Direct immunoassays shouldn’t be used to measure estrogens and their metabolites in patients with very low estrogen concentrations, according to a report published online April 7 in the Journal of Clinical Endocrinology and Metabolism.
“The inaccuracy of direct immunoassays is especially problematic in ... men, postmenopausal women, those taking aromatase inhibitors, and prepubertal children. Thus, the use of current direct assays for measuring estradiol concentrations in these groups of patients should be discouraged,” wrote Dr. Laurence Demers of the Pennsylvania State University, Hershey, and his associates.
Mass spectrometry has better sensitivity and specificity, but mass spectrometers are expensive, and assays to quantify estrogen metabolites are demanding. Because of that, many labs continue to use direct immunoassays even when they’re not the best choice.
The report summarized the consensus from a 2014 meeting of experts in Bethesda, MD., on the measurement of the estrogens and their metabolites. In general, participants agreed that measurements need to be standardized and improved (J. Clin. Endocrinol. Metab. 2015 April 7 [doi:10.1210/jc.2015-1040]).
“Assay inaccuracy complicates the comparison of results obtained from different laboratories, from the same laboratory over time, or from different epidemiological and clinical studies and constrains the application of guidelines to ... patients. A set of clinical practice guidelines cannot be implemented unless the assays used are accurate and precise,” according to the investigators.
Even so, “measurement of estradiol is challenging because the physiologically relevant concentration range spans at least four orders of magnitude ... an assay that is suitable for use for diagnosis and management of infertility in adult women may not meet performance specifications for use when evaluating the onset of puberty in a child,” they said.
Current estradiol assays are particularly problematic in postmenopausal women and children, where sensitivity is critical. Reference ranges haven’t been established for either group. The Centers for Disease Control and Prevention are working to address those and other problems under a Hormone Standardization Program.
Meanwhile, “use of currently available direct estradiol immunoassays appears to compromise assay specificity, probably due to antibody cross-reactivity, matrix effects, and suboptimal sensitivity. These direct assays usually yield higher values than [do] those measured by methods with superior specificity, including immunoassays preceded by organic solvent extraction, liquid chromatography, or gas or liquid chromatography mass spectrometry assays,” the authors said.
There’s a need “for a study to evaluate the different approaches for validation of estrogen assay accuracy. It [is also] recommended that journals require a statement regarding accuracy assessment for estrogen and estrogen metabolite assays with a long-term goal of requiring measurements using accurate assays,” they said.
The Bethesda meeting was sponsored primarily by the Endocrine Society, the American Association for Clinical Chemistry, and the Partnership for Accurate Testing of Hormones. One of the nine authors – Dr. Richard J. Santen of the University of Virginia, Charlottesville – has been a Pfizer adviser and is the principal investigator on a grant from the company to his university. The other authors have no disclosures.