Estrogen for the treatment of Borderline Personality Disorder/Complex Post-Traumatic Stress Disorder

Overview & Rationale: Borderline Personality Disorder (BPD) is a serious and highly prevalent (5.9%) psychiatric disorder. BPD sufferers experience severe emotional instability, social and occupational dysfunction, and engage in chronic self-mutilation and suicidal behaviours, with associated high levels of mortality, morbidity, and health service use. BPD patients are a complex group that are challenging to treat. Current psychological treatments are expensive and difficult for BPD patients to access, and there is currently no clearly designated pharmacotherapy. Underpinned by psychosocial causes, the pathogenesis of BPD is only now beginning to be understood. Childhood trauma is reported in most patients (>80%) and is linked to abnormalities in the development of the hypothalamus-pituitary-adrenal stress axis and, consequently, abnormalities in the hypothalamus-pituitary-gonadal axis. Both neuroendocrine axes have been reported as abnormal in BPD, indicating the neuroendocrine system as a potential therapeutic target for BPD symptoms. Significantly, cyclical fluctuations in ovarian hormones affect emotional and cognitive behaviours relevant to BPD. We propose to conduct a 12-week, double blind, placebo controlled two arm trial of i.) transdermal estradiol gel 2 pumps (1 pump =1.25mg gel = 0.75mg estradiol, total = 1.5mg daily estradiol) vs ii.) placebo inactive gel 2 pumps daily (in addition to treatment as usual), in a total of 72 women with BPD/CPTSD (48 for the estradiol arm and 24 for the placebo arm) over 12 weeks. Primary Aim: To determine whether estradiol is effective in treating symptoms of BPD/CPTSD. Secondary Aims: To determine if estradiol has effect on specific BPD/CPTSD symptom domains including: a) social - emotional regulation; b) cognition, including memory, decision making and executive functioning; c) concomitant mood and quality of life; and d) biological markers