Progesterone shapes medial temporal lobe volume across the human menstrual cycle

The rhythmic production of sex steroid hormones is a central feature of the mammalian endocrine system. In rodents and nonhuman primates, sex hormones are powerful regulators of hippocampal subfield morphology. However, it remains unknown whether intrinsic fluctuations in sex hormones alter hippocampal morphology in the human brain. In a series of dense-sampling studies, we used high-resolution imaging of the medial temporal lobe (MTL) to determine whether endogenous fluctuations (Study 1) and exogenous manipulation (Study 2) of sex hormones alter MTL volume over time. Across the menstrual cycle, intrinsic fluctuations in progesterone were associated with volumetric changes in CA2/3, entorhinal, perirhinal, and parahippocampal cortex. Chronic progesterone suppression abolished these cycle-dependent effects and led to pronounced volumetric changes in entorhinal cortex and CA2/3 relative to freely cycling conditions. No associations with estradiol were observed. These results establish progesterone’s ability to rapidly and dynamically shape MTL morphology across the human menstrual cycle. Highlights Sex hormones are powerful regulators of hippocampal plasticity in mammals. The impact of hormone fluctuations on hippocampal morphology in humans is unknown. High resolution imaging of the MTL was conducted across two 30-day periods. Progesterone dynamically shapes MTL volume across the human menstrual cycle. Chronic progesterone suppression abolishes cycle-dependent changes.