80 Chapter 4 in hypogonadal mice and human males, while long lasting effects of endogenous testosterone may upregulate its expression (Sader et al., 2005). The observed effects of exogenous testosterone on fear levels did not generalize to SAD symptoms. Although we extend previous observations that a single dose of testosterone can affect threat-approach behavior in SAD in an experimental context (Enter, Spinhoven, et al., 2016; Enter, Terburg, et al., 2016), to fear-reactivity in a clinical context, we do not observe an effect on clinical outcomes. This may be a result of the fact that our symptom outcome measure (SPS) only has one item measuring speech anxiety. We recommend future studies to use a measure more sensitive to changes in speech anxiety. On the other hand, research testing other pharmacological enhancers demonstrated that repeated doses yielded better exposure outcomes than did a single dose (Rosenfield et al., 2019; Smits et al., 2020). So, future investigations comprising more testosterone-enhanced sessions are necessary to establish whether testosterone can improve SAD symptoms. As to the strengths of our study, we can say that with a comparative randomized clinical assay we were able to establish that the administration of a single dose of testosterone was safe and tolerable; there were no adverse events or augmentation-related drop-out. Moreover, by comparing effects in two successive sessions, we were able to examine the direct effects of the enhancement and their transfer in a relatively quick and cost-effective manner. However, since we only included women because the administration method we used has as yet only been applied in women (Tuiten et al., 2000), we cannot say whether our findings will generalize to men. Also, due to inclusion restrictions (e.g. birth control types, pregnancy) and because women with relatively low endogenous testosterone were relatively underrepresented, it remains to be tested whether findings generalize to a broader group and replication in a larger, more varied sample is needed. Furthermore, although all our participants met the SAD criteria, their baseline severity scores were somewhat lower than those reported in other exposure enhancement studies (Guastella et al., 2007; Hofmann et al., 2019; Smits et al., 2020). Even though our findings show that exogenous testosterone already exerts effects in a population with relatively mild symptoms, it needs to be shown whether they generalize to more severely impaired populations. To conclude, testosterone-augmented exposure differentially affects in-session fear levels, partly depending on baseline testosterone levels of individuals with SAD. It reduced self-reported peak fear levels in individuals with low baseline testosterone, and increased reactive patterns in individuals with high baseline testosterone. Because both patterns may be relevant for long term extinction learning, we hope this study inspires investigation of the longer-term effects of repeated testosterone-enhancements in SAD.
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