Our new endocrine clinic is monitoring estradiol levels in transgender male patients (female to male) and asked if our standard estradiol immunoassay is appropriate to use in this setting. What do you recommend?

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A. Using gender-affirming hormone therapies is increasingly common in transgender and nonbinary populations, and monitoring hormone concentrations may help provide optimal outcomes for these patients.

Testosterone hormone therapy may be used by patients who desire masculinizing effects. Estradiol (E2) concentrations are expected to decrease concurrently with use of testosterone hormone therapy. However, guidelines do not address specific ranges or preferred testing methods for hormone measurements in these patients.^1-3 The ideal concentrations will depend on the desired effects and vary by individual.

Overall, given sensitivity concerns, differences among testing platforms, and the possibility of immunoassay interference,⁴ liquid chromatography-mass spectrometry (LC-MS) methods are preferred when low E2 concentrations are expected. Low E2 concentrations may be expected in individuals desiring E2 concentrations below cisgender male reference intervals, prepubertal patients, and individuals using estrogen-suppressing therapy (e.g. testosterone or aromatase inhibitors). While there are notable differences between methods, if optimal gender-affirming effects are obtained at E2 concentrations above the cisgender male reference interval, immunoassay methods may provide results that are clinically comparable to those of LC-MS⁵ and, therefore, may suffice. However, LC-MS methods may be useful if immunoassay results do not align with the clinical situation or expected results.

1. Deutsch MB, ed. Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People. 2nd ed. University of California San Francisco Gender Affirming Health Program; 2016. transcare.ucsf.edu/guidelines
2. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869–3903.
3. Coleman E, Radix AE, Bouman WP, et al. Standards of care for the health of transgender and gender diverse people, version 8. Int J Transgend Health. 2022;23(suppl 1):S1–S259.
4. Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME. Challenges to the measurement of estradiol: an Endocrine Society position statement. J Clin Endocrinol Metab. 2013;98(4):1376–1387.
5. Greene DN, Schmidt RL, Winston-McPherson G, et al. Reproductive endocrinology reference intervals for transgender men on stable hormone therapy. J Appl Lab Med. 2021;6(1):41–50.

Joely Straseski, PhD, DABCC
Professor of Pathology
University of Utah School of Medicine
Section Chief, Clinical Chemistry
Medical Director, Endocrinology
ARUP Laboratories
Salt Lake City, Utah
Member, CAP Accuracy-Based Programs Committee

Brian Harry, MD, PhD
Assistant Professor of Pathology
University of Colorado Anschutz Medical Campus
Aurora, Colo.
Member, CAP Accuracy-Based Programs Committee