Diurnal cortisol and survival in epithelial ovarian cancer

Andrew Schrepf, Premal H. Thaker, Michael J. Goodheart, David Bender, George M. Slavich, Laila Dahmoush, Frank Penedo, Koen DeGeest, Luis Mendez, David M. Lubaroff, Steven W. Cole, Anil K. Sood, Susan K. Lutgendorf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Introduction: Hypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment. Materials and methods: Participants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables. Results: Each cortisol measure was associated with decreased survival time, adjusting for covariates (all p< .041). A one standard deviation increase in night cortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r> 36, all p< .017). Discussion: Abnormal cortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity.

Original languageEnglish (US)
Pages (from-to)256-267
Number of pages12
JournalPsychoneuroendocrinology
Volume53
DOIs
StatePublished - Mar 1 2015

Keywords

  • Biological markers
  • Chronobiology disorders
  • Hydrocortisone
  • Inflammation
  • Ovarian neoplasms

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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