Longitudinal 7T MRI reveals volumetric changes in subregions of human medial temporal lobe to sex hormone fluctuations

The hippocampus and surrounding medial temporal lobe (MTL) are critical for memory processes, with local atrophy linked to memory deficits. Animal work shows that MTL subregions densely express sex hormone receptors and exhibit rapid structural changes synchronized with hormone fluctuations. Such transient effects in humans have thus far not been shown. By combining a dense-sampling protocol, ultra-high field neuroimaging and individually-derived segmentation analysis, we demonstrate how estradiol and progesterone fluctuations affect MTL subregion volumes across the human menstrual cycle. Twenty-seven healthy women (19-34 years) underwent 7T MRI at six timepoints to acquire T1-weighted and T2-weighted images. Linear mixed-effects modeling showed positive associations between estradiol and parahippocampal cortex volume, progesterone and subiculum and perirhinal Area 35 volumes, and an estradiol*progesterone interaction with CA1 volume. We confirmed volumetric changes were not driven by hormone-related water (cerebral spinal fluid) or blood-flow (pulsed arterial spin labeling) changes. These findings suggest that sex hormones alter structural brain plasticity in subregions that are differentially sensitive to hormones. Mapping how endogenous endocrine factors shape adult brain structure has critical implications for womens health during the reproductive years as well as later in life, such as increased dementia risk following perimenopause, a period of pronounced sex hormone fluctuations.