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Oestrogen during transition

Oestrogen is administered in gender care to trans women and some non-binary people who wish for feminising effects. It is used in supra-physiological doses — not to top up a deficiency, but to suppress a healthy male hormone system and replace it with a female one. That has a wide range of physical and cardiovascular consequences, with lifelong dependence on medication as the rule.

Types of oestrogen and routes of administration

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

• Tablets: simple, but because of the first-pass effect in the liver the highest thrombosis risk.
• Gel or spray: transdermal, more favourable thrombosis profile.
• Patches: stable release, lowest thrombosis risk.
• Injections: peaks and troughs in blood levels; less common in the Netherlands.

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

Effects

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

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

Anti-androgens

Oestrogen alone insufficiently suppresses testosterone production. In the Netherlands, cyproterone acetate or bicalutamide is usually added. Both have their own risk profiles:

• Cyproterone acetate: with long-term use associated with meningioma (a benign brain tumour). European medicines authorities have issued warnings about this; lower doses and shorter use are recommended.
• Bicalutamide: hepatotoxicity (liver burden) is a concern.
• Spironolactone: common elsewhere, affects electrolyte balance and kidney function.

After orchidectomy the need for anti-androgens disappears.

Medical monitoring

Regular check-ups are indispensable: hormone levels, liver function, prolactin, lipids, blood pressure and coagulation. Thrombosis risk is elevated, particularly in smokers, people with overweight, and with oral administration. With signs of thrombosis (swelling, pain in a leg, shortness of breath), immediate medical assessment is needed.

Long-term risks

Long-term oestrogen use in trans women is associated with a possibly increased risk of breast cancer (comparable to post-menopausal HRT), cardiovascular morbidity and possible consequences for bone density upon discontinuation without gonads. Long-term studies (>20 years) are scarce; many safety statements are extrapolated from non-trans populations.

Fertility

Oestrogen suppresses sperm production. With long-term use this can be irreversible, also after stopping. Cryopreservation of sperm before starting is strongly advised. See fertility and transition.