Nocturnal Cortisol Levels May Provide a Noninvasive Biomarker of Ovarian Cancer Severity


Key Points

  • Women with late-stage ovarian cancer had higher nocturnal cortisol levels.
  • Elevated nocturnal cortisol levels prior to surgery were associated with shorter survival time.
  • Nocturnal cortisol levels may provide a noninvasive biomarker of ovarian cancer severity.

Elevated nocturnal cortisol levels prior to surgery in patients with ovarian cancer were associated with shorter survival time, according to a study by Schrepf et al in Psychoneuroendocrinology. Thus, night-time cortisol levels may prove to be a noninvasive biomarker of ovarian cancer disease severity.

Despite numerous advances in the understanding of the epidemiology and treatment of ovarian cancer, survival rates remain low. Recent research has demonstrated the role of neuroendocrine signaling on a variety of pathways associated with ovarian tumor growth, including angiogenesis, invasion, anoikis, and promotion of inflammation in the tumor microenvironment. Hypothalamic-pituitary-adrenal deregulation has also been observed in patients with certain cancers, but its possible role in ovarian cancer has not been widely researched.

Thus, Schrepf and colleagues conducted a prospective study examining the association among hypothalamic-pituitary-adrenal activity, tumor-associated inflammation, and survival in patients with ovarian cancer prior to treatment. In particular, the researchers wanted to examine the role of abnormal diurnal cortisol rhythms. Flattened diurnal cortisol rhythms have been linked to decreased survival in patients with breast, lung, and renal cell carcinomas.

Study Details

Included in the study were 113 women with no history of cancer. Eligible women had primary invasive epithelial ovarian, primary peritoneal, or fallopian tube carcinoma and were classified according to disease stage (I–II being early stage and III–IV being late stage). Most patients went on to receive at least six cycles of platinum and taxane combination chemotherapy.

Salivary cortisol was collected by participants three times daily for 3 days immediately prior to surgery. Participants were instructed to collect the first sample upon waking, the second sample at 5:00 PM, and the final sample at bedtime.

Association Between Late-Stage Cancer and Elevated Nocturnal Cortisol Levels

Late-stage disease was associated with higher nocturnal cortisol levels (P = .005) and marginally associated with flattened slope (P = .07). In addition, poorer physical well-being was associated with elevated nocturnal cortisol levels (P = .022) and flattened cortisol slope (P = .042).

Elevated nocturnal cortisol levels prior to surgery were independently associated with shorter survival time after controlling for disease stage, tumor grade, cytoreduction, and age (hazard ratio = 1.455, 95% confidence interval [CI] = 1.059–1.998, P = .021). A patient whose nocturnal cortisol level was 2.22 nmol/L (one standard deviation above the mean) would have a 46% greater risk of death compared with a patient whose nocturnal cortisol level was 1.44 nmol/L. Patients with low nocturnal cortisol levels had a median overall survival of 7.3 years compared with 3.3 years in those with high night cortisol levels.

Closing Thoughts

The key finding of this study is that dysregulated function of the hypothalamic-pituitary-adrenal axis, evidenced by flattened diurnal cortisol slope and elevated nocturnal cortisol levels, is associated with decreased survival time in patients with ovarian cancer. The researchers also noted that the relationship between cortisol dysregulation and overall survival does not appear to be mediated by sleep dysregulation, symptoms of disease, or depression.

The investigators concluded, “Night-time cortisol levels may provide a noninvasive biomarker of ovarian cancer disease severity that is independent of established pathological markers.”

Andrew Schrepf, of the Department of Psychology, University of Iowa, Iowa City, Iowa, is the corresponding author of this article in Psychoneuroendocrinology.

This research was funded in part by grants from the National Cancer Institute. The authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.