Sex hormones adjust “sex-specific” reactive and diurnal cortisol profiles

Abstract

Sex differences in stress hormone functions are presumed to depend on sex hormones. And yet, surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone, estradiol, and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis. In this methodological study of 204 healthy adults (60 men), we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes. Reactive cortisol was sampled using 6 saliva samples measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women. Diurnal cortisol was sampled over two days at (1) awakening, (2) 30-min thereafter, (3) 1400 h, (4) 1600 h, and (5) bedtime. Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment. Repeated-measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones. Results revealed that men had higher reactive cortisol than women in unadjusted analysis, but this sex difference was attenuated when adjusting for sex hormones. While diurnal cortisol showed no sex differences in unadjusted models, adjusting for sex hormones revealed that women have higher morning cortisol. Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implications for social and affective neuroscience. In summary, our results reveal that adjusting for sex hormones alters "sex-specific" reactive and diurnal cortisol profiles.

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

“…This homeostatic mechanism might override any association that pre-TSST progesterone has with post-TSST cortisol levels in men. It is important to note, however, that Juster et al (2016) found a negative correlation in men between progesterone and cortisol response just as we had with women. The men in that study differed from the present study in that they were generally older (average age, 39) and more diverse in drug use and mental health history.…”

“…First, we report the novel finding that testosterone levels in men were negatively correlated with salivary cortisol response to the TSST. While Juster et al (2016) reported no correlation between pre-TSST testosterone and post-TSST cortisol, their sample size of men was smaller (n=60) suggesting that the study may have been underpowered. The correlations we observed were -0.3 and -0.26 which, with a sample size of 147 men, is considered to be in the moderate range.…”

“…In men, acute doses of progesterone suppressed cortisol response to the TSST (Childs et al, 2010b). Recently, Juster et al (2016) reported that sex differences in cortisol response to the TSST were attenuated when analyses were adjusted for baseline progesterone, testosterone and estradiol levels. Although their sample of women was large (n=144), it comprised a group with heterogeneous hormonal status (normal cycling, post-menopausal, or on hormonal contraceptives), many of whom had current or past psychiatric histories.…”

“…First, we hypothesized that men will have a greater ACTH and cortisol response than women to the TSST. Based on extensive preclinical literature and preliminary human studies, we also hypothesized that sex hormone levels at the onset of stress will negatively correlate with HPA axis hormone response in both men and women (Handa and Weiser, 2014; Juster et al, 2016). …”

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).…”