Inter- and intra-individual trajectories of brain sex in different neuroendocrine profiles

Abstract

Sex hormone fluctuations modulate structural and functional brain dynamics, yet little is known on how sex steroid levels map onto the expression of sex differences in the brain. Here, we trained machine learning models for brain sex classification based on magnetic resonance imaging regional volumes in cross-sectional data of N = 1090 individuals (50% females, age matched). Applied to densely sampled data of one male and two females in different hormonal states (naturally cycling, oral contraceptive user, pregnancy), we associated inter- and intra-individual fluctuations in brain sex with neuroendocrine profiles. We found lower variation in brain sex across scan sessions in the male compared to the female subjects. Oral contraceptive use was associated with a more female-like brain, while opposite brain sex trajectories emerged across menstrual cycle phases and pregnancy trimesters. Overall, our findings suggest that changes in brain sex capture hormone-related plasticity over time in densely sampled individuals.