Brain structural changes in sync with the cycle

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Science Translational Medicine  22 Jul 2020:
Vol. 12, Issue 553, eabd3620
DOI: 10.1126/scitranslmed.abd3620


Neuroimaging and hormone assays over a full menstrual cycle reveal the effects of ovarian hormones on gray matter volumes in a patient.

Women have been understudied in biomedical research, potentially slowing progress toward efficacious treatments. For example, sex differences in drug pharmacokinetics may contribute to the two-fold greater rate of adverse reactions in women versus men. Such differences are particularly salient in mental health, where mood and anxiety disorders affect twice as many women as men, and sex hormones are an obvious potential contributor. However, few studies have addressed basic questions about the effects of cycling hormones on the brain, often with major methodological limitations such as inaccurate cycle-timing methods, and only one or two observation timepoints.

In a recent study, Taylor et al. hurdled these limitations, gathering daily magnetic resonance imaging (MRI) brain scans and blood hormone levels over 30 days in a single young woman. The goal was to investigate changes in the hippocampus and its cortical input pathways. Non-human models show that these regions are sensitive to ovarian hormones estradiol and progesterone. The post-ovulation rise in progesterone was tightly linked with an increase in gray matter volumes of the hippocampus and parahippocampal cortex, and a decrease in the entorhinal and perirhinal cortices. After taking an oral contraceptive to selectively suppress progesterone, the participant then showed no changes in gray matter volume. During memory formation, the parahippocampal versus perirhinal cortices receive information from different sensory processing pathways and convey it to the hippocampus, so progesterone may promote a bias toward memories for certain types of information. The findings have implications for aging as well as many psychiatric and neurological disease models, which show associations with hippocampal gray matter loss.

Several important questions remain. Only a single woman was examined, although there is clear evidence that menstrual cycle timing and hormonal fluctuations can vary widely, limiting generalizability. Additionally, the cellular changes that underlie changes in MRI gray matter volume cannot be resolved with MRI neuroimaging. Prior rodent research suggests that the development of new synaptic structures in neurons drives changes in MRI-based gray matter volume, but glial cells could also contribute. However, this is a precise and rigorous neuroimaging study of menstrual cycle effects on human brain structure, laying the groundwork for enduring insights about the effects of hormones on the brain.

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