Oestradiol treatment for mood stabilisation in borderline personality disorder

To the Editor

In women, low and fluctuating levels of oestradiol are shown to underpin vulnerability to stress-related psychiatric disorders, as well as treatment response (Maeng and Milad, 2015), though studies rarely control for menstrual cycle phase, oral contraceptive use or basal hormone levels.

Alice, a 21-year old patient, was diagnosed with borderline personality disorder (BPD) 3 years previously. BPD is a complex, severe and highly stigmatised psychiatric illness that can result from childhood trauma plus genetic vulnerability, evoking a stress response that promotes pathophysiological processes.

Alice presented at our tertiary clinic for women’s mental health with severe emotional dysregulation, self-harm and suicidality. Current medications were quetiapine immediate release (IR) 200 mg/day plus extended release (XR) 50 mg twice daily, lamotrigine 200 mg twice daily and duloxetine 120 mg/day.

In line with emerging evidence of oestradiol’s psychoprotective effects (e.g. Kulkarni et al., 2015), our Professor of Psychiatry (J.K.) in consultation with our Endocrinologist (specialising in psychoneuroendocrine aspects of women’s mental health) commenced Alice on daily oral oestradiol 1.5 mg/nomegestrol acetate 2.5 mg, and 1 month later added transdermal oestradiol (titrated to 37 µg/day). Adverse effects were monitored fortnightly.

At 8 weeks of treatment, substantial improvements in Alice’s overall symptom severity (7-point change, Zanarini Rating Scale for Borderline Personality Disorder), affect dysregulation (14-point change, Difficulty in Regulation of Emotions Scale) and self-reported negative thoughts, emotions and behaviours (17-point change, Borderline Evaluation of Severity over Time) were observed. Due to irritant contact dermatitis of increasing severity, transdermal oestradiol was substituted with oral oestradiol valerate 1 mg/day and then increased to 2 mg/day to improve response.

Over a 12-month period of treatment and monitoring, Alice reports her mood to have stabilised with a significant reduction in anger. Most notably, her previously prominent suicidal tendencies have been near absent for 9–12 months – even in the context of worsening life stresses. A sustained dose reduction of quetiapine (IR) to 125 mg/day has also been achieved.

This is the first case to report improvement of BPD symptoms with oestradiol use. While little is currently known about oestradiol’s role in modifying neural function in BPD, oestrogen levels have been demonstrated to play a critical role in vulnerability to stress and fear responses in extrapolative post-traumatic stress disorder research (Glover et al., 2015). Co-administration with a progestin (as we did with nomegestrol acetate) can reduce risks associated with unopposed oestradiol on reproductive tissue. Oestrogen modulation holds promise in advancing treatment of BPD, and clinical research to examine efficacy and dose-dependent effects is now warranted.