What is the most appropriate estrogen (oestrogen) to use in transgender patients?

From the Guidelines

For transgender patients seeking feminizing hormone therapy, transdermal 17-beta estradiol is generally considered the best estrogen option due to its better safety profile and more beneficial effects on circulating lipids, markers of inflammation, and blood pressure. This is based on the most recent evidence from 1, which suggests that transdermal administration of 17βE mimics physiological serum estradiol concentrations, avoiding the hepatic first pass effect and minimizing the impact of estrogens on the synthesis of hemostatic factors.

The dosing of transdermal 17-beta estradiol can vary, but a common range is 50-100 micrograms daily 1. Oral administration of 17-beta estradiol is also an option, with doses ranging from 1-2 mg daily 1, but it may have a higher risk of thromboembolic events due to the first-pass liver effect. Injectable forms of estradiol, such as estradiol valerate, can provide more stable hormone levels but require regular injections.

It is essential to avoid ethinyl estradiol (found in many birth control pills) due to higher risks of blood clots and cardiovascular events, as well as conjugated equine estrogens (Premarin) due to difficulty in measuring blood levels and potentially higher thrombotic risk. The estrogen therapy is typically combined with an anti-androgen such as spironolactone (100-300mg daily) or GnRH agonists to suppress testosterone production, as noted in 1. Regular monitoring of estradiol and testosterone levels is crucial, aiming for estradiol levels in the physiologic female range (100-200 pg/mL) and testosterone suppression below 50 ng/dL.

Key considerations for feminizing hormone therapy include:

• Starting with low doses and gradually increasing based on clinical response and hormone levels
• Preferring transdermal patches for patients over 40 or those with risk factors for thromboembolism
• Avoiding ethinyl estradiol and conjugated equine estrogens due to higher risks of thromboembolic events and difficulty in measuring blood levels
• Combining estrogen therapy with anti-androgens to suppress testosterone production
• Regular monitoring of estradiol and testosterone levels to ensure optimal hormone levels and minimize risks.

From the Research

Oestrogen Options for Transgender Patients

• The most effective oestrogen regimen for transgender women is still a topic of debate, with various studies suggesting different approaches 2, 3, 4.
• Transdermal 17-beta estradiol has been shown to result in more rapid suppression of total testosterone, lower estrone levels, and no differences in estradiol levels compared to sublingual estradiol 2.
• Oral estradiol therapy can be effective in achieving desired serum levels of 17-β estradiol, but there is wide individual variability in the amount required, and it may not always achieve adequate testosterone suppression 3.
• The use of spironolactone as an antiandrogen has been associated with impairment of obtaining desired 17-β estradiol levels, and finasteride has been linked to higher testosterone levels 3.

Comparison of Oestrogen Regimens

• A study comparing different GAHT regimens found that continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to sublingual estradiol 2.
• Another study suggested that oral estradiol alone may not be sufficient to achieve adequate testosterone suppression, and that additional testosterone-blocking treatment may be necessary 3.
• The optimal feminizing hormone treatment for transgender women is a topic of ongoing research, with various guidelines and strategies available 4, 5.

Considerations for Oestrogen Therapy

• Monitoring of hormone levels is crucial to individualize therapy and ensure that treatment goals are achieved 3, 4.
• The health risks associated with certain antiandrogen treatments, such as cyproterone acetate, are debated, and randomized protocols with other antiandrogen treatments are needed 4.
• Natural progesterone is not currently recommended as part of GAHT due to limited knowledge on the balance between risks and benefits 4.