Exogenous testosterone attenuates the integrated central stress response in healthy young women

Animal research has shown that the androgen steroid testosterone, the end product of the hypothalamic-pituitary-gonadal (HPG) axis, down regulates the integrated stress response at multiple levels. These effects have been demonstrated at the level of the amygdala and the bed nucleus of the stria terminalis, and along the different nodes of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was designed to assess effects of exogenous testosterone upon reactivity of the autonomic nervous system and modulation of the acoustic startle reflex in humans. Twenty healthy female participants received double-blind, placebo-controlled sublingual administrations of .5mg testosterone. Measurements were made of phasic electrodermal activity, cardiac responses, and startle reflexes to acoustic probes while participants were exposed to pictures with strongly aversive, neutral, or positive content. Subjective reports of mood and picture evaluations were also obtained. Results support the hypothesis of a generally decreased responsiveness of the stress system by showing reduced skin conductance responses as well as reduced affective startle modulation in anxiety-prone participants after administration of testosterone. Candidate neurobiological mechanisms of action are outlined and discussed, and it is argued that androgens promote dynamic regulation of the stress system through actions upon central neuropeptidergic pathways that control corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) expression. The present findings highlight the importance of further investigation of the possible role of the HPG axis in disorders that are associated with HPA axis dysfunctions.