Structural Brain Changes Across the Female Lifespan: Puberty, Pregnancy, and Menopause Show Shared and Distinct Trajectories

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Abstract

The female brain undergoes substantial reorganization during major hormonal transitions, yet whether puberty, pregnancy, and menopause engage shared or distinct neuroplastic mechanisms remains unknown. We conducted the first study comparing longitudinal structural brain changes across all three transitions using identical analytical methods (n=1292), with stable control groups to isolate transition-specific effects. Both pubertal girls transitioning through menarche and women transitioning to motherhood showed cortical gray matter reductions across the majority of examined regions, with cross-cohort comparisons confirming broad mostly convergence but also regional divergence across the cortex. The menopausal transition showed a fundamental divergence from both puberty and pregnancy, as women transitioning through menopause showed no accelerated volumetric loss, while stable pre- and postmenopausal control groups did. These findings demonstrate that puberty and pregnancy share a broadly convergent signature of cortical remodeling, while menopause represents a qualitatively distinct neuroplastic state defined by the absence rather than acceleration of volumetric change.

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