Sublingual Estradiol Is Associated with Higher Estrone Concentrations than Transdermal or Injectable Preparations in Transgender Women and Gender Nonbinary Adults.

Serum hormone profiles among different feminizing gender-affirming hormone therapies (GAHT) are poorly characterized. To address this gap, we described the serum estrogen profiles of three 17β-estradiol preparations, taken with or without an antiandrogen, using a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay in adults taking feminizing GAHT. This was a secondary analysis of 93 healthy transgender women and gender nonbinary adults taking feminizing GAHT in a prospective cross-sectional study. Eligible participants took 17β-estradiol (sublingual tablet, transdermal patch, or intramuscular/subcutaneous injection) with or without oral spironolactone for ≥12 months before study entry. We determined serum estrone and estradiol concentrations for each hormone preparation and described the association between estrone and (1) clinically relevant estradiol concentration ranges (≤200 and >200 pg/mL) and (2) antiandrogen use. To achieve our objectives, we described our protocol for developing an LC-MS/MS assay to measure estrone and estradiol concentrations. Estrone concentrations were higher among participants taking sublingual 17β-estradiol tablets compared with transdermal or injectable preparations ( < 0.0001). Estradiol concentrations were higher for injectable versus transdermal preparations ( = 0.0201), but both were similar to sublingual tablet concentrations ( > 0.05). Estradiol >200 pg/mL (vs. ≤200 pg/mL) was associated with higher estrone concentrations among participants taking sublingual 17β-estradiol, but not transdermal or injectable 17β-estradiol. We observed no association between spironolactone and estrone concentrations ( > 0.5). Estrone concentrations were higher among transgender women and gender nonbinary adults taking sublingual 17β-estradiol compared with transdermal or injectable preparations. The role of estrone in clinical monitoring and the influence of other antiandrogens (e.g., cyproterone acetate) on the estrogen profile remain to be determined.