Females with BPD experience severe and rapidly shifting emotional, interpersonal, and behavioral symptoms, often co-morbid with mood and anxiety disorders [1, 3]. Recent evidence highlights the role of fluctuating ovarian hormones in these rapid shifts and the severity of symptoms related to BPD. [2, 8,9,10,11] Here, we investigated the impact of ovulation-suppressing contraceptives on behavioral and functional difficulties in those with and without a BPD diagnosis to explore whether contraceptives that suppress ovulation, and with it the fluctuations in estrogen and progesterone, may impact the manifestation and severity of psychiatric outcomes related to BPD.
In the current study, the use of ovulation-suppressing contraceptives was not associated with the severity of behavioral and functional difficulties either at admission and discharge or change in symptom severity pre- to post-treatment. Although females with a co-morbid BPD diagnosis were more likely to use ovulation-suppressing contraceptives compared to females without, the association did not remain significant after adjusting for age and primary diagnosis. This finding is consistent with an earlier study reporting higher levels of BPD symptoms in females using oral contraceptives [11]. However, we cannot assess the directionality of this association with our current sample, since the participants who were on ovulation-suppressing contraceptives had them prescribed before initiating the residential treatment and we do not have any information as to whether they were prescribed ovulation-suppressing contraceptives to manage their behavioral symptoms or for other reasons (i.e., birth control, menstrual regulation).
The reports regarding whether hormonal contraceptives increase or decrease the risk of mental health disorders are mixed [12,13,14,15,16]. However, recent evidence suggests that the association between hormonal contraceptives and mental health outcomes may depend on individuals’ psychiatric history [14]. While some studies reported mood-related disturbances as a side effect of contraceptives in the general population [12, 13], oral contraceptive pills were shown to be effective in the treatment of PMDD and premenstrual worsening of depressive symptoms in females with MDD [23,24,25,26]. Moreover, a recent meta-analysis reported that the use of hormonal contraceptives was associated with a decrease in depressive symptoms in females with pre-existing psychiatric disorders but an increased risk of depression in females without any history of psychiatric disorders [14]. Therefore, in addition to examining the associations between BPD, ovulation-suppressing contraceptives, and psychiatric outcomes, we sought to explore the interaction between ovulation-suppressing contraceptives and BPD. As expected, a co-morbid BPD diagnosis was associated with more severe behavioral and functional difficulties, specifically increased difficulties in relationships, impulsivity, depression, anxiety symptoms, and difficulties in daily living. Importantly, we showed that ovulation-suppressing contraceptives moderated the association of BPD with difficulties in relationships, depression, and anxiety symptoms, and difficulties in daily living, such that the associations between BPD and the severity of psychiatric outcomes are more pronounced in naturally cycling females, compared to females using ovulation-suppressing contraceptives. We also observed a differential association between ovulation-suppressing contraceptives and difficulties in relationships, depression and anxiety symptoms, and daily living, depending on BPD diagnosis. Specifically, the use of ovulation-suppressing contraceptives was associated with more severe symptoms, but only in individuals without co-morbid BPD. The use of ovulation-suppressing contraceptives did not influence the associations between BPD and changes in behavioral and functional difficulties during treatment. These findings suggest that higher behavioral and functional difficulties associated with the use of ovulation-suppressing contraceptives may be less pronounced in individuals with BPD, potentially due to ovulation-suppressing contraceptives helping to regulate the rapidly shifting emotional, interpersonal, and behavioral symptoms characteristic of BPD. This aligns with recent evidence showing that the use of hormonal contraceptives is associated with decreased psychiatric symptoms among females with pre-existing mental disorders, but an increased risk of psychiatric symptoms in females without prior mental health conditions [14]. The mechanisms behind this differential impact of ovulation-suppressing contraceptives on behavioral and functional difficulties between those with and without BPD are yet to be elucidated. One potential mechanism may be through stabilizing estrogen and progesterone fluctuations. Ovulation-suppressing contraceptives could reduce emotional reactivity by preventing estrogen and progesterone fluctuations [27] or, specifically, the prevention of allopregnanolone—a metabolite of progesterone—flux during the luteal phase, which has been linked to irritability and interpersonal difficulties [9, 10]. Studies have shown that preventing the metabolism of progesterone to allopregnanolone can alleviate PMDD symptoms, suggesting that stabilizing these hormonal pathways may mitigate the emotional and behavioral symptoms seen in BPD. [20, 28,29,30] Alternatively, ovulation-suppressing contraceptives reduce testosterone levels which were shown to be elevated in those with BPD [31,32,33]. In addition to hormonal mechanisms, social determinants of health (e.g., socioeconomic status (SES), access to healthcare) can also contribute to observed differences in behavioral and functional difficulties between patients with BPD using ovulation-suppressing contraceptives and those who do not. Individuals prescribed ovulation-suppressing contraceptives may have better access to healthcare, including gynecological and psychiatric care, contributing to earlier detection and management of psychiatric symptoms.
