Hippocampal volume and affect in response to fluctuating estrogens in menstrual cycle irregularity: A longitudinal single-subject study

Abstract

AbstractBackground The menstrual cycle is a critical indicator of women's reproductive, physical, and mental health, influenced by neuromodulatory sex steroid hormones, including estrogens like 17β-estradiol, and estrone. Irregular menstrual cycles can lead to various health conditions. Understanding the relationship between endogenous hormone fluctuations and brain function across the menstrual cycle is essential for comprehending mental health disorders prevalent in women. Here, we investigated the impact of hormonal variations on hippocampal morphology and affect in a participant with an irregular menstrual cycle. Methods In this dense-sampling longitudinal study, a healthy female with an irregular menstrual cycle underwent testing for five consecutive weeks, covering mostly the follicular phase and ovulation. Daily blood draws provided measurements of estradiol, estrone, and progesterone. T1-weighted MRI scans assessed bilateral hippocampal volumes. Psychological measures of positive and negative affect were collected each session. Statistical analyses included cubic regression curves, Spearman correlations, and mediation regression models to explore hormonal associations with hippocampal morphology and affect. Results Fluctuations were observed in hormonal concentrations, hippocampal volume, and affect across the 25 testing days. Estradiol and estrone correlated significantly with hippocampal volume, while progesterone did not show any significant association. Increased estrogen levels were linked to decreased positive affect, mediated by hippocampal volume fluctuations. Increased estrogen levels were further associated with increased negative affect, however, independently of hippocampal changes. Conclusion This study sheds light on the complex relationship between endogenous hormone fluctuations, hippocampal morphology, and affect in a participant with an irregular menstrual cycle. The findings suggest potential roles of estrogens and estrone in affect regulation, with implications for women's mental health and brain function. Further research is warranted to explore these associations in larger samples and various menstrual cycle patterns.