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Clin Chem. 2000 Apr;46(4):551-9.

Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women.

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Referencelaboratory, National Institute of Occupational Health, Lerso Parkallé 105, DK-2100 Copenhagen, Denmark. Copenhagen N, Denmark.

Erratum in

  • Clin Chem 2001 Oct;47(10):1877.



Concentrations of physiological response variables fluctuate over time. The present study describes within-day and seasonal fluctuations for total cholesterol, dehydroepiandrosterone sulfate (DHEA-S), hemoglobin A(1c) (HbA(1c)), IgA, prolactin, and free testosterone in blood, and estimates within- (CV(i)) and between-subject (CV(g)) CVs for healthy women. In addition, the index of individuality, prediction intervals, and power calculations were derived.


A total of 21 healthy female subjects participated in the study. Using a random effects analysis of variance, we estimated CV(g) and total within-subject variation (CV(ti)), i.e., the combined within-subject and analytical variation, from logarithmically transformed data. Analytical variation was subtracted from CV(ti) to give CV(i). CV(i) was estimated from samples taken monthly during 1 year (CV(iy)), weekly during 1 month (CV(im)), and six times within 1 day (CV(id)).


A cyclic seasonal variation was demonstrated for total cholesterol, DHEA-S, HbA(1c), prolactin, and free testosterone. Within-day variation was shown for prolactin and free testosterone. The overall mean values for the group and the variability (CV(iy) and CV(g)) were: 5.1 mmol/L, 13% [corrected], and 12% [corrected] for total cholesterol; 6.6 micromol/L, 20% [corrected], and 49% [corrected] for DHEA-S; 30% [corrected], 7.0% [corrected], and 7.5% [corrected] for HbA(1c)/hemoglobin(total); 2.1 g/L, 5.9%, and 13% for IgA; 136 mIU/L, 58% [corrected], and 63% [corrected] for prolactin; and 5.4 pmol/L, 55% [corrected], and 68% [corrected] for free testosterone.


Collecting samples at specific hours of the day or times of the year may reduce high biological variation. Alternatively, the number of individuals may be increased and a paired study design chosen to obtain adequate statistical power.

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