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. 2019 Sep;79(5):314-319.
doi: 10.1080/00365513.2019.1622031. Epub 2019 Jun 4.

New reference intervals for cortisol, cortisol binding globulin and free cortisol index in women using ethinyl estradiol

Kristine Kollerøs Panton  1 , Gustav Mikkelsen  2   3 , Wenche Øiestad Irgens  2 , Ann Kristin Hovde  4 , Marte Wien Killingmo  4 , Monja Airin Øien  5 , Per Medbøe Thorsby  6 , Arne Åsberg  2
Affiliations

New reference intervals for cortisol, cortisol binding globulin and free cortisol index in women using ethinyl estradiol

Kristine Kollerøs Panton et al. Scand J Clin Lab Invest. 2019 Sep.

Abstract

Healthy women using contraceptives containing a low dose of an estrogen may have a higher serum concentration of cortisol (s-cortisol) and cortisol binding globulin (s-CBG) than the commonly used upper reference limits. There are no published reference intervals for s-cortisol, s-CBG, serum free cortisol index (s-FCI) or cortisol in saliva (sa-cortisol) for these women. The aim was to establish the above-mentioned reference intervals and document the differences in s-cortisol and s-CBG in one group of women using and another group not using ethinyl estradiol (EE). In this cross-sectional study, the reference limits presented were given as the 2.5 and 97.5 percentiles of the distribution of reference values in a population of 277 healthy volunteer women, aged 18-45 years. 157 women were not using any type of estrogen, while 120 women were using contraceptives containing a daily dose of 15-35 μg of EE. Serum and salivary cortisol, and serum CBG were measured using standard laboratory methods. S-FCI was calculated as s-cortisol/s-CBG. The reference intervals for s-cortisol in samples collected at 0800-1030 am in women using and not using EE contraception were: 284-994 nmol/L and 159-569 nmol/L respectively, and for s-CBG: 847-3366 nmol/L and 860-1940 nmol/L, respectively. For s-FCI and sa-cortisol, no clinically significant differences were found. Sa-cortisol may be the preferred measurand for evaluation of possible hypercortisolism in women using estrogens, since cortisol in saliva is not influenced by estrogen. If assessing morning s-cortisol and s-CBG in women using EE, we recommend using separate - and not the commonly used - reference intervals.

Keywords: Cortisol; agents; assay; chemiluminescence; corticosteroid binding globulin; estrogen contraceptive; ethinyl estradiol; reference values.

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