Implications of Cortisol in Cognitive Impairment Observed in Cancer Patients: A Systematic Review

INTRODUCTION: Cancer-related cognitive impairment (CRCI) is a frequent adverse effect observed in patients, but the underlying mechanisms are still unclear. Cortisol has been proposed as a potential contributor to CRCI, so the aim of this review is to systematically evaluate the evidence on the role of cortisol in CRCI. METHODS: This review followed PRISMA guidelines and was registered in PROSPERO (CRD42024570561). The search was conducted in PubMed, Web of Science, SCOPUS, ProQuest, OSF PREPRINTS, OATD, NDLTD Global E-Theses and Dissertations, and EBSCO. Inclusion criteria were studies on adult cancer patients/survivors assessing cortisol and CRCI, published in English from inception to January 30, 2025. The risk of bias was analyzed with the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and a qualitative GRADE-like summary of the certainty of the evidence. RESULTS: Twelve articles were finally included and analyzed using content analysis methods. Overall, findings suggest that altered diurnal cortisol rhythm (i.e. blunted cortisol secretion pattern) might be involved in CRCI; although results are inconsistent and the exact mechanisms remain unknown. Stress response associated to diagnosis, surgery, and life changes, as well as certain treatments, of cancer patients may contribute to dysregulated cortisol secretion, which in turn has been linked to CRCI. Additionally, personality traits and sociodemographic factors may act as mediators between cortisol release and CRCI. CONCLUSION: Recent data suggest cortisol relates to CRCI; however, future research should standardize cognitive outcomes and cortisol assessment methods, and consider clinical, sociodemographic, and psychological factors that may modulate stress responses.