Hypothalamic–Pituitary–Adrenal Axis Dysfunction in People With Cancer: A Systematic Review

ABSTRACT Purpose Cancer can be a source of significant psychological and physical stress. Prolonged stressful stimuli can influence the stress response, mediated by the hypothalamic–pituitary–adrenal (HPA) axis. However, there is limited literature investigating HPA axis function in patients with cancer. Methods A systematic literature review of case–control studies was conducted comparing individuals with and without cancer examining the HPA axis function. Databases (MEDLINE, PubMed, Scopus) were searched from inception to May 2023. Results Seventeen studies met eligibility criteria: nine unstimulated‐cortisol studies and eight reporting the effect of HPA stimulation or suppression. Sixteen studies reported altered levels of HPA function in cancer patients relative to controls, including 13 reporting increased baseline or hyperactive cortisol responses, and four—decreased baseline cortisol or blunted cortisol responses, two of which had patient groups with now known cortisol‐suppressing treatments. HPA dysfunction was observed in patients of both sexes, diverse ages, stages of cancer and cancer treatments. Six papers reported on clinical outcomes with cases experiencing higher levels of fatigue, stress, poor memory, poor well‐being and disturbed sleep. There was significant heterogeneity in methodologies across the studies. Conclusion HPA dysfunction was common in patients with cancer relative to cancer‐free controls. The majority of studies in cancer reported an increased baseline cortisol and increased response to HPA stimulation. There is a need for well‐powered studies using standardised methodology examining the mechanisms of HPA dysregulation and their health outcomes, to enable the development of appropriate tools for the diagnosis and management of HPA dysfunction in cancer. This systematic review of 17 studies comparing HPA axis function in individuals with cancer as compared to controls suggests that HPA dysregulation is common in people with cancer. There was significant variability in methodologies used to measure HPA dysregulation, which limits the interpretation of findings, and few only studies examined the impact of HPA dysregulation on patient outcomes. There is a need for studies that use a standardised approach to HPA axis measurement and examine patient outcomes to determine its clinical impact.