What’s happened here to cause these physiological responses? Your heart rate and blood pressure have skyrocketed, you feel shaky, maybe in disbelief, with thoughts racing through your mind. The stress system is very complex, so I’ll cut to the main neuroendocrinal point for this blog, which is best described with an example. Dysregulation of this system (both hyper and hypo-activation) can lead to a marked disruption in body homeostasis leading to clinical complications. Though, as we know, returning to a normal state can take quite some time.
Follow-up analyses revealed that the effects of testosterone among high-dominance men were also seen on two specific subscales of negative affect, fear and hostility (Table S6, Figure S5). In each graph, "Pre-TSST" was measured after giving instructions for the social-evaluative stress task but before beginning the task and is therefore a measure of anticipatory negative affect. For men high in trait dominance, testosterone increased cortisol AUCI compared to placebo; no differences were evident for low trait dominant men (Figure 3; see Supplemental Materials for reactivity and recovery analyses, Figure S4). No differences in pre-TSST cortisol or baseline affect were found between treatment groups or in exploration of interactions between treatment group and trait dominance (see Supplementary Materials). Testosterone administration resulted in testosterone levels that exceeded the EIA kits’ maximum (5250 pg/mL) in 34.4% of samples within the testosterone group (17% of all samples; no samples in placebo condition were above threshold).
ELK was partially supported by National Institute on Aging Grant T32 AG to The Pennsylvania State University. This research was supported by National Science Foundation grants awarded to PHM (# ) and to WTH and UM (# ). Thus the effects reported here may depend on estradiol conversion, but future research must rigorously test this dependency in humans by blocking testosterone conversion to estradiol or antagonizing estrogen receptors. For example, some of testosterone’s effects within the central nervous system depend on local conversion to estrogen metabolites such as estradiol (Naftolin, 1994). Future work must ensure testosterone’s causal effects are robust at naturally occurring concentrations, which could be accomplished by blocking gonadal endocrine functioning prior to administering testosterone to normal physiological ranges (Goetz et al., 2014).
The placebo gel contained the same inactive ingredients as the testosterone gel; the lack of testosterone was the only difference between the gels. The testosterone gel (AbbVie, Chicago, IL) consisted of a 150-mg dose of testosterone in addition to pharmacologically inactive ingredients (see Supplemental Materials). A laboratory member uninvolved in data collection prepared the envelopes prior to the start of data collection, thus the experimenter in the laboratory session never knew whether the vial contained testosterone or placebo, or to which blinding condition the participant was assigned. These blinding conditions were implemented to control for the expectancy effects (i.e., ‘conventional wisdom’) of receiving testosterone (Eisenegger et al., 2010). Participants were given a sealed enveloped which either revealed that the gel was testosterone or placebo – a single-blind condition – or simply stated that he had an equal chance of receiving testosterone or placebo – a double-blind condition. Upon arrival at the session, experimenters obtained informed consent from the participant (see Figure 1 for a study timeline of saliva sampling and self-report data collection). Interested parties were screened for medical conditions that would prevent participation in the study, including immune, endocrine, neurological, or mental health conditions, and alcohol or drug abuse (see Supplemental Materials).
Zinc, vitamin D, magnesium, and omega-3 fatty acids are especially important for testosterone production. A nutrient-rich diet provides the building blocks for hormones and reduces inflammation. Low testosterone increases fatigue, depression, and irritability, making everyday stressors feel heavier and harder to handle. Chronic stress lowers testosterone, which then reduces resilience to stress. The relationship between stress and testosterone is not one-directional—it is a vicious cycle.
This prior research was conducted on women using sublingual testosterone and so may have questionable value for experimental studies involving topical testosterone in men. Further, estradiol administered to men has been shown to increase HPA-axis responses to stress (Kirschbaum et al., 1996). In animal research the amygdala is a key neural component that promotes HPA responses to stress (Herman et al., 2005), with limited work suggesting it may influence human responses well (Dedovic et al., 2009). Trait prestige levels did not interact with T/P to predict cortisol levels (Tables S4). In order to confirm interpretations of the multilevel models of the cortisol response, we conducted a GLM analysis on area-under-the-curve with respect to increase (AUCI), a measure of cortisol reactivity that takes into account all four samples (Pruessner et al., 2003). The average intra-assay coefficients of variation (CVs) were 4.68% (cortisol) and 6.55% (testosterone); the inter-assay CVs were 14.8% (cortisol) and 16.1% (testosterone) averaged across low and high control samples. Saliva samples were assayed in duplicate for cortisol and testosterone in our laboratory using commercially available enzyme immunoassay (EIA) kits (DRG International; see Supplemental Materials for details).