Post-traumatic Estradiol Administration and Care Evaluation (PEACE)

One in five U.S. females experience sexual assault in their lifetime, and CMSP and PTSD are common, costly, and difficult-to-treat outcomes. Despite the substantial public health burden of these conditions, few therapeutics exist to prevent CMSP or PTSD after SA. Preclinical and observational studies suggest that early administration of 17β-estradiol (E2) following traumatic stress may reduce the risk of developing CMSP and PTSD, with evidence indicating that the timing of E2 exposure relative to the traumatic event is critical. However, no randomized clinical trial has yet evaluated whether early E2 administration can prevent these outcomes following SA. To address this gap, this pilot, randomized, double-blind, placebo-controlled trial will enroll 30 individuals assigned female at birth, aged 18 to 45 years, who experienced SA within the prior 120 hours. After screening and confirmation of eligibility, participants will be randomized 1:1 to receive either a single oral 6 mg dose of encapsulated E2 (three 2 mg tablets) or an identical placebo within 120 hours of the SA. Blood samples will be collected immediately before study drug administration and again 90 to 120 minutes afterward to assess circulating E2, cortisol, inflammatory mediators (including IL-6, IL-8, IFN-γ, IL-10, and TNF-α), and RNA expression. Participants will complete standardized assessments of pain, PTSD symptoms, and related clinical outcomes at baseline and at Week 2, Week 6, and Month 3 following enrollment. The Month 3 visit will include a final blood collection. The primary objectives of this pilot study are to evaluate the feasibility, acceptability, and tolerability of administering early E2 following SA. Secondary and exploratory objectives include characterizing the biological response to E2 administration and obtaining preliminary estimates of its effects on CMSP and PTSD symptoms. Findings from this study will inform the design and implementation of a future fully powered efficacy trial. The selected E2 dose is based on observational findings demonstrating that peritraumatic circulating E2 concentrations above approximately 100 pg/mL are associated with a lower risk of CMSP and PTSD, together with the established safety profile of comparable oral E2 doses in other clinical settings.