Comparability of serum, plasma, and urinary estrogen and estrogen metabolite measurements by sex and menopausal status
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.
KeywordsEstrogens Estrogen metabolites Urine Serum Plasma Comparison
This work was supported by the Intramural Research Program of the National Cancer Institute.
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Conflict of interest
All authors declare that they have no conflicts of interest.
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