Estrogen in Gender Transition

Estrogen is administered in gender-affirming care to trans women and some non-binary people who desire feminizing effects. It is used in supraphysiological doses—not to correct a deficiency, but to suppress a healthy male hormonal system and replace it with a female one. This has a wide range of physical and cardiovascular consequences, with lifelong dependence on medication as the rule.

Types of estrogen and methods of administration

In transgender medicine, estradiol is used primarily (the physiological form), in ester form such as estradiol valerate, or as a synthetic alternative. Methods of administration:

• Tablets: simple to use, but due to the first-pass effect in the liver, they carry the highest risk of thrombosis.
• Gel or spray: transdermal, with a more favorable thrombosis risk profile.
• Patches: stable delivery and the lowest risk of thrombosis.
• Injections: peaks and troughs in blood levels; less common in the Netherlands.

Transdermal administration is clearly preferred over oral administration, precisely because the risk of thrombosis is considerably lower.

Effects

• Breast growth (variable, often more limited than expected and permanent).
• Softening of the skin and redistribution of fat toward the hips and buttocks.
• Reduction in muscle mass, muscle strength and athletic performance.
• Loss of erections and sperm production, often permanent.
• Only partial reduction of body and facial hair—for an adequate effect, electrolysis or laser treatment is needed.

The voice, height, shoulder width, hands, feet and facial skeleton do not change. Voice training or voice surgery is needed to change the voice.

Anti-androgens

Estrogen alone does not sufficiently suppress testosterone production. In the Netherlands, cyproterone acetate or bicalutamide is usually added. Both have their own risk profiles:

• Cyproterone acetate: associated with meningioma (a benign brain tumor) when used long term. European medicines authorities have issued warnings about this; lower doses and shorter treatment periods are recommended.
• Bicalutamide: hepatotoxicity (liver damage) is a concern.
• Spironolactone: commonly used elsewhere; affects electrolyte balance and kidney function.

After orchiectomy, anti-androgens are no longer necessary. Progesterone is also sometimes added, although evidence for its effectiveness is limited.

Medical monitoring

Regular checkups are essential: hormone levels, liver function, prolactin, lipids, blood pressure and blood clotting. The risk of thrombosis is increased, particularly in smokers, people who are overweight and with oral administration. In the event of symptoms of thrombosis (swelling, pain in a leg, shortness of breath), immediate medical examination is required.

Long-term risks

Long-term estrogen use in trans women has been associated with a potentially increased risk of breast cancer (comparable to postmenopausal HRT), cardiovascular morbidity and possible consequences for bone density if treatment is stopped without gonads. Long-term studies (>20 years) are scarce; many statements about safety are extrapolations from non-trans populations. See also cancer risk with hormone therapy and cardiovascular disease in gender transition. The effects of the hormone are described on transwijzer.nl.

Fertility

Estrogen suppresses sperm production. With long-term use, this may be irreversible, even after stopping treatment. Cryopreservation of sperm before starting treatment is strongly recommended. See fertility and gender transition.