Estradiol during (analogue-) trauma: risk- or protective factor for intrusive re-experiencing?

Intrusions, a key symptom of posttraumatic stress disorder (PTSD), can occur as classically conditioned responses to trauma-related cues, both in the form of images and pain sensations. Women are more vulnerable to experiencing intrusions, and gonadal hormones may underlie this sex difference. Yet so far, particularly estradiol’s influence on intrusions is unclear, as PTSD-symptom studies suggesting a vulnerable window for intrusions during the high estradiol-progesterone phase diverge from fear-conditioning studies suggesting a protective role of estradiol. Here, we aim to address this discrepancy and examine the effects of estradiol on intrusions while also considering stress as potential moderator.Forty free-cycling women participated in an ecologically informed trauma-pain-conditioning (TPC) paradigm, using trauma-films and pain as unconditioned stimuli. Predictors were salivary estradiol and stress indexed by salivary cortisol and self-reported state-anxiety during TPC. Outcomes were film- and pain-intrusions occurring during daily-life in the week following TPC and a memory-triggering-task in response to conditioned stimuli 24h after TPC.Estradiol yielded time- and stress-dependent effects on film-intrusions during daily-life: women with higher estradiol showed initially greater probability of experiencing film-intrusions, switching to lower probability toward the end of the week. This late protective effect of estradiol on film-intrusions only held for higher state-anxious women. In contrast, estradiol showed consistent protective effects on pain-intrusions during daily-life and memory-triggering-task. Together, these data suggest that high estradiol during trauma may shield women from long-term audiovisual trauma intrusions, as well as from pain-intrusions, and thereby possibly constitute a protective factor for PTSD and potentially also for chronic pain.