A paper in the January 2004 issue of Clinical Chemistry entitled “Immunoassay of estradiol: Unanticipated suppression by unconjugated estriol,” by Z Cao and coauthors of the New York State Department of Health, raises some important concerns about serum estradiol tests, especially in patients receiving estriol. Estriol is used alone or in combination with other estrogens for treatment of menopause, and is also being used experimentally in the treatment of multiple sclerosis.
When initial estradiol concentrations were low (200 ng/L), added estriol suppressed estradiol concentrations, resulting in falsely low concentrations. Different assay methods showed widely varying degrees of cross-reactivity.
Immunoassays, which are used for most serum hormone tests, have the advantages of very high sensitivity and relatively low cost. Virtually all methods are susceptible to some degree of interference and cross-reactivity, and recent research has highlighted these problems with respect to serum hormones.
Because this was an in vitro study, the implications for actual patient specimens are currently unknown. The fact that different immunoassays showed large differences in cross-reactivity suggests that practitioners will be best served by sticking with one assay methodology for serum estradiol, and appreciating that values from different laboratories may vary. Alternatively, estradiol, estriol, and estrone can be measured in urine by GC-MS, which is less susceptible to cross-reactivity. We will keep you posted as more data emerge.
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