Informational Resource for Transgender and Gender Diverse Adolescents and Their Families – Adolescent Gender Affirming Anti-Androgens

Information About Anti-Androgens

NOTE: This information is compiled from several sources readily available on the internet as identified below. This guidance manual is intended to be used for informational purposes only and is not a substitute for medical advice from a competent health care professional. While we hope this guidance manual is helpful; please consult a knowledgeable healthcare provider for medical advice, treatment, and additional informational based on specific health care needs and medical history.

What are anti-androgens?

The industry standard for blocking testosterone in bodies that make more of it (usually bodies with testicles) is leuprolide acetate. Leuprolide works in the body to reduce signals from the brain to the gonads (ovaries or testicles) which decreases sex steroid hormones (estrogen and testosterone) to pre-puberty levels. But leuprolide might be harder to source than oral medications that lessen the effects of testosterone, called anti-androgens. Oral anti-androgens only work to lessen the effects of testosterone, not estrogen. They don’t significantly decrease testosterone levels (some might even increase it), but they interfere with testosterone’s ability to interact with the body’s cells which prevents the testosterone from causing things like facial hair or a deeper voice. Anti-androgens may be a consideration for an individual if leuprolide is difficult to access.

(UCSF “Overview of feminizing hormone therapy”, Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen, and Fenway Health, “Medical Care of Gender Diverse Children and Adolescents.”).

What are the types of anti-androgens and how do they work?

Spironolactone is the most common anti-androgen medication, but dutasteride and bicalutamide have also been used.

Spironolactone is an oral medication that is used to treat high blood pressure, diabetes, acne, and unwanted body hair. It might slightly reduce testosterone production and more powerfully decreases its effects in the body.
Dutasteride is an oral medication that is used to treat prostate problems and unwanted hair loss on the head. It reduces testosterone effects in the body by reducing the conversion of testosterone to the more active form, dihydrotestosterone. It can actually cause an increase in testosterone levels in some people (1%).
Bicalutamide is an oral medication that is used to treat prostate cancer and unwanted hair loss on the head. It reduces testosterone effects in the body by reducing the binding of the more active form, dihydrotestosterone, to receptors. However, something to consider is that it can actually cause an increase in testosterone levels in some people but because it can’t bind to receptors the increased levels don’t cause any issues.

What are the side-effects or potential risks of using anti-androgen medications?

All oral anti-androgen medications have the potential to cause breast development even without taking estrogen. The breast tissue can be permanent, even if you stop the medication. They are also likely to decrease erection firmness and frequency, although less so then leuprolide.

Spironolactone makes you pee more often. Also, it isn’t safe to take if you have hyperkalemia (high potassium); Addison disease (adrenal insufficiency); or take a medication called eplerenone. Some trans people report feeling mentally foggy on spironolactone. Side effects are dose dependent (higher doses usually cause more side effects). Overall, this medication taken in conjunction with estradiol, is usually well tolerated and effective at the doses recommended by industry guidance (see page Estrogen of guidance manual for more information). Blood tests are needed if you have pre-existing health issues or if you take doses over 100mg a day. See Lab Guide for more information.
Dutasteride side effects are mainly sexual side effects. They can include fewer erections, less interest in sex, or changes in ejaculate. Although less common, it has been known to cause depression, so individuals may want to avoid it if they already struggle with depression. According to the standard of care, no baseline or monitoring labs are needed.
Bicalutamide has caused deaths in less than 1% of adult cis males who take it. It has been used safely in trans youth and young adult cis women. It can harm the liver, so individuals should avoid it if they have any known liver conditions, diabetes, high blood pressure, auto-immune conditions, take other medications that are tough on the liver, or are medically fragile in any way. Alcohol and tylenol (or acetaminophen) should be avoided while on bicalutamide.

What forms does it come in and how are they dosed?

NOTE: The information has been collected to create a comprehensive guide for individuals and health care professionals less familiar with these treatment regimens, but is NOT intended to be a substitute for medical advice from a doctor or other health care provider familiar with your particular case and medical history. Please take these medication as directed by a healthcare provider.

All of the following anti-androgens come as tablets which can usually be cut.

Spironolactone: Dosing starts at 25mg by mouth daily. 25mg daily for at least a week before increasing to 50mg daily. Individuals could increase by 25mg each week up to a total dose of no more than 100mg a day (UCSF “Overview of feminizing hormone therapy”, Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen, and Fenway Health, “Medical Care of Gender Diverse Children and Adolescents.”). Most individuals will need a dose of 50-100mg per day. If taken with estradiol, 50mg will work well for most individuals. Any dose of 100mg or less can be taken one time per day.
Dutasteride: The tablets are only available in 0.5mg doses. The recommended dose is one tablet by mouth daily. There is no alternative dosing.
Bicalutamide: Baseline bloodwork to measure liver enzymes called AST and ALT are HIGHLY recommended prior to starting. If the levels are higher than the expected range of the lab, do NOT start bicalutamide. Another blood draw to check AST and ALT are recommended after you’ve been on the medication for 4 weeks — if they are over the expected range of the lab, you should stop bicalutamide immediately and seek medical care. Take ½ of a 50mg tablet (to make 25mg) by mouth just twice per week. It has a long half-life (5.5 days) which means it stays in your system longer and you do not have to take it everyday for it to work. By decreasing the total dose exposure, this dosing makes the medication safer for your liver while still being equally effective. The doses in adults with prostate cancer that lead to death were 100mg or more, taken everyday. If 25mg twice a week is not effective enough, dose can be increased to 50mg (1 whole tablet) by mouth twice weekly. Doses higher than this are less safe and usually unnecessary for efficacy.
(UCSF “Overview of feminizing hormone therapy”, Seattle Children’s Gender Clinic, “A Guide to Gender Affirming Hormone Therapy with Estrogen, and Fenway Health, “Medical Care of Gender Diverse Children and Adolescents.”).

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