be dosing twice a day. Important note, if you are taking spiro you need to make sure you limit the amount of potassium that 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 it is not approved by the FDA (federal drug administration). Cyproterone acetate is unique in the fact that is also a progestin; progesterone is a common hormone in cis girl’s bodies and plays an important role in ovulation and pregnancy. The use of progestins in HRT treatment for transgender women is very common since high levels of progesterone tend to increase water weight and may make your breast look “fuller”.
Cyproterone acetate has a similar effect to a GnRH modulator. A GnRH modulator is a classification of medications that stimulate the LH (luteinizing hormone) and FSH (follicle-stimulating hormone). The LH and FSH in the case of natal men, are the signal to the testicles to produce hormones. If you shut down the signals then your body no longer produces high levels of testosterone, which in the case of transgender women is optimal.
Cyproterone acetate itself is a very powerful medication and can have unpleasant side effects. Such as depression, fatigue, high prolactin production, and problems associated with liver health. 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 a person taking Cyproterone acetate you need to be routinely checking for prolactin since Cyproterone acetate increases the production of prolactin. Higher levels of prolactin can cause prolactinoma which is 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 who are over the age of 18, you may have a hard time getting lupron covered by insurance. Not only that but to pay for the medication out of pocket it can be upwards of $1,700 USD for a kit.
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 for the first month, you may see the opposite of the changes that you might want, such as increased masculinization for trans girls or increased feminization for trans men. The reasoning for this is, 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. Lupron can be used for both trans men and trans women.
Dosing is almost always 3.5-7.5 mg per month, but the amount you take depends on when you want to dosage next. Side effects of Lupron 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 period of time without the supplementation of testosterone or estrogen, 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 blockers 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 the production of androgen receptors and the conversation of testosterone to dihydrotestosterone (DHT). One of the unique attributes of Bicalutamide is that your blood work will still show the levels of testosterone but in reality, 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 raised in popularity and usage in comparison with other anti-androgen since it has 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. It can be difficult for your insurance to cover it and paying for Bicalutamide out of pocket can be very expensive. 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 the main drawbacks of Bicalutamide is the lack of clinical research that has been done on its use in relation to transgender women. Use of Bicalutamide on cisgender people has been going on for the last 20 years though, it doesn’t seem like there are any reasons why transgender people shouldn’t use it.
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 that 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. In comparison with other medications, it offers fewer side effects while still maintaining the same if not better blocking of testosterone.
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. One of the cavotiouts of doing this method however, is that you have to take higher levels of estrogen to get adequate suppression of testosterone and not everyone may be able to do it.
“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.”
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. For those who have higher testosterone to start, it may be a good idea to start on a blocker for a safety net then get off of the blocker once your levels drop. On the condition that you and your doctor are both comfortable with a higher range of estradiol, you can have great results on just estrogen monotherapy.
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. Male pattern baldness is often caused by DHT so blocking the DHT will hopefully stop or reduce hairs from thinning or balding. In the case of transgender women, Finasteride is commonly prescribed but in of itself 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 been seeing less usage lately, one of the reasons for that being the long list of side effects that come with using the medication. To name a few, depression, suicidal ideation, and anxiety. Transgender women are already disproportionately affected by suicidality, depression, and anxiety; prescribing them a medication that can make that worse, might not be for the best. 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