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

doi:10.1016/j.psyneuen.2015.01.010

Diurnal cortisol and survival in epithelial ovarian cancer

Psychoneuroendocrinology. 2015 Mar:53:256-67. doi: 10.1016/j.psyneuen.2015.01.010. Epub 2015 Jan 20.

Authors

Affiliations

¹ Department of Psychology, University of Iowa, E11 Seashore Hall, Iowa City, IA 52242, USA. Electronic address: Andrew-schrepf@uiowa.edu.
² Division of Gynecologic Oncology, Washington University School of Medicine, Maternity Building-660 South Euclid, Campus Box 8064, St. Louis, MO 63110, USA. Electronic address: thakerp@wudosis.wustl.edu.
³ Department of Obstetrics and Gynecology, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA; Department of Anatomy and Cell Biology, University of Iowa, USA. Electronic address: michael-goodheart@uiowa.edu.
⁴ Department of Obstetrics and Gynecology, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA. Electronic address: david-bender@uiowa.edu.
⁵ Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, 300 Medical Plaza Driveway, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA. Electronic address: GSlavich@mednet.ucla.edu.
⁶ Department of Urology, University of Iowa, 3 Roy Carver Pavilion, 200 Hawkins Dr, Iowa City, IA 52242, USA; Department of Pathology, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA. Electronic address: laila-dahmoush@uiowa.edu.
⁷ Department of Medical Social Sciences, Northwestern University, 633 N. Saint Clair St., 19th Floor, Chicago, IL 60611, USA; Department of Psychiatry and Behavioral Sciences, Northwestern University, 446 East Ontario, #7-200, Chicago, IL 60611, USA. Electronic address: fpenedo@northwestern.edu.
⁸ Division of Gynecologic Oncology, Oregon Health & Science University, Center for Women's Health, Kohler Pavilion, 7th Floor, 808 S.W. Campus Drive, Portland, OR 97239, USA.
⁹ Department of Obstetrics and Gynecology, Florida International University School of Medicine, 5000 University Dr, Coral Gables, FL 33146, USA. Electronic address: lemendez@comcast.net.
¹⁰ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA; Department of Microbiology, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA; Holden Comprehensive Cancer Center, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA. Electronic address: David-lubaroff@uiowa.edu.
¹¹ Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, 300 Medical Plaza Driveway, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA; Department of Medicine, UCLA School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA. Electronic address: coles@ucla.edu.
¹² Department of Gynecologic Oncology, UT MD Anderson Comprehensive Cancer Center, 1155 Herman Pressler, Unit Number: 1362, Houston, TX 77030, USA; Department of Cancer Biology, UT MD Anderson Comprehensive Cancer Center, 1155 Herman Pressler, Unit Number: 1362, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.
¹³ Department of Psychology, University of Iowa, E11 Seashore Hall, Iowa City, IA 52242, USA; Department of Obstetrics and Gynecology, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA; Department of Urology, University of Iowa, 3 Roy Carver Pavilion, 200 Hawkins Dr, Iowa City, IA 52242, USA; Holden Comprehensive Cancer Center, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA. Electronic address: susan-lutgendorf@uiowa.edu.

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.

Keywords: Biological markers; Chronobiology disorders; Hydrocortisone; Inflammation; Ovarian neoplasms.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Ascitic Fluid / immunology
Carcinoma, Ovarian Epithelial
Circadian Rhythm*
Female
Humans
Hydrocortisone / immunology
Hydrocortisone / metabolism*
Hypothalamo-Hypophyseal System / metabolism*
Inflammation / immunology
Inflammation / metabolism
Interleukin-6 / immunology
Middle Aged
Neoplasms, Glandular and Epithelial / metabolism*
Neoplasms, Glandular and Epithelial / mortality
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / mortality
Pituitary-Adrenal System / metabolism*
Prognosis
Proportional Hazards Models
Saliva / chemistry

Substances

IL6 protein, human
Interleukin-6
Hydrocortisone

Abstract

Publication types

MeSH terms

Substances

Grants and funding