Beckman Coulter Access Sensitive Estradiol test, subject of FDA adverse event reports, may give falsely low readings for trans women on oral HRT

Zinnia JonesHRT for trans women and transfeminine people is intended to lower testosterone levels and raise estrogen levels to those typically seen in cis women, which is confirmed through observed clinical effects and laboratory measurement of hormone levels. Guidelines such as those offered by the Endocrine Society recommend monitoring hormone levels at least annually, maintaining estradiol levels between 100-200 pg/mL and testosterone below 50 ng/dL (Hembree et al., 2017).

Estradiol, taken via different routes such as oral or sublingual tablets, transdermal patches, gel, or intramuscular injections, can differ in how it is metabolized and how effectively it raises estradiol levels. This is reflected in studies of estrogen levels in trans women taking various types of estradiol: transdermal patches may produce lower levels than tablets or injections, while tablets taken either orally or sublingually produce far higher levels of the metabolite estrone than patches or injections.

While all of these methods can effectively raise estradiol levels to the desired range, the state of high estrone levels now appears to interfere with the accurate measurement of estradiol by a specific brand of blood test, and this has been documented as producing inaccurately low readings of estradiol in trans women on HRT. Cirrincione et al. (2022) report on a recently discovered issue with the Access Sensitive Estradiol assay by Beckman Coulter:

On April 7, 2021, a manufacturer issued an important product notice alerting customers that a widely used estradiol immunoassay was not indicated for people undergoing exogenous estradiol treatment (Access Sensitive Estradiol, Beckman Coulter, Brea, CA, USA). A related US Food and Drug Administration Medical Device Report documented an occurrence of low measured estradiol concentrations in a patient undergoing exogenous estradiol treatment during an ovarian stimulation protocol (6). Further discussion with the vendor indicated that supraphysiologic circulating estrone concentrations, a metabolite of exogenous estradiol treatment (7, 8), may interfere with estradiol detection (Beckman Coulter Incorporated, personal communication).

To measure the extent and potential impact of these low readings on trans women taking HRT, the authors analyzed samples from 89 trans women on the Beckman Coulter test in question along with BC’s older estradiol assay, a Roche assay, and a control LC-MS/MS. Compared to the control, BC’s current test produced median readings of estradiol levels that were 34% lower, with the Roche test returning results a median of 12% lower and the older BC test reporting levels 17% higher. The current BC estradiol assay showed the greatest bias among trans women taking estradiol in tablet form, with median reported readings 40% lower than the control for tablets compared to 22% lower for patches and 10% lower for injections. The authors confirmed that this bias toward lower readings is influenced by the higher levels of estrone from oral HRT:

When considering the influence of estrone concentrations, the magnitude of bias in measured estradiol concentrations appeared to increase as estrone concentrations increased (Figure 1D) but was constant when estrone concentration was plotted relative to estradiol concentration (estrone/estradiol ratio) (Figure 2A).

As the manufacturer states in their April 2021 product notice, the Access Sensitive Estradiol assay should not be used for those taking estradiol as a medication, such as trans women on HRT: “Access Sensitive Estradiol test results may be either falsely increased or falsely decreased if they are measured after a patient receives estradiol supplements. … Do not use the Access Sensitive Estradiol assay to monitor the effectiveness of estradiol supplements.” Inaccurately low readings can have clinical consequences for trans women on HRT: dosage may be inappropriately adjusted upward from a normal range, causing a greater risk of adverse effects without achieving any greater feminization; conversely, dosage may not be appropriately adjusted downward if very high levels of estradiol go undetected. Cirrincione et al. note that among the population of trans women studied, inappropriate use of the Access Sensitive Estradiol assay over other tests could lead to different treatment decisions:

Using the New BC assay, we observed nearly half of participants in the >300 pg/mL concentration group (determined by LC-MS/MS) shifted to the 70-300 pg/mL estradiol concentration range (7 of 15 participants). Because the Endocrine Society and WPATH recommended monitoring estradiol concentrations to detect “supraphysiologic” concentrations during feminizing hormone therapy, clinicians may dose-decrease estradiol treatment in response to high estradiol measures. Our findings suggest care providers using the New BC assay may not detect clinically actionable estradiol concentrations, specifically measures that warrant dose-decreased estradiol treatment.

The FDA’s MAUDE database of medical device reports contains a number of adverse event reports related to BC’s Access Sensitive Estradiol test, with one 2020 entry stating that 10 patients taking estradiol valerate tablets were affected by inaccurately low reported estradiol levels. Trans women and transfeminine people on oral estradiol and receiving regular blood tests should be aware of the need for providers to use estradiol assays other than the Beckman Coulter Access Sensitive Estradiol test.

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About Zinnia Jones

My work focuses on insights to be found across transgender sociology, public health, psychiatry, history of medicine, cognitive science, the social processes of science, transgender feminism, and human rights, taking an analytic approach that intersects these many perspectives and is guided by the lived experiences of transgender people. I live in Orlando with my family, and work mainly in technical writing.
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