The Impact of Estradiol on the Formation of Intrusive Memories: a Double-Blind Randomized Placebo-Controlled Experimental Study in Healthy Women Using a Trauma Film Paradigm

• Applicants: Professor Dr. Stefan Roepke; Professorin Dr. Katja Wingenfeld
• Subject Area: Biological Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 573598040

Women are significantly more vulnerable than men to anxiety, trauma-related, and stress-related disorders, but the underlying biological mechanisms remain incompletely understood. Increasing evidence points to a critical role of sex hormones, particularly estradiol — the most potent natural estrogen — in this gender disparity. Low estradiol levels have been linked to heightened symptoms of depression and anxiety, while higher levels influence emotional and cognitive functions, including memory processes. Estradiol receptors are especially prevalent in brain regions involved in emotion and memory, such as the amygdala and hippocampus. These findings suggest that estradiol may not only be a marker of mental health states but could actively contribute to the development of symptoms like anxiety. Fear conditioning, a key process in the development of posttraumatic stress disorder (PTSD), also appears to be modulated by estradiol. Intrusive memories — a hallmark of PTSD — form during and after trauma exposure and are influenced by various neurobiological systems, including cortisol and noradrenaline pathways as well as autonomic regulation. Women show a significantly higher risk of developing PTSD after trauma, and initial studies have hinted at a role for estradiol in shaping how traumatic memories are formed. However, many of these insights are based on correlational data, which limit causal conclusions. To address this, experimental paradigms can be used. One such method is the analog trauma paradigm, in which healthy participants view a distressing film to simulate trauma-like conditions. This controlled setup allows researchers to observe the formation of intrusive memories over time. The present study aims to explore the impact of estradiol on intrusive memory formation using this paradigm. In a double-blind, placebo-controlled design, healthy women will be exposed to a stressful film. To differentiate the effects of estradiol on memory encoding versus consolidation, one group will receive estradiol before the film and another group afterward. A third group will receive a placebo at both time points. This design enables researchers to investigate not only whether estradiol affects memory formation but also at what stage its influence is most critical. The findings could deepen our understanding of sex-specific vulnerability to trauma-related disorders and open new avenues for preventive interventions.

• DFG Programme: Research Grants