Moniek Hutschemaekers

68 Chapter 4 administered to healthy participants prior to threat exposure was found to reduce fear, enhance reward sensitivity, and promote social approach motivation (Bos, Panksepp, et al., 2012; Enter et al., 2014; Terburg et al., 2016). Eye-tracking and electrophysiological studies by our group showed that, when administered to women with SAD, testosterone reduced automatic threat bias to angry faces (Enter, Terburg, et al., 2016; van Peer et al., 2017), diminished social avoidance, and promoted prosocial behavior, including approach towards angry faces (Enter, Spinhoven, et al., 2016). Although preliminary, these findings provide promising evidence that testosterone administration prior to exposure therapy enhances the treatment’s efficacy by promoting social approach, one of its main goals (Enter et al., 2018; Hutschemaekers et al., 2020). Given its profound role in the regulation of social motivational behavior, in the present proof-of-concept study we test the augmentation effects of testosterone on exposure in women coping with SAD in a randomized clinical assay, comparing a single testosterone-enhanced session (0.50 mg) with a placebo-supplemented session. To assess the transfer of testosterone-induced effects, the participants engaged in a similar but unenhanced exposure session one week later. We hypothesized that, compared to the placebo group, testosterone-enhanced exposure would induce steeper reductions in subjective fear during the repeated exposure session, as an index of retention of extinction learning during session 1 (Craske et al., 2008; Foa & Kozak, 1986a; Foa, Huppert, & Cahill, 2005). In addition, we verified whether testosterone supplementation would affect self-reported pre-to-post-treatment social anxiety symptoms. Finally we explored physiological effects of acute testosterone administration by assessing within-session Heart rate (HR). Given the recent insight into the moderating effects of endogenous testosterone on exogenous testosterone (Carré et al., 2015a; van Honk et al., 2011; Welling, Moreau, Bird, Hansen, & Carré, 2016) and the efficacy of exposure treatment for SAD in particular (Hutschemaekers et al., 2020), we explored endogenous testosterone as a moderating factor in our analyses. Methods and Materials Participants Participants were recruited from an outpatient clinic specializing in the treatment of anxiety disorders, from the Radboud University Nijmegen, and from the community from 2017 through 2019. Inclusion criteria were: 1) woman, 2) age: 18-45 years, 3) primary diagnosis of SAD (as assessed with the Mini International Neuropsychiatric Interview (MINI; (Sheehan et al., 1998)), with a predominant fear of public speaking, and 4) score > 30 on

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