(PS2-A1) The Association of Endogenous Estradiol and Subjective Distress Ratings in Women Receiving Exposure Therapy for Anxiety Disorders

Estradiol, a sex hormone involved in regulating menstrual cycles, may moderate fear extinction. In prior research with female rats and women, low levels of estradiol have been associated with impaired extinction to a conditioned stimulus, whereas high levels of estradiol have been associated with greater extinction recall.

It is important to replicate these findings in a clinical population, as the bulk of prior research on estradiol and fear extinction involved healthy participants without anxiety disorders and laboratory-based extinction paradigms, which may not represent exposure therapy for anxiety in clinical practice. To address this literature gap, we examined whether endogenous estradiol was associated with subjective distress levels during exposure therapy for anxiety disorders.

It was hypothesized that those in the high estradiol group (based on median split) would display better fear extinction gauged by lower distress ratings than would those in the low estradiol group. Participants were 24 women with a primary diagnosis of a DSM-IV anxiety disorder who were in routine exposure therapy at an anxiety specialty clinic. Estradiol levels were assessed using saliva samples collected in sterile vials directly prior to an exposure therapy session.

Participants used the Subjective Units of Distress Scale (SUDS) to rate their distress before (pre) and after (post) the exposure session, as well as their peak distress level during the session. After a brief delay, subjects rated their SUDS again (the extinction “recall” rating) after being reintroduced to the feared stimulus. Data collection is ongoing (current n = 24, target N = 30, data collection will be over by April 2023); thus, current results are preliminary. A series of 2 (group: high or low estradiol) x 3 (time: pre, post, and peak SUDS) repeated-measures analysis of variance showed a significant effect of time, F(2, 46) = 18.48, p < .001, partial η2= 0.45, suggesting an improvement in subjective distress over the course of the exposure session, but there were no significant differences between those with high or low estradiol levels (interaction term F(2, 46) = 0.09, p = 0.91, partial η2 = 0.004). There were no main or interaction effects found for pre-post SUDS or post-recall SUDS (all Fs < 1.19, all ps > 0.05). Given the limitations of median splits, these data were analyzed in a series of hierarchical multiple regression analyses, with estradiol level (continuous variable) as a predictor and post, peak, and recall SUDS (separately) as the dependent variables, controlling for pre SUDS. Results revealed that estradiol predicted peak and recall SUDS at a trend level (Peak: estradiol coefficient, t(22) = -1.82, p = 0.08, step 2, ΔR2 = 0.12, p = 0.08; Recall: estradiol coefficient, t(21) = -1.69, p = .106, step 2, ΔR2 = 0.10, p = .106). These findings support the hypothesis that higher estradiol may be associated with lower subjective distress levels of women with anxiety disorders receiving exposure therapy; however, further replication is needed. Limitations include a small N consisting of mainly white, non-Hispanic/Latinx women, so future research would benefit from a larger and more diverse sample to widen the generalizability of these findings in women, a historically marginalized group.