New reference intervals for cortisol, cortisol binding globulin and free cortisol index in women using ethinyl estradiol
Open accessAbstract
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.
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Higher cutoffs for morning plasma cortisol have been suggested for women using COCs.
“Higher cutoffs for morning plasma cortisol have been suggested for women using COCs (19).”
From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [19]
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- Authors
- Panton, K. K., Mikkelsen, G., Irgens, W. Ø., Hovde, A. K., Killingmo, M. W., Øien, M. A., Thorsby, P. M., & Åsberg, A.
- Affiliations
- Fürst Medical Laboratory, Oslo, Norway;
- Norwegian University of Science and Technology (NO)
- St Olav's University Hospital (NO)
- Oslo University Hospital (NO)
- Corresponding author
- Panton, Kristine Kollerøs
- Venue
- Scandinavian Journal of Clinical and Laboratory Investigation
- Publisher
- Informa UK Limited
- Published
- 2019-06-04
- Volume
- 79
- Issue
- 5
- Pages
- 314-319
- ISSN
- 0036-5513 (ISSN-L)
- 1502-7686
- OpenAlex
- W2948044763
- Cited by
- 25
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 2 · 2020: 1
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Scandinavian Journal of Clinical and Laboratory Investigation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Zenodo (CERN European Organization for Nuclear Research) (cc-by)
- Funders
- St. Olavs Hospital Universitetssykehuset i Trondheim
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- reference values, serum cortisol, corticosteroid-binding globulin, salivary cortisol, ethinyl estradiol, oral contraceptives, estrogen, women, hypercortisolism, morning cortisol
- MeSH terms
- Adolescent, Adult, Carrier Proteins, Ethinyl Estradiol, Female, Humans, Hydrocortisone, Middle Aged, Reference Values, Young Adult
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