Hormonal dynamics shape brain structural plasticity across the menstrual cycle: Insights from dense-sampling structural brain imaging of females with and without endometriosis

Abstract

Gonadal hormone fluctuations in females have been associated with symptoms of mental health, yet the underlying brain mechanisms remain understudied. Recent advances in neuroscience have shifted the paradigm towards longitudinal tracking, enabling the detection of subtle changes overlooked in conventional cross-sectional analyses. This dense-sampling approach acknowledges the rhythmic nature of gonadal hormone production. Our study employed three densely sampled females who underwent brain imaging and venipuncture (5 to 7 days per week) over the full menstrual cycle to investigate the impact of gonadal hormone variation on brain structure. In two healthy females with typical menstrual cycles, progesterone and progesterone/estradiol ratios were inversely associated with spatiotemporal structural brain patterns across the cycle. To probe the neural effects of hormonal dysregulation, we densely sampled a participant with endometriosis, an endocrine disorder affecting 10% of females in their reproductive years. Here, the spatiotemporal brain pattern was associated only with estradiol fluctuations. Our findings suggest that gonadal hormones are associated with short-term brain structural changes, with distinctions observed between typical and endometriosis cycles. This emphasizes the consideration of individual hormonal dynamics in understanding fluctuations in brain structural plasticity.