Reproducibility of plasma and urine biomarkers among premenopausal and postmenopausal women from the Nurses' Health Studies

Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):938-46. doi: 10.1158/1055-9965.EPI-09-1318. Epub 2010 Mar 23.


Background: Temporal variability of biomarkers should be evaluated before their use in epidemiologic studies.

Methods: We evaluated the reproducibility, using intraclass correlation coefficients (ICC), of 77 plasma and 9 urinary biomarkers over 1 to 3 years among premenopausal (n = 40) and postmenopausal (n = 35-70) participants from the Nurses' Health Study and Nurses' Health Study II.

Results: Plasma and urinary stress hormones and melatonin were measured among premenopausal women, whereas melatonin and the remaining biomarkers were measured in postmenopausal women. ICCs were good to excellent for plasma carotenoids (0.73-0.88), vitamin D analytes (0.56-0.72), bioactive somatolactogens (0.62), soluble leptin receptor (0.82), resistin (0.74), and postmenopausal melatonin (0.63). Reproducibility was lower for some of the plasma fatty acids (0.38-0.72), matrix metalloproteinases (0.07-0.91), and premenopausal melatonin (0.44). The ICCs for plasma and urinary phytoestrogens were poor (< or = 0.09) except for enterolactone (plasma, 0.44; urinary, 0.52). ICCs for the stress hormones among premenopausal women ranged from 0 (plasma cortisol) to 0.45 (urinary dopamine).

Conclusions: Our results indicate that for the majority of these markers, a single measurement can reliably estimate average levels over a 1- to 3-year period in epidemiologic studies. For analytes with fair to good ICCs, reproducibility data can be used for measurement error correction. Analytes with poor ICCs should only be used in settings with multiple samples per subject or in populations in which ICCs are higher.

Impact: This article summarizes the feasibility of the use of >80 biomarkers in epidemiologic studies in which only one biospecimen is available to represent longer term exposure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Biomarkers / urine*
  • Chromatography, Liquid
  • Female
  • Humans
  • Middle Aged
  • Nurses
  • Postmenopause
  • Premenopause
  • Reproducibility of Results
  • Tandem Mass Spectrometry


  • Biomarkers