Chemotherapy-induced estradiol reduction is associated with less relief of pre-chemotherapy anxiety in breast cancer patients

Chemotherapy-induced apoptosis of mature ovarian follicles in breast cancer patients likely results in decreased circulating estradiol (E 2 ), although this is rarely measured. Outside of cancer, sudden E 2 reductions (e.g., post-childbirth) are associated with increased anxiety and depressive symptoms. About half of breast cancer patients undergoing chemotherapy report anxiety and depressive symptoms, which is a major reason for discontinuing or changing chemotherapy treatment. This study examined the relationship between E 2 reductions and anxiety/depressive symptoms, during chemotherapy. As a secondary outcome, intolerance of uncertainty was also assessed. Blood samples and patient-reported questionnaires were collected from 77 breast cancer patients. Plasma E 2 concentrations were quantified using ELISA. Chemotherapy-induced reductions in circulating E 2 were associated with less relief from pre-chemotherapy anxiety symptoms and intolerance of uncertainty during chemotherapy, regardless of age and menopausal status. Conversely, participants whose E 2 concentrations did not decrease experienced relief from pre-chemotherapy anxiety symptoms and intolerance of uncertainty during chemotherapy. Similar trends were observed for depressive symptoms. These findings suggest that monitoring circulating E 2 levels may provide valuable mechanistical insights into patients’ psychological responses during chemotherapy and could inform more personalized approaches to supportive care. • Chemotherapy lowered circulating estradiol levels in most, but not all, patients. • Reductions in estradiol were associated with less relief from anxiety during chemotherapy. • No estradiol-mood cross-sectional or longitudinal associations were observed. • High pre-treatment estradiol may hinder anxiety relief over chemotherapy infusions.