Testosterone Blocker Options for Transgender Women

Transgender women are individuals who were assigned male at birth but who identify as women. Although not all transfeminine individuals have a desire to undergo a medical or surgical gender transition, many do.

Often, the first step in a medical gender transition is to begin hormone therapy, also known as gender-affirming hormone therapy. For transgender women, this involves not just the use of estrogen or estradiol but also the use of a testosterone blocker.

Hormones and Gender Presentation

In cisgender women and some transgender people, estrogen dominates the body from puberty onward. The presence of more estrogen than testosterone causes breast growth. It also makes the skin softer, and there are other more subtle changes as well.

In cisgender men and some transgender people, testosterone predominates. It causes changes in patterns of hair growth—including androgenic alopecia (more commonly known as male pattern baldness) and facial hair growth. It causes the shoulders to widen and Adam's apple to enlarge. It thickens the vocal cords, leading the voice to drop.

High levels of testosterone can also increase a person's sex drive or aggression.

Some of these hormone-driven differences are the goals of hormone therapy for transgender individuals. For transgender individuals, having a body that more closely matches their gender identity can decrease their dysphoria and lessen their chances of facing transphobic discrimination and violence. Hormone therapy can move them toward that goal.

Testosterone Blockers

Testosterone acts much more strongly than estrogen does.

Transmasculine People and Testosterone

When transmasculine people, those assigned female at birth who identify as men or as nonbinary, are given testosterone, they experience clear masculinizing changes. They grow facial hair, their voices deepen, and their faces may subtly reshape.

These testosterone-driven changes are generally irreversible. Once someone has facial hair, it needs to be removed by laser hair removal or electrolysis. Voice pitch can be deepened by testosterone but not raised by estrogen. The angles of the face can change slightly in trans men due to testosterone due to muscle changes and fat redistribution in the face which make it appear more angular.

Transfeminine People and Blockers

The fact that testosterone is more efficient at masculinizing someone than estrogen is at feminizing makes transitioning more difficult for transgender women. They can't just take estrogen to develop more feminine characteristics.

They must also reduce their natural testosterone. This can be done using either testosterone blockers or surgery to remove the testes (which produce testosterone). The two testosterone blockers most often used for transgender women are spironolactone (also known as "spiro") and cyproterone acetate.

Currently, cyproterone acetate is not used in the United States due to concerns about liver toxicity. However, it is widely used in Europe. Some transgender women who transition early using puberty blockers may remain on those blockers to suppress their testosterone once they start gender-affirming hormone therapy.

Leuprolide acetate is also sometimes used as a testosterone blocker. There are a variety of others as well.

Spironolactone

Spironolactone is the most commonly used anti-androgen in the United States. It is not just used as a testosterone blocker for transgender women, either. Spironolactone is also used to treat high blood pressure and heart failure.

Evidence suggests that spironolactone is a very safe way to lower testosterone activity. However, as spironolactone is a diuretic (water pill), using it as a testosterone blocker may cause some transgender women to urinate frequently.

Cyproterone Acetate

Cyproterone acetate is commonly used as a testosterone blocker for transgender women in Europe. Some research suggests that it is more effective at lowering testosterone levels than spironolactone. It may also improve breast growth for transgender women.

There is also some evidence that cyproterone acetate may cause other negative health consequences by decreasing HDL cholesterol and increasing amounts of the hormone known as prolactin (the hormone responsible for breast milk production).

Histrelin

Histrelin is a gonadotropin-releasing hormone (GnRH) agonist that is sometimes used as a puberty blocker for transgender youth. It is available in a number of forms, including an implant (supprelin) that lasts for up to one year. Because histrelin/supprelin is an effective way to reduce testosterone, it is sometimes continued as part of hormone therapy. (It can also be used to treat hormone-sensitive prostate cancers.)

Histrelin is less often used as a testosterone blocker for transgender adults who start to transition after puberty, but it is an option.

Progesterone

Some forms of progesterone have some testosterone-blocking effects. They are not routinely used in feminizing hormone treatments, as there is no proven benefit and possibly increased risk with their use. However, this is a controversial topic. Some transgender women report weight gain, improved breast development, libido, or mood with their use. However, others may experience depression.

Previous studies in cisgender women showed increased cardiovascular risk and breast cancer risk, but this may not apply to transgender women. There is no proven risk in transgender individuals, but this topic is also not well studied.

Occasionally progesterone medications are used as part of gender-affirming hormone therapy after an in-depth discussion with a healthcare provider. These medications include micronized progesterone (Prometrium) and oral medroxyprogesterone acetate (Provera).

Orchiectomy

Orchiectomy, or surgical removal of the testes, is a very effective way to reduce testosterone in the body. Unlike all the testosterone-blocking medications, it is permanent. Therefore, orchiectomy is usually not indicated until a person is very stable in their gender identity. It is sometimes done as part of vaginoplasty surgery, but many transgender women have no interest in this option.

Removing the testes allows transgender women to be effectively treated with much lower doses of estrogen than they would need otherwise. This can improve the safety of treatment for transgender women where estrogen treatment would otherwise be very high risk.

Guidelines for accessing orchiectomy as a gender-affirming surgery are similar to those for accessing vaginoplasty.

A Word From Verywell

Understanding how testosterone and estrogen operate in the body is helpful in order to make decisions about gender-affirming hormone therapy. Discussing these options with your healthcare provider is a great starting point if you are a transgender woman who is interested in hormonal therapy. Your healthcare provider should evaluate your medical history and health status, as well as discuss with you your best options for proceeding.