Estradiol, Emotion Regulation, and the Limbic System: Effects on Gray Matter Volume.

Background: Mastering emotion regulation is crucial for social skills and mental health. Hormonal fluctuations, particularly in estradiol (E2) levels across the menstrual cycle, significantly impact emotion processing. E2 is known to influence emotion regulation, mental health, and the plasticity of limbic and striatal regions, which are involved in emotion processing and are rich in E2 receptors. Although research indicates that E2 levels may impact gray matter volume (GMV) of limbic and striatal areas, sufficient causal evidence is missing so far. Furthermore, because of the additional fluctuations of progesterone across the menstrual cycle, the sole impact of E2 on brain volume has been difficult to disentangle. Methods: To isolate the effects of E2 from other fluctuating sex hormones, we used a randomized, placebo-controlled, double-blind, crossover design and administered oral E2 to 27 naturally cycling females during their early follicular phase (low endogenous sex hormone levels). We analyzed emotion regulation strategies and E2 levels to assess their impact on regional GMV. Results: Our data showed that a rapid increase of E2 was negatively associated with right striatal GMV. Moreover, greater use of reappraisal was associated with reduced GMV of the right striatum. Rapidly increased E2 did not influence GMV of other limbic regions. Conclusions: These results highlight that rapid increases in E2 and individual differences in emotion regulation dynamically modulate GMV. This offers important implications for female mental and brain health associated with hormonal fluctuations. Considering female endocrine profiles improves hormone-informed health care and therefore supports individualized medicine.