Hormonal contraception and SSRIs influence on oxytocin and cortisol reactivity to stress in patients with borderline personality disorder

BackgroundBorderline personality disorder (BPD) involves emotional instability and stress sensitivity linked to oxytocinergic and HPA-axis dysregulation. This study examined oxytocin and cortisol responses to acute psychosocial stress and the modulatory effects of SSRIs and hormonal contraception. Methods93 female participants (45 with BPD with/without SSRIs and 48 healthy controls) underwent the Trier Social Stress Test. Linear and generalized linear mixed-effects models were applied to assess time, group, and hormonal contraception effects, and their interactions. ResultsDuring the stress task, both BPD groups reported significantly higher subjective anxiety and anger than controls. All participants showed increased salivary oxytocin (OXT) during stress anticipation, but post-task trajectories diverged: BPD participants without SSRIs exhibited a sharp OXT decline, whereas those on SSRIs mirrored the stable trajectory of controls. Hormonal contraception reversed the OXT decline in untreated BPD participants, resulting in a progressive increase during recovery. Cortisol (CORT) analyses revealed hyporeactivity in BPD participants without SSRIs, a pattern unaffected by hormonal contraception. A significant three-way interaction indicated that higher OXT levels were associated with higher CORT concentrations during late recovery specifically in the BPD SSRI group, a relationship that was marginal in untreated patients and absent in controls. ConclusionsOur findings confirm that neuroendocrine dysregulation in BPD is context-dependent and sensitive to pharmacological modulation. The ability of SSRIs and hormonal contraception to influence stress-response patterns, despite limited efficacy on core symptoms, highlights the importance of controlling for medication and hormonal status in future BPD biomarker research.