A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum

J Clin Endocrinol Metab. 2011 May;96(5):1533-40. doi: 10.1210/jc.2010-2395. Epub 2011 Mar 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Chromatography, High Pressure Liquid
  • Contraceptives, Oral, Hormonal / adverse effects
  • Cortisone / blood
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Hydrocortisone / urine*
  • Hypothalamo-Hypophyseal System / physiology
  • Immunoassay
  • Longitudinal Studies
  • Pituitary-Adrenal System / physiology
  • Postpartum Period / blood*
  • Postpartum Period / urine*
  • Pregnancy
  • Pregnancy Trimester, Third / blood
  • Prospective Studies
  • Tandem Mass Spectrometry
  • Transcortin / metabolism


  • Contraceptives, Oral, Hormonal
  • Transcortin
  • Cortisone
  • Hydrocortisone