CONTEXT: Endocrine Society guidelines for dosing of feminizing gender-affirming hormone therapy (GAHT) have remained essentially unchanged since 2009. The Endocrine Society recommends periodic monitoring of serum estradiol levels, with the goal of maintaining levels in the premenopausal cisgender female range (100-200 pg/mL). However, it is not clear whether guideline-concordant dosing consistently produces guideline-recommended levels across common estradiol formulation types (oral pills, parenteral injections, transdermal patches). OBJECTIVE: All transgender and nonbinary patients receiving estradiol-based GAHT between October 2015 and March 2023 were reviewed at a single center, with the goal of determining the frequency with which guideline-concordant dosing with different estradiol formulations led to guideline-recommended estradiol levels. METHODS: Demographics, GAHT regimen, and estradiol levels were obtained via chart review, and data were analyzed descriptively. RESULTS: The analytic population included n = 35 individuals, including n = 9 prescribed oral estradiol pills, n = 11 prescribed parenteral injections, and n = 15 prescribed transdermal patches. With guideline-concordant doses of oral estradiol (mean 2.8 mg daily), the mean follow-up level was 168 pg/mL
32% of follow-up levels were subtherapeutic and 14% were supratherapeutic. With guideline-concordant doses of parenteral estradiol (mean 5.8 mg weekly), the mean midpoint follow-up level was 342 pg/mL
91% of midpoint follow-up levels were supratherapeutic. With guideline-concordant doses of transdermal estradiol (mean 0.09 mg/day), the mean follow-up level was 81.5 pg/mL
70% of follow-up levels were subtherapeutic. CONCLUSION: Supratherapeutic follow-up estradiol levels were common with guideline-concordant parenteral estradiol doses, as were subtherapeutic follow-up levels with guideline-concordant transdermal doses. These findings may suggest the need for revision of guideline-recommended estradiol doses for these formulations.