Brain dynamics predict oral contraceptive treatment duration

Abstract

Oral contraceptives are used by millions of women worldwide, yet their cumulative effects on the female brain remain poorly understood. We analyzed resting-state fMRI from 192 women (never, current, and past users) using brain-dynamics metrics that quantify information transfer across spatiotemporal scales. Duration of use was associated with a progressive, age-independent modulation of brain dynamics: prolonged use was related to restricted local synchronization but enhanced information flow across scales. Machine learning predicted individual duration of use from brain dynamics, and node-level classifiers distinguished users from never-users based on a spatially distributed cortical pattern spanning multiple functional networks, most clearly detectable in long-term users. In past users, these associations were inverted in sign, scaling with prior duration rather than returning to the never-user baseline, suggesting active reorganization following cessation. Together, these results indicate that cumulative oral contraceptive exposure acts as a neuromodulator of information processing.