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

Maralee Kanin; Margaret Slack; Reema Patel; Kuan-Ting Chen; Nicholas Jackson; Kristen C Williams; Shira Grock

doi:10.1210/jendso/bvaf004

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

J Endocr Soc. 2025 Jan 21;9(5):bvaf004. doi: 10.1210/jendso/bvaf004. eCollection 2025 May.

Authors

Maralee Kanin¹, Margaret Slack², Reema Patel³, Kuan-Ting Chen⁴, Nicholas Jackson⁴, Kristen C Williams⁵, Shira Grock¹

Affiliations

¹ Division of Endocrinology, Diabetes & Metabolism, University of California, Los Angeles, 10833 Le Conte Ave, 57-145 CHS, Los Angeles, CA 90095, USA.
² Department of Medicine, Internal Medicine Residency, University of California, Los Angeles, 757 Westwood Plaza, Suite #7236, Los Angeles, CA 90095, USA.
³ Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
⁴ Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, 911 Broxton Ave, 3rd floor, Los Angeles, CA 90095, USA.
⁵ Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue Box 951738, Los Angeles, CA 90095, USA.

Abstract

Context: 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.

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

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: estradiol ranges; injectable estradiol; transgender women.