Absolute and relative concentrations of
estrogens and
estrogen metabolites are important for clinical decisions as well as for epidemiologic, experimental, and clinical research on hormonal
carcinogenesis. RIA and ELISA are routinely used for measuring
estrogen metabolites in blood and urine due to efficiency and low cost. Here, we compare absolute and ranked concentrations of
estrone,
estradiol, and
estriol measured by indirect RIA and of
2-hydroxyestrone and 16alpha-hydroxyestrone measured by ELISA to the concentrations obtained using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures 15
estrogen metabolites concurrently. We used overnight urine samples collected from control women (362 premenopausal and 168 postmenopausal) participating in a population-based case-control study of
breast cancer among Asian American women ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute concentrations for the five
estrogen metabolites ranged from 1.6 to 2.9 and 1.4 to 11.8 times higher in premenopausal and postmenopausal women, respectively (all P < 0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r (r(s)) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and moderately correlated (r(s) = 0.4-0.8) in postmenopausal women. Measurements of the 2-hydroxyestrone:16alpha-hydroxyestrone ratio, a putative
biomarker of
breast cancer risk, were moderately correlated in premenopausal women (r(s) = 0.6-0.7) but only weakly correlated in postmenopausal women (r(s) = 0.2). LC-MS/MS had higher intraclass correlation coefficients (> or =99.6%) and lower coefficients of variation (< or =9.4%) than ELISA (> or =97.2% and < or =14.2%) and RIA (> or =95.2% and < or =17.8%). Comparison with the LC-MS/MS method suggests that the widely used RIA and ELISA
estrogen metabolite measures may be problematic, especially at low
estrogen metabolite levels characteristic of postmenopausal women.