None listed
Conditions
Brief summary
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
Interventions
Female participants, aged 18-43, will be randomised to receive transdermal estradiol 1.5mg daily gel or placebo gel, as an adjunct to treatment as usual, for 12 weeks (84 days). Participants will be asked about adherence that will be completed at every study visit.
Female participants, aged 18-60, will be randomised to receive transdermal estradiol 1.5mg daily gel or placebo gel, as an adjunct to treatment as usual, for 12 weeks (84 days). Participants will be asked about adherence that will be completed at every study visit.
Sponsors
Alfred Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 43 Years
Healthy volunteers
No
Inclusion criteria
– Age 18-43 years – Female – Primary diagnosis of BPD or cPTSD, assessed by the Zanarini Rating Scale for Borderline Personality Disorder (ZANBPD) or International Trauma Questionnaire (ITQ) – Be willing to use appropriate barrier contraceptive precaution for the duration of the study
Exclusion criteria
Known history of breast, endometrial or ovarian cancer Women aged 40 or over who have not had a normal mammogram in the last 24 months Abnormal pap smear in the last 24 months Contraindications to estradiol Current pregnancy or trying to become pregnant, History of blood clots (e.g. deep vein thrombosis, pulmonary embolism) Previous arterial thromboembolic disease (e.g. stroke) Acute, high risk of suicide such that inpatient admission is required, as determined by PI Kulkarni (psychiatrist) based on her expert clinical assessment. Taking more than 5 psychotropic medications Taking OCP that do not have 20, 30 or 35mcg estradiol component New/ planned changes to psychotropic medication/psychotherapy plans Consistent, severe substance abuse in last 3 months Smoking more than 20 cigarettes per day
Outcome results
None listed