Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States

Aaron L Misakian¹, Carly E Kelley², Erika A Sullivan³, Julia J Chang⁴, Gagandeep Singh⁵, Sarah Kokosa², Jonathan Avila⁶, Holly Cooper¹, Jane W Liang⁷, Bren Botzheim⁷, Meg Quint^{7

8}, Athavi Jeevananthan², Ellenor Chi⁹, Madison Harmer⁹, Laurel Hiatt¹⁰, Michaela Kowalewski⁹, Benjamin Steinberg⁹, Telisha Tausinga⁹, Hannah Tanner⁹, Tiffany F Ho³, Bayarmaa Mark⁹, Brian Zenger⁹, Sophia Hu¹¹, Amanuail Gebregzabheir^{12

13}, Justin M Penny⁵, Danielle F Loeb^{12

13

14}, Tyler Strickland^{12

13}, Sean J Iwamoto^{12

13

15}, Micol S Rothman^{12

13}, Ole-Petter R Hamnvik¹⁶, Danit Ariel⁴

Affiliations

¹ Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Stanford, CA 94304, USA.
² Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27710, USA.
³ Department of Family and Preventive Medicine, University of Utah, School of Medicine, Salt Lake City, UT 84108, USA.
⁴ Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA 94304, USA.
⁵ Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
⁶ Division of Adolescent Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA.
⁷ Stanford University School of Medicine, Stanford, CA 94304, USA.
⁸ Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
⁹ University of Utah, School of Medicine, Salt Lake City, UT 84108, USA.
¹⁰ Department of Human Genetics, University of Utah, School of Medicine, Salt Lake City, UT 84108, USA.
¹¹ Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹² Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
¹³ Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado School of Medicine Gender Diversity Programs: UCHealth Integrated Transgender Program, Aurora, CO 80045, USA.
¹⁴ Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁵ Endocrine Section, Medicine Service, Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA.
¹⁶ Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

PMID: 39797602
DOI: 10.1210/clinem/dgaf015

Multicenter Study

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States

Aaron L Misakian et al. J Clin Endocrinol Metab. 2025.

. 2025 Aug 7;110(9):e2898-e2907.

doi: 10.1210/clinem/dgaf015.

Authors

Affiliations

¹ Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Stanford, CA 94304, USA.
² Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27710, USA.
³ Department of Family and Preventive Medicine, University of Utah, School of Medicine, Salt Lake City, UT 84108, USA.
⁴ Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA 94304, USA.
⁵ Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
⁶ Division of Adolescent Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA.
⁷ Stanford University School of Medicine, Stanford, CA 94304, USA.
⁸ Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.
⁹ University of Utah, School of Medicine, Salt Lake City, UT 84108, USA.
¹⁰ Department of Human Genetics, University of Utah, School of Medicine, Salt Lake City, UT 84108, USA.
¹¹ Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹² Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
¹³ Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado School of Medicine Gender Diversity Programs: UCHealth Integrated Transgender Program, Aurora, CO 80045, USA.
¹⁴ Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁵ Endocrine Section, Medicine Service, Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA.
¹⁶ Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

PMID: 39797602
DOI: 10.1210/clinem/dgaf015

Abstract

Context: Guidelines for use of injectable estradiol esters (valerate [EV] and cypionate [EC]) among transgender and gender-diverse (TGD) individuals designated male at birth vary considerably, with many providers noting supraphysiologic serum estradiol concentrations based on current dosing recommendations.

Objectives: This work aimed to 1. determine the dose of injectable estradiol (subcutaneous [SC] and intramuscular [IM]) needed to reach guideline-recommended estradiol concentrations for TGD adults using EC/EV; 2. describe the relationship between estradiol concentration relative to timing/dose of last estradiol injection and other covariates; and 3. determine dosing differences between IM/SC EV/EC.

Methods: A cross-sectional retrospective study was conducted across 6 US medical centers including TGD adults on same-dose injectable estradiol for more than 75 days, with confirmed timing of estradiol concentration relative to last injection, from January 1, 2019 to December 31, 2023. Descriptive statistics were used to describe patient characteristics and weighted linear mixed models to evaluate relationship between various covariates and estradiol concentration.

Results: Data from 562 patients were included. Among those injecting every 7 days who reached the guideline-recommended estradiol concentration (n = 131, 27.5%), the median estradiol dose was 4.0 mg (interquartile range, 3.0-5.0 mg). Among all patients, the majority reached supraphysiologic estradiol concentrations (>200 pg/mL [>734 pmol/L]) while dose and timing in the injection cycle were significant covariates for the estradiol concentration. There were no significant dosing differences between IM/SC EV/EC.

Conclusion: Injectable estradiol esters effectively reach guideline-recommended estradiol concentrations but at lower doses than previously recommended. Estradiol concentrations are best interpreted relative to timing of last injection. Route of administration and type of ester do not significantly affect estradiol concentrations.

Keywords: estradiol cypionate; estradiol injections; estradiol valerate; gender-affirming hormone therapy; transgender.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.

PubMed Disclaimer

Comment in

Comments on Injectable Estradiol Use in Transgender and Gender-Diverse Individuals in the U.S.
Milano C, Harper J. Milano C, et al. J Clin Endocrinol Metab. 2025 Feb 27:dgaf134. doi: 10.1210/clinem/dgaf134. Online ahead of print. J Clin Endocrinol Metab. 2025. PMID: 40036325 No abstract available.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States

Affiliations

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States

Authors

Affiliations

Abstract

Comment in

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources