Methodological shortcomings of preclinical research on chemotherapy-induced cognitive impairment

Sex disparities are evident in the biological response to acute stressors, with a suggested influence of ovarian hormones on hypothalamic–pituitary–adrenal (HPA) axis functioning. This systematic review and meta-analysis investigates differences in HPA axis reactivity to acute psychosocial or physiological stressors between menstrual cycle phases. A systematic literature search of six databases resulted in 12 longitudinal studies (n = 182) examining HPA axis reactivity in healthy, naturally-cycling, non-breastfeeding participants aged between 18 and 45 years in at least two cycle phases. The quality of cortisol and menstrual cycle assessment was rated and a descriptive synthesis and meta-analysis of HPA axis reactivity between two broader and five more precise cycle phases was conducted. Three studies provided sufficient data for the meta-analysis and showed a significant, small-sized effect, indicating higher cortisol reactivity in the luteal than in the follicular cycle phase. More primary studies with high-quality menstrual cycle and cortisol assessment are needed. The review did not receive funding and was pre-registered (PROSPERO; CRD42020181632).