A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum
Abstract
CONTEXT: There is a paucity of longitudinal data on plasma and urinary cortisol levels during pregnancy using modern assays. Furthermore, conflicting data exist as to the effect of the low-dose oral contraceptive pill (OCP) on cortisol. DESIGN, SUBJECTS, AND MEASUREMENTS: We conducted a prospective longitudinal study on morning plasma cortisol (total and free), corticosteroid-binding globulin (CBG), and 24-h urinary free cortisol (UFC) levels in 20 pregnant women during the first, second, and third trimesters and 2-3 months postpartum compared with 12 subjects on low-dose OCP and 15 nonpregnant subjects not taking the OCP (control group). RESULTS: A progressive rise in total plasma cortisol, CBG, and 24-h UFC was demonstrated during pregnancy, peaking during the third trimester (mean 3-fold rise compared with controls). Plasma free cortisol increased 1.6-fold by the third trimester. In the OCP group, total plasma cortisol and CBG were 2.9- and 2.6-fold elevated, respectively, whereas 24-h UFC and plasma free cortisol were not significantly different from controls. Compared with liquid chromatography-mass spectrometry, a commercial immunoassay underestimated mean total plasma cortisol concentrations by 30% during second and third trimesters and in OCP users and overestimated UFC levels by 30-35% during pregnancy. CONCLUSIONS: Our study demonstrated elevations in total plasma cortisol and CBG concentrations during pregnancy and with low-dose OCP use. Pregnancy was also associated with significant increases in plasma free cortisol and UFC, suggesting that the rise in total plasma cortisol is contributed to by up-regulation of the maternal hypothalamic-pituitary-adrenal axis in addition to elevated CBG.
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From week 22 of gestation onward, free cortisol levels increase significantly, with a further rise immediately preterm due to a fall in CBG; cortisol levels return to normal after delivery.
“From week 22 of gestation onward, free cortisol levels also increase significantly, with a further rise immediately preterm due to a fall in CBG (42, 119); cortisol levels return to normal after delivery (40).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [42]
The Plasma free cortisol section (page unavailable) reports an increase during pregnancy, but its post hoc comparison reached significance only in the third trimester, not specifically from week 22. The Discussion (page unavailable) describes a further rise in the final weeks alongside falling CBG, while noting that this study did not assess that period. The postpartum clause has a separate citation in the citing sentence and is not attributed to this source here. (LLM, conf=0.85)
Experimental — accuracy not yet measuredInterpretation of diagnostic results in pregnancy requires thorough consideration of pregnancy-associated physiological changes of adrenocortical function.
“Interpretation of the diagnostic results requires thorough consideration of pregnancy-associated physiological changes of adrenocortical function (42).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [42]
During normal pregnancy, circulating cortisol concentrations are increased 2- to 3-fold, with a continuous increase from the first trimester onward due to increases in CBG levels.
“During normal pregnancy, circulating cortisol concentrations are increased 2-to 3-fold, with a continuous increase from the first trimester onward due to increases in CBG levels (40,42).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [42]
Women with increased estrogen levels due to oral or transdermal contraceptives or pregnancy have increased total serum cortisol due to an increase in CBG.
“women who have increased estrogenlevels due to oral or transdermal contraceptives or pregnancy, have increased total serum cortisol due to an increase in CBG”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [248]
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References 39 · Cited by 394
- Authors
- Jung, C., Ho, J. T., Torpy, D. J., Rogers, A., Doogue, M., Lewis, J. G., Czajko, R. J., & Inder, W. J.
- Affiliations
- The University of Melbourne (AU)
- Royal Adelaide Hospital (AU)
- Flinders University (AU)
- Canterbury Health Laboratories (NZ)
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Jung, Caroline
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-05
- Volume
- 96
- Issue
- 5
- Pages
- 1533-1540
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2154189263
- Cited by
- 394
- References
- 39
- Citations by year
- 2026: 30 · 2025: 31 · 2024: 34 · 2023: 26 · 2022: 30 · 2021: 33 · 2020: 31 · 2019: 36 · 2018: 25 · 2017: 24 · 2016: 26 · 2015: 24 · 2014: 18 · 2013: 14 · 2012: 9
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- University of Melbourne
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy-related medical research
- Keywords
- plasma cortisol, urinary free cortisol, pregnancy, postpartum period, corticosteroid-binding globulin, hypothalamic-pituitary-adrenal axis, liquid chromatography-mass spectrometry
- MeSH terms
- Adult, Chromatography, High Pressure Liquid, Contraceptives, Oral, Hormonal, Cortisone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Immunoassay, Longitudinal Studies, Pituitary-Adrenal System, Pregnancy, Pregnancy Trimester, Third, Prospective Studies, Transcortin, Body Mass Index, Postpartum Period, Tandem Mass Spectrometry
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