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Comparability of serum, plasma, and urinary estrogen and estrogen metabolite measurements by sex and menopausal status

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Abstract

Purpose

The comparability between serum, plasma, and urinary measurements of estrogen metabolites via liquid chromatography–tandem mass spectrometry (LC–MS/MS) has not been largely explored, and it is unclear if urinary LC–MS/MS measurements are suitable surrogates of circulating levels.

Methods

Serum, plasma (EDTA and heparin), and urinary estrogen/estrogen metabolite levels were measured via LC–MS/MS in paired samples from 64 healthy volunteers (18 men, 20 premenopausal women, 26 postmenopausal women). Geometric means and Spearman correlation coefficients were used to compare individual and combined pathway levels of estrogens/estrogen metabolites across biologic matrices by sex/menopausal status.

Results

Measured concentrations of estrogens/estrogen metabolites across blood matrices were almost identical (percent differences < 4.8%). Parent estrogen concentrations measured in serum and urine were moderately correlated in postmenopausal women (estrone: r = 0.69, estradiol: r = 0.69). Correlations were similar comparing unconjugated serum estradiol to urinary estrone (r = 0.76) and urinary estradiol (r = 0.65) in postmenopausal women but were moderate to low in premenopausal women (r = 0.60, 0.40, respectively)/men (r = 0.33, 0.53, respectively). Comparing metabolite ratios, proportionally higher concentrations of 16-pathway metabolites were measured in urine versus serum across sex/menopausal status groups (e.g., postmenopausal women: 50.3% 16-pathway metabolites/total in urine versus 35.3% in serum).

Conclusions

There is strong agreement between estrogen/estrogen metabolites measurements in serum, heparin plasma, and EDTA plasma. Individual estrogen metabolite concentrations were moderately correlated between urine and serum, but were not well correlated when evaluating pathway- or relative estrogen concentrations. Differences between serum and urine are likely explained by differences in metabolism and/or excretion.

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Funding

This work was supported by the Intramural Research Program of the National Cancer Institute.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA

    Sally B. Coburn, Roni T. Falk, Katherine A. McGlynn, Louise A. Brinton, Joshua Sampson & Britton Trabert

  2. Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Frank Z. Stanczyk

  3. Department of Laboratory Medicine, Harvard Medical School and Children’s Hospital, Boston, MA, USA

    Gary Bradwin

  4. Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    Xia Xu

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  1. Sally B. Coburn
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  2. Frank Z. Stanczyk
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  3. Roni T. Falk
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  4. Katherine A. McGlynn
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  9. Britton Trabert
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Correspondence to Britton Trabert.

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Coburn, S.B., Stanczyk, F.Z., Falk, R.T. et al. Comparability of serum, plasma, and urinary estrogen and estrogen metabolite measurements by sex and menopausal status. Cancer Causes Control 30, 75–86 (2019). https://doi.org/10.1007/s10552-018-1105-1

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  • DOI: https://doi.org/10.1007/s10552-018-1105-1

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