Hypothalamic–pituitary–adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones

Abstract

Summary Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the TSST than do women during the follicular phase of the menstrual cycle.

Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex

“…This is in agreement with population studies and a number of clinical studies showing that men experienced greater HPA-axis activity than women in response to various laboratory stressors, including examination stress, pain, cognitive tasks, and public speaking (Stephens et al, 2016; Kirschbaum et al, 1992; Zimmer et al, 2003; Kirschbaum et al, 1999; Kudielka et al, 1998; Seeman et al, 2001). In this study, only women demonstrated reduced activity in mPFC and hypothalamic-hippocampal connectivity dependent on cortisol.…”

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress

“…A parsimonious explanation of this coupling is that participants found the TSST (or its modification) to invoke a challenge more than a stressor response. Robust coupling across axes fits with the emerging dual-axis models (Marceau et al, 2015; Susman, Peckins, Bowes, & Dorn, 2017; Harden et al, 2016; Juster, Raymond, Desrochers, Lupien, 2016; Stephens, Mahon, McCaul, & Wand, 2016), and with an interpretation of the TSST as both a stressor and a challenge (Mehta, Jones, & Josephs, 2008; Mehta, Welker, Zilioli, & Carre, 2015; Denson, Mehta, & Tan, 2013; Salvador, 2005). It is more difficult to integrate with models that describe inhibition of one axis by the other (Viau, 2002; Koob & LeMoal, 2001), such as studies which describe androgens as a stress buffer, DHEA as an anti-glucocorticoid (Kalimi et al, 1994), or which find unique high testosterone/cortisol reactivity ratio findings (Glenn et al, 2011; Huovinen et al, 2009; Welker et al, 2014).…”

Hormonal underpinnings of status conflict: Testosterone and cortisol are related to decisions and satisfaction in the hawk-dove game

“…This pattern suggests that playing the hawk-dove game with another man may have caused men's cortisol and testosterone responses to resist circadian decline. This general pattern resembles sex differences in endocrine reactivity to social-evaluative stressors such as the Trier Social Stress Test (TSST); men tend to show stronger cortisol stress responses to the TSST compared to women (Stephens et al, 2016). The testosterone response pattern in men is also consistent with the challenge hypothesis (Wingfield et al, 1990;Archer, 2006).…”