Challenges to the measurement of estradiol: an Endocrine Society Position Statement
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OBJECTIVE: The objective of the study was to evaluate the current state of clinical assays for estradiol in the context of their applications. PARTICIPANTS: The participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. EVIDENCE: Data were gathered from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), and the clinical and laboratory experience of the participants. CONSENSUS PROCESS: The statement was an effort of the committee and was reviewed by each member. The Clinical Affairs Committee, the Council of The Endocrine Society, and JCEM reviewers reviewed the manuscript and made recommendations. CONCLUSIONS: The measurement of estradiol in biological fluids is important in human biology from cradle to grave. In addition to its centrality in sexual development, it has significant effects on skin, blood vessels, bone, muscle, coagulation, hepatic cells, adipose tissue, the kidney, the gastrointestinal tract, brain, lung, and pancreas. Alterations in its plasma concentration have been implicated in coronary artery disease, stroke, and breast cancer. Although modern immunoassays and liquid chromatography/tandem mass spectrometry-based methods for estradiol are reasonably well suited to the diagnosis and management of infertility (nonetheless, imprecision and method-to-method differences remain problematic), the very low concentrations that appear to be crucial in nonreproductive tissues are a separate and more difficult issue. Such levels of estradiol are too low to be routinely measured accurately or precisely, and further evolution of analytical methods and the way in which estradiol is standardized is needed.
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Clinicians are increasingly using newer liquid chromatography-mass spectrometric-based assays with suggested improved sensitivity and reduced interference, particularly for steroids such as estradiol and testosterone, and for thyroid and peptide hormones.
“Clinicians are increasingly using newer liquid chromatography-mass spectrometric-based assays with suggested improved sensitivity and reduced interference.This is particularly true for steroids, namely E2, T (104,105), and thyroid and peptide hormones (78,106).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [106]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredFor clinical and sports applications, testosterone must be measured by LC-MS rather than immunoassays.
“A reliable threshold for circulating testosterone must be set using measurement by the reference method of liquid chromatography–mass spectrometry (LC-MS) rather than using one of the various available commercial testosterone immunoassays.”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [21]
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- Authors
- Rosner, W., Hankinson, S. E., Sluss, P. M., Vesper, H. W., & Wierman, M. E.
- Affiliations
- St. Luke's-Roosevelt Hospital Center (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Centers for Disease Control and Prevention (US)
- Denver VA Medical Center (US)
- Corresponding author
- Rosner, William
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-04-01
- Volume
- 98
- Issue
- 4
- Pages
- 1376-1387
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3615207
- OpenAlex
- W1987499470
- Semantic Scholar
- 06a4a976384d5fa73c1a86819a1cbc80f68f6293
- Cited by
- 408
- References
- 90
- Citations by year
- 2026: 30 · 2025: 36 · 2024: 34 · 2023: 29 · 2022: 33 · 2021: 14 · 2020: 46 · 2019: 23 · 2018: 25 · 2017: 33 · 2016: 28 · 2015: 34 · 2014: 27 · 2013: 16
- FWCI
- 24.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca049449-18, R01 CA49449, R01 CA49449 and)
- National Cancer Institute (R01-CA49449, R01‐CA049449, R01 CA6762)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Scientific Measurement and Uncertainty Evaluation
- Keywords
- estradiol measurement, liquid chromatography-tandem mass spectrometry, assay imprecision, low-dose estradiol, infertility diagnosis, plasma estradiol, biological fluids
- MeSH terms
- Diagnostic Techniques, Endocrine, Diagnostic Errors, Endocrinology, Estradiol, Humans, Professional Practice, Research Design, Societies, Medical, Practice Guidelines as Topic
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