Functional brain network topology across the menstrual cycle is estradiol dependent and correlates with individual well-being.

The menstrual cycle (MC) is a sex hormone-related phenomenon that repeats itself cyclically during the woman's reproductive life. In this explorative study, we hypothesized that coordinated variations of multiple sex hormones may affect the large-scale organization of the brain functional network and that, in turn, such changes might have psychological correlates, even in the absence of overt clinical signs of anxiety and/or depression. To test our hypothesis, we investigated longitudinally, across the MC, the relationship between the sex hormones and both brain network and psychological changes. We enrolled 24 naturally cycling women and, at the early-follicular, peri-ovulatory, and mid-luteal phases of the MC, we performed: (a) sex hormone dosage, (b) magnetoencephalography recording to study the brain network topology, and (c) psychological questionnaires to quantify anxiety, depression, self-esteem, and well-being. We showed that during the peri-ovulatory phase, in the alpha band, the leaf fraction and the tree hierarchy of the brain network were reduced, while the betweenness centrality (BC) of the right posterior cingulate gyrus (rPCG) was increased. Furthermore, the increase in BC was predicted by estradiol levels. Moreover, during the luteal phase, the variation of estradiol correlated positively with the variations of both the topological change and environmental mastery dimension of the well-being test, which, in turn, was related to the increase in the BC of rPCG. Our results highlight the effects of sex hormones on the large-scale brain network organization as well as on their possible relationship with the psychological state across the MC. Moreover, the fact that physiological changes in the brain topology occur throughout the MC has widespread implications for neuroimaging studies.