Assay reproducibility and interindividual variation for 15 serum estrogens and estrogen metabolites measured by liquid Chromatography–Tandem mass spectrometry
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BACKGROUND: Interindividual differences in estrogen metabolism may partially account for differences in risks of estrogen-responsive cancers. We conducted a proof-of-performance study to assess the reproducibility of a LC/MS-MS method for measurement of 15 serum estrogens and metabolites (all 15 termed EM) in total (conjugated+unconjugated) and unconjugated forms and describe interindividual variation. METHODS: Interindividual variation in serum EM profiles was evaluated for 20 premenopausal women, 15 postmenopausal women, and 10 men. Replicate aliquots from 10 premenopausal women, 5 postmenopausal women, and 5 men were assayed eight times over 4 weeks. Components of variance were used to calculate coefficients of variation (CV) and intraclass correlation coefficients (ICC). RESULTS: In postmenopausal women and men, median EM concentrations were similar and substantially lower than that in premenopausal women. Within each sex/menopausal group, the sum of all EM varied 5- to 7-fold across extreme deciles. Some EM had greater variation; total estrone varied approximately 12-fold in premenopausal and postmenopausal women. Unconjugated estradiol varied 17-fold in postmenopausal women but only 5-fold in premenopausal women and men. CVs reflecting variation across replicate measures for individuals were <5% for most EM, but higher in some individuals with a low EM concentration. Overall laboratory CVs for all but one EM were <2% and ICCs were >99% for all EM in each group. CONCLUSIONS: The serum EM assay has excellent laboratory reproducibility. In premenopausal women, postmenopausal women, and men, interindividual variation in EM measures is substantially greater than laboratory variation. IMPACT: The serum EM assay is suitable for epidemiologic application. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."
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Circulating levels of estrogens vary greatly during the course of the menstrual cycle and decrease significantly in postmenopausal women.
“Circulating levels of estrogens vary greatly during the course of the menstrual cycle and decrease significantly in postmenopausal women (Table 3) [[306], [307], [308]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [308]
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References 20 · Cited by 36
- Authors
- Fuhrman, B. J., Xu, X., Falk, R. T., Dallal, C. M., Veenstra, T. D., Keefer, L. K., Graubard, B. I., Brinton, L. A., Ziegler, R. G., & Gierach, G. L.
- Affiliations
- National Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Fuhrman, Barbara J.
- ORCID
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2014-12-01
- Volume
- 23
- Issue
- 12
- Pages
- 2649-2657
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- PMC
- PMC4289148
- OpenAlex
- W2060348140
- Cited by
- 36
- References
- 20
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 6
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
- Funders
- Leidos
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (HHSN261200800001E))
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- serum estrogen, estrogen metabolites, assay reproducibility, interindividual variability, estrone, estradiol glucuronide, estradiol sulfate
- MeSH terms
- Chromatography, Liquid, Estrogens, Female, Humans, Male, Reproducibility of Results, Premenopause, Postmenopause, Tandem Mass Spectrometry
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