Finally, our findings align with the hypothesis that BPD may involve a sensitivity to hormonal fluctuations similar to that observed in PMDD. Specifically, the observed moderating effect of ovulation-suppressing contraceptives on the association between BPD and difficulties may be attributed to the stabilization of progesterone and its metabolite allopregnanolone. The Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC) framework proposes that individuals with heightened sensitivity to hormonal flux, particularly surges in allopregnanolone, experience pronounced affective changes, such as irritability and interpersonal difficulties, during the luteal phase [34]. This transdiagnostic sensitivity to hormone flux may contribute to similar patterns of emotional reactivity in individuals with BPD, suggesting that the benefits of ovulation-suppressing contraceptives could be related to preventing these hormonal surges.
Although the study has numerous strengths, including a comprehensive investigation of behavioral and functional difficulties longitudinally, it is not without limitations. First, the duration of contraceptive use varied among participants, which could confound our analyzes. Second, we did not perform subgroup analyzes on different types of ovulation-suppressing contraceptives (i.e., combined oral contraceptives, progestin-only methods, etc.) due to power considerations. Third, we do not have information on the temporal history of ovulation-suppressing contraceptive use (i.e., whether patients were prescribed contraceptives before or after the manifestation of their psychiatric symptoms). It is also possible that patients who are naturally cycling may have discontinued hormonal contraceptives due to adverse mood effects, which are often associated with increased sensitivity to hormonal fluctuations across the menstrual cycle. This would suggest that the natural cycling group could represent a more hormone-sensitive subgroup, potentially leading to a stronger association between hormonal fluctuations and mood disturbances in this group compared to those on contraceptives. The younger age of patients on contraceptives, as observed in our sample, may align with this interpretation, as younger individuals may be less likely to have experienced adverse effects from contraceptives or may not have used them long enough to discontinue due to mood-related side effects. Thus, we cannot determine causality or directionality—whether BPD comorbidity predicts the severity of symptoms in those using ovulation-suppressing contraceptives and are naturally cycling, or whether ovulation-suppressing contraceptive use predicts symptom levels in individuals with and without BPD. Finally, we did not account for the menstrual cycle phase and its interaction with contraceptives, as we lacked ovarian hormone measures and menstrual cycle length information to accurately phase participants’ cycles. While hormone levels in those using ovulation-suppressing contraceptives would not provide much insight, the phase of the menstrual cycle could still influence psychiatric symptoms in naturally cycling individuals [15]. Yet, our longitudinal analyzes included measures at two time points, which to some degree account for within-subject variability due to the menstrual cycle phase.
Overall, our findings suggest that ovulation-suppressing contraceptives may help to regulate the rapidly shifting emotional, interpersonal, and behavioral symptoms in those with BPD by stabilizing estrogen and progesterone fluctuations. This opens up new avenues for treatment and highlights the need for further research to confirm these results and explore additional therapeutic options.
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