Brain anatomy in major hormonal transition phases: Longitudinal and cross-sectional volume associations with menarche and menopause

Background Hormonal transition phases represent windows of increased neuroplasticity across the female lifespan. In this study, we aim to investigate the brain anatomical architecture of hormonal transition phases by directly comparing menarche, as a period of rising levels of steroid hormones, and menopause, as a time of declining levels. Methods We fit linear models on cross-sectional and linear mixed-effect models on longitudinal magnetic resonance imaging (MRI) datasets, to explore the effects of menarche onset (ABCD study data, N cross-sectional =1274, N longitudinal =611) and transition into menopause (UK Biobank data, N cross-sectional =1614, N longitudinal =212) on 66 cortical and 135 subcortical brain volumes, and to identify brain structures with opposing but regional overlapping effects in both periods. Models were adjusted for age and corrected for multiple comparison (P <.05; FDR-corrected). Results Cross-sectionally, using a between-subject design, 83 brain volumes showed effects of menarche-onset and 17 volumes showed effects of menopause-transition. Of these, seven brain volumes were significantly affected by both transitional periods, showing opposing directional volume changes. Longitudinally, using a within-subject design, 56 brain volumes exhibited menarche effects, of which 46 replicated cross-sectionally. No menopause effect survived correction for multiple comparison, likely due to limited longitudinal sample size. Conclusion Our findings confirm regionally overlapping brain structural alteration between the two hormonal phases – menarche and menopause – showing the hypothesized opposite effect directions. Additionally, our results show the robustness of menarche effects, which converged across cross-sectional and longitudinal study designs. Taken together, our results contribute to a better understanding of hormone related neuroplasticity, emphasizing the importance of not only understanding individual phases, but understanding the overarching patterns across the female reproductive lifespan.