Cancer Causes & Control

, Volume 30, Issue 1, pp 75–86 | Cite as

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

  • Sally B. Coburn
  • Frank Z. Stanczyk
  • Roni T. Falk
  • Katherine A. McGlynn
  • Louise A. Brinton
  • Joshua Sampson
  • Gary Bradwin
  • Xia Xu
  • Britton TrabertEmail author
Original paper



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.


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.


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).


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.


Estrogens Estrogen metabolites Urine Serum Plasma Comparison 



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

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflicts of interest.

Supplementary material

10552_2018_1105_MOESM1_ESM.docx (12 kb)
Supplementary Table 1 (DOCX 12 KB)


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Copyright information

© This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2018

Authors and Affiliations

  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, NIH, DHHSBethesdaUSA
  2. 2.Departments of Obstetrics and Gynecology, and Preventive MedicineUniversity of Southern California Keck School of MedicineLos AngelesUSA
  3. 3.Department of Laboratory MedicineHarvard Medical School and Children’s HospitalBostonUSA
  4. 4.Cancer Research Technology Program, Leidos Biomedical Research, Inc.Frederick National Laboratory for Cancer ResearchFrederickUSA

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