Kajantie E, Phillips DIW. The effects of sex and hormonal status on the physiological response to acute psychosocial stress. Psychoneuroendocrinology 31: 151-178

University of Helsinki, Helsinki, Uusimaa, Finland
Psychoneuroendocrinology (Impact Factor: 4.94). 03/2006; 31(2):151-78. DOI: 10.1016/j.psyneuen.2005.07.002
Source: PubMed


Whether one is male or female is one of the most important determinants of human health. While males are more susceptible to cardiovascular and infectious disease, they are outnumbered by women for many autoimmune disorders, fibromyalgia and chronic pain. Recently, individual differences in the physiological response to stress have emerged as a potentially important risk factor for these disorders. This raises the possibility that sex differences in prevalence of disease could at least in part be explained by sex differences in the nature of the physiological response to stress. In a psychophysiological laboratory, the autonomic nervous system response can be provoked by many different stressors including physical, mental and psychosocial tasks, while the hypothalamic-pituitary-adrenal axis (HPAA) response seems to be more specific to a psychosocial challenge incorporating ego involvement. The responses of both systems to different psychosocial challenges have been subject to extensive research, although in respect of sex differences the HPAA response has probably been more systematically studied. In this review, we focus on sex differences in HPAA and autonomic nervous system responses to acute psychosocial stress. Although some differences are dependent on the stressor used, the responses of both systems show marked and consistent differences according to sex, with the phase of the menstrual cycle, menopausal status and pregnancy having marked effects. Between puberty and menopause, adult women usually show lower HPAA and autonomic responses than men of same age. However, the HPAA response is higher in the luteal phase, when for example post stress free cortisol levels approach those of men. After menopause, there is an increase in sympathoadrenal responsiveness, which is attenuated during oral hormone replacement therapy, with most evidence suggesting that HPAA activity shows the same trends. Interestingly, pregnancy is associated with an attenuated response of the sympathoadrenal and HPAA systems at least as assessed by biochemical stimulation. It is likely that these sex differences in autonomic function are a result of estrogen exposure which attenuates sympathoadrenal responsiveness. The HPAA is however somewhat more complex and evidence now suggests the influence of other modifiers such as arginine vasopressin (AVP) and the regulation of circulating cortisol bioavailability by corticosteroid-binding globulin (CBG). The pronounced and multi-faceted sex differences in stress responsiveness suggest that they are a product of a strong evolutionary pressure. We hypothesise that this has to a great deal been driven by the need to protect the fetus from the adverse effects of maternal stress responses, in particular excess glucocorticoid exposure. Studying this hypothesis may have a fundamental impact on our understanding about how adult health is set during early life and how adult disease could be prevented in men and women.

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    • "Beyond reproductive functions, testosterone interacts with various HPA-axis modulators (e.g., dehydroepiandrosterone antagonizes cortisol) which can contribute to multi-systemic pathophysiology (Juster et al., 2011a). For reasons explained in part by basal differences in HPG-axis functioning, men show the most pronounced differences in HPA-axis responsivity to laboratorybased stressors that elicit social-evaluative threat (Dickerson and Kemeny, 2004; Kajantie and Phillips, 2006; Kirschbaum et al., 1992). Yet for both sexes, enhanced HPG-axis activities like testosterone production are also indicative of challenge and anticipation (Chichinadze and Chichinadze, 2008; Chichinadze et al., 2012a,b), suggesting that the HPG-axis is involved in preparedness to respond for both sexