Phase-Specific Variations in Brain Network Connectivity with Ovarian Hormones

Females are twice as likely as males to experience affective disorders, a disparity emerging at puberty and declining at menopause, suggesting a role for ovarian hormones. One hypothesis is that when estradiol and progesterone are high—women experience a “window of vulnerability” to mood disorders[1]. Emerging studies also suggest that functional brain connectivity fluctuates with hormonal levels[2]. We investigated how ovarian hormones influence brain network organization across the menstrual cycle in 16 healthy menstruating women (ages20–35). fMRI data were collected in 3 menstrual phases to construct functional connectivity. We applied the Louvain algorithm to detect communities in each phase, yielding phase-specific partitions. Nodes frequently changing modular assignment were tracked and analyzed using a linear mixed-effects model. We found significant network reorganization across the cycle, especially in frontoparietal nodes shifting to the default mode network, a key region in depression[3]. Importantly, the relationship between hormone levels and modular consistency—which measures the likelihood that a pair of nodes belongs to the same module across subjects varied by phase, suggesting that menstrual phase modulates hormone-brain interactions. Also, we speculate that this finding may be due to changing levels of hormone receptors in the brain throughout the menstrual cycle. These results highlight the dynamic influence of ovarian hormones on brain networks and emphasize the importance of considering menstrual phase in women’s mental health research.