Scientists have found that taking oral contraceptives can long-term alter the brain’s response to safe situations, increasing so-called “contextual fear.” These findings come from a study published in the journal Neuropsychopharmacology.

The experiment involved 147 healthy adults: men, naturally cycling women, and women who were current or former users of oral contraceptives. Participants completed a two-day fear acquisition and extinction protocol, during which researchers measured skin conductance responses and brain activity. The results showed that both current and former contraceptive users exhibited heightened fear responses in safe contexts compared with women who had never taken these medications.

The effect was particularly pronounced in women taking high-dose ethinylestradiol contraceptives. Neuroimaging revealed that the increased fear responses were accompanied by reduced activity in the hippocampus and ventromedial prefrontal cortex—brain regions responsible for recognizing safe contexts and suppressing anxious reactions.

The study authors note that external hormones may disrupt the brain’s ability to extract “safety signals” from the environment. Importantly, this effect persists even after discontinuing contraceptive use. According to the researchers, these findings help explain why anxiety disorders and post-traumatic conditions are more prevalent in women than in men.