Abstract
BACKGROUND: Fluctuations in oestrogen (E2) and progesterone (P4) shape brain morphology across menstrual cycles. Yet, it remains unclear how these hormonal dynamics translate into region-specific changes in grey matter structure. METHODS: Using structural magnetic resonance imaging (MRI), we assessed grey matter volume (GMV) and cortical thickness (CT) in 32 healthy women during the periovulatory phase (peak E2) and menstruation (low E2 and P4). Region-of-interest (ROI) and exploratory whole-brain analyses were performed, complemented by multiple regression models to assess associations between E2, P4, and brain morphology. Further, spatial colocalisation analyses were applied to link observed macrostructural changes with receptor density maps. FINDINGS: Predefined ROI analyses targeting the amygdala and the hippocampus yielded no significant effects after correction for multiple comparisons. While E2 correlated positively with parietal regions in the periovulatory phase, P4 exhibited robust phase-dependent associations with the cerebellar and fusiform volumes in the periovulatory phase, and with the frontal volumes and widespread CT during menstruation. Spatial colocalisation with hormone receptor distributions indicated stronger structural changes in regions with higher P4 receptor density. INTERPRETATION: These results identify P4 as a key modulator of brain morphology, with its effects varying according to the menstrual phase. Understanding the hormone-driven brain dynamics is essential for a more accurate model of female brain function and mental health. FUNDING: German Research Foundation.