Injectable Estradiol Dosing Regimens in Transgender and Nonbinary Adults Listed as Male at Birth

Many transgender and nonbinary (TGNB) individuals assigned male at birth (AMAB) seek hormone therapy to achieve physical and emotional changes. Standard therapy includes estradiol, with or without an antiandrogen. Our clinical observations suggest that currently recommended injectable estradiol dosing may lead to supratherapeutic estradiol levels.

We sought to evaluate whether lower-than-recommended doses of injectable estradiol were effective in achieving serum estradiol and testosterone goals.

We conducted a retrospective cohort study to evaluate injectable estradiol dosing in treatment-naive AMAB individuals initiating hormone therapy. Data from a single provider at an academic center from January 2017 to March 2023 were analyzed. A total of 29 patients were eligible for inclusion. The primary variables of estradiol dosage, serum estradiol, and testosterone levels were analyzed over 15 months.

The average estradiol dose decreased from 4.3 to 3.7 mg weekly (P < .001) during the study period with a final on-treatment estradiol level of 248 pg/mL. All individuals achieved a testosterone level of less than 50 ng/dL during the study period. The average initial on-treatment testosterone level was not significantly different from average final on-treatment measurement of 24.0 mg/dL (P = .95). Spironolactone use at study initiation was not associated with a lower initial on-treatment testosterone level, though it was associated with a lower estradiol level of 285 pg/dL compared to 427 pg/dL for those on estradiol monotherapy (P = .017).

Lower doses of injectable estradiol can achieve therapeutic estradiol levels with excellent testosterone suppression. Spironolactone was not associated with additional testosterone suppression and may result in lower estradiol levels.