Fluctuations in sex hormones across the menstrual cycle may influence brain structure, with progesterone showing stronger and more consistent associations than estradiol, according to a study published in eBioMedicine.
In a structural magnetic resonance imaging (MRI) study of 32 healthy women, researchers compared brain morphology during menstruation, when hormone levels are low, with the periovulatory phase, when estradiol peaks and progesterone begins to rise. Total gray matter volume was modestly but statistically significantly higher during the periovulatory phase compared with menstruation.
Progesterone levels were associated with region-specific differences in gray matter volume and cortical thickness that varied by phase. During the periovulatory phase, higher progesterone levels correlated with greater volume in cerebellar regions. During menstruation, associations were observed in frontal regions, including areas involved in emotion and decision-making. Cortical thickness showed phase-dependent associations across parietal, temporal, and frontal regions.
Estradiol showed fewer and less consistent associations with structural measures.
Predefined analyses of the amygdala and hippocampus did not remain statistically significant following correction for multiple comparisons, suggesting that hormone-related structural variation may extend beyond traditionally studied regions.
To explore potential mechanisms, the researchers compared structural findings with maps of hormone receptor distribution. Brain changes were more strongly aligned with regions with higher progesterone receptor density, supporting a possible receptor-linked pattern of neuroplasticity.
Although mood symptom scores were slightly higher during menstruation, they were not associated with hormone levels in this cohort. The researchers noted that the findings were based on a small, healthy sample and did not include the luteal phase, which may limit generalizability.
Overall, the results suggest that progesterone may play a key role in hormone-related structural variation in the brain, with effects that differ between menstrual phases.
The researchers reported no competing interests.
Source: eBioMedicine
