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

Area of Science:

• Endocrinology
• Gender-affirming care

Background:

• Transgender and nonbinary (TGNB) individuals assigned male at birth (AMAB) often pursue hormone therapy for physical and emotional transition.
• Standard hormone therapy typically involves estradiol, sometimes with an antiandrogen.
• Clinical observations suggest current injectable estradiol dosing protocols may result in excessively high estradiol levels.

Purpose of the Study:

• To assess if reduced doses of injectable estradiol can effectively achieve target serum estradiol and testosterone levels in TGNB individuals AMAB.
• To evaluate the efficacy of lower-dose injectable estradiol in hormone therapy.

Main Methods:

• Retrospective cohort study analyzing data from treatment-naive AMAB individuals initiating hormone therapy.
• Data collected from a single academic center between January 2017 and March 2023.
• Included 29 patients, analyzing estradiol dosage, serum estradiol, and testosterone levels over 15 months.

Main Results:

• Average weekly estradiol dose decreased from 4.3 to 3.7 mg (P < .001), with a final estradiol level of 248 pg/mL.
• All patients achieved testosterone levels below 50 ng/dL.
• Spironolactone use was linked to lower estradiol levels (285 pg/mL vs. 427 pg/mL) but not additional testosterone suppression.

Conclusions:

• Lower doses of injectable estradiol are effective for achieving therapeutic estradiol levels and suppressing testosterone in TGNB individuals AMAB.
• Spironolactone may not offer additional testosterone suppression benefits and could lower estradiol levels.
• Optimized injectable estradiol dosing warrants further investigation for safe and effective gender-affirming hormone therapy.