What are safe serum estradiol (E2) levels for transgender (trans) females?

From the Guidelines

For transgender females, safe estradiol levels typically range between 100-200 pg/mL (367-734 pmol/L), which mimics the levels found in cisgender women during their reproductive years. This target range is generally recommended for hormone therapy, though individual needs may vary based on health factors and transition goals 1. Common medications include oral estradiol, estradiol valerate injections, or transdermal estradiol patches, often combined with anti-androgens like spironolactone or cyproterone acetate to suppress testosterone production.

Key Considerations

• The optimal oestradiol doses or concentrations required to induce feminisation are unclear, but most individuals achieve oestradiol and testosterone concentrations in the cisgender female reference range 1.
• Feminising hormone therapy induces changes in body composition, breast growth, and other physical characteristics, but may also increase the risk of venous thromboembolism, weight gain, and cardiovascular disease 1.
• Regular blood tests every 3-6 months are essential to monitor hormone levels and adjust dosages accordingly.
• Potential side effects include blood clots, cardiovascular issues, and liver problems, making medical supervision crucial.
• Levels above 300 pg/mL generally don't provide additional feminization benefits but may increase health risks.

Treatment Goals

• The goal of hormone therapy is to achieve desired physical changes while maintaining overall health and minimizing risks.
• Healthcare providers should be knowledgeable and have sufficient training to provide safe and effective hormone regimens targeting the typical hormone ranges associated with the patient's gender identity 1.
• All patients seeking gender-affirming medical treatment should receive information and counseling for fertility preservation 1.

From the FDA Drug Label

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms.

The FDA drug label does not answer the question.

From the Research

Estradiol Levels for Trans Females

• The goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone 2.
• A study comparing different GAHT regimens found that transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, with most transgender women achieving cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches 2.
• The study also found that continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol 2.
• Another study found that cyproterone acetate had a higher testosterone suppression efficacy than spironolactone in feminizing hormone therapy for transgender women 3.
• A retrospective cross-sectional study found that the cyproterone group had significantly lower total testosterone concentrations compared with the spironolactone group and oestradiol alone group, and achieved serum total testosterone concentrations in the female reference range 4.

Safe Estradiol Levels

• The optimal estradiol level for transgender women is not well established, but a study suggests that a dose of 1 or 2 0.1 mg/24 hours estradiol patches can achieve cisgender women testosterone levels within 2 months 2.
• The study also found that there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group, suggesting that pulsed 17-beta estradiol likely provides no benefit for testosterone suppression 2.
• Another study found that cyproterone acetate had a higher testosterone suppression efficacy than spironolactone, but also had serious adverse effects such as drug-induced liver injury and asymptomatic hyperprolactinemia 3.

Comparison of Anti-Androgens

• A study compared the anti-androgenic effects of cyproterone acetate and spironolactone in transgender women, and found that cyproterone acetate had a higher testosterone suppression efficacy than spironolactone 3.
• Another study found that the cyproterone group had significantly lower total testosterone concentrations compared with the spironolactone group and oestradiol alone group 4.
• A review of antiandrogen treatment for acne found that combinations of cyproterone acetate and ethinyl estradiol had strong anti-acne activity, but that spironolactone and flutamide could not be endorsed based on current knowledge 5.