Associations between past and current use of oral contraceptives and fear regulation.

Abstract

Background: Low endogenous estradiol (E2) levels can occur naturally during menstruation or through oral contraceptive (OC) use. Such low levels have been suggested as vulnerability factors for impaired fear extinction memory recall. Although hormonal contraceptives have been linked to enduring psychological outcomes, their possible long-term relevance for extinction memory remains underexplored.

Methods: This study aimed to replicate findings linking OC use with altered extinction recall, and to examine potential long-term associations and neural correlates. To do so, a validated fear protocol (day 1: fear conditioning, extinction learning; day 2: extinction recall, fear renewal) was administered to 147 healthy adults. Psychophysiological (skin conductance responses; SCRs) and neural between-group differences were examined across the protocol using two types of groupings: (1) E2-based groups (men, current OC users, women in the early follicular phase, women in the pre-ovulatory phase) and (2) OC-history-based groups (men, current OC users, never OC users, past OC users).

Results: During extinction recall, higher SCRs were found in current OC users relative to pre-ovulatory women (grouping 1) and to never users (grouping 2). Among current OC users, SCRs during extinction recall correlated with hippocampus, dorsal-rostral anterior cingulate cortex (ACC), and ventromedial prefrontal cortex (vmPFC) activations. Exploratory analyses revealed that past OC users who were in the early follicular phase exhibited SCRs as high as current users.

Conclusion: These findings highlight impaired extinction recall in current OC users, with vmPFC, ACC and hippocampal involvement. Past OC use may carry lasting associations with fear dysregulation, particularly under low-E2 states.