madman
Super Moderator
Background
Exogenous estradiol (E2) may be prescribed for transgender females and menopausal women. Automated E2 immunoassays are widely used but bias often exists when compared to mass spectrometry (LC-MS) methods. Lack of assay standardization may hinder E2 dose adjustment, particularly when adhering to assay-agnostic thresholds defined in clinical guidelines. The goal of this study was to characterize bias in a subset of commercially available E2 immunoassays as compared to a LC-MS method and evaluate whether the route of E2 administration affected results. This study also included a unique real-time comparison of 3 different assays offered by one vendor; both legacy and currently available formulations. This provided insight into changes in assay formulations and how patient results may be affected over time, which could change patient management and/or dosing strategies. The effect of estrone (E1) was determined and assay- and route-specific desirable thresholds were calculated to better guide clinical interpretation of results.
Methods
Plasma samples were obtained from 174 transgender female patients receiving exogenous E2 via transdermal, oral, or intramuscular (IM) routes. E2 was measured using five automated immunoassays from three vendors (Abbott, Beckman (E2 [‘BEC-E2-Legacy’], Sensitive Estradiol version 1 [‘BEC-SNSE2-v1’], Sensitive Estradiol version 2 [‘BEC-SNSE2-v2’]) and Roche; results were compared to E2 by LC-MS. E1 was measured using LC-MS.
Results
All immunoassay platforms showed bias relative to LC-MS. E1 concentrations were highest in patients receiving oral E2, which exhibited the largest magnitude of bias (negative in Abbott, BEC-SNSE2-v1, BEC-SNSE2-v2, and Roche; positive in BEC-E2-Legacy) with the Beckman assays most affected. Bias direction differed by route for BEC-SNSE2-v1, BEC-SNSE2-v2, and Roche. Compared to BEC-E2-Legacy, BEC-SNSE2-v2 improved in overall bias, however direction and magnitude of route-specific bias changed over time for the 3 Beckman assays. Assay-agnostic desirable thresholds of 100-200 pg/mL miscategorized 12-24% of patients, with the majority receiving oral E2. Assay-specific desirable ranges were similar across E2 routes for the Abbott and Roche assays but were markedly different across routes for the Beckman assays.
Conclusion
E2 immunoassays show bias relative to LC-MS and this bias differs by route of exogenous E2. Assay- and route-specific thresholds may be needed to monitor patients receiving exogenous E2. Clinicians should be aware of differences between methods and routes of administration, as both may impact result interpretation and subsequent treatment in these patient populations.
