Role of cortisol ultradian pulsatility in human pregnancy: a case-control study

Background Cortisol concentrations follow an ultradian rhythm, and these hormone pulses are an important factor governing gene transcription in target tissue. The maternal hypothalamic–pituitary–adrenal axis undergoes dramatic activation during pregnancy with resultant increased circulating cortisol. However, little is known about changes that might occur in pulsatility during this period. We tested our hypothesis that pulse frequency and amplitude are altered during pregnancy. Methods Study visits were at the Edinburgh Royal Infirmary. We recruited eligible women aged 16–45 years with body-mass index of less than 25 kg/m 2 . Exclusion criteria were diabetes, smoking, and use of glucocorticoid therapy or hormonal contraception. Cortisol was measured by ELISA in serum obtained every 10 min for 6 h from five healthy pregnant women (16–24 weeks' gestation [P1] and 30–36 weeks' [P2]), and from three non-pregnant controls [NP]) during the luteal phase of the menstrual cycle. Women gave written, informed consent, and ethics approval was given by the local research ethics committee. Data are given as mean (SD). Findings Fasting serum cortisol, pulse frequency, and pulse amplitude were all significantly higher in pregnancy than in non-pregnancy (all p Interpretation We show that in normal human pregnancy, increased frequency and amplitude of cortisol pulsatility might be a novel mechanism underlying pregnancy complications related to cortisol exposure such as intrauterine growth restriction. Future studies will investigate whether the pulsatility of bioavailable cortisol in peripheral tissue is altered, and characterise the ultradian rhythm of cortisol in high-risk pregnancy groups. Funding Tommy's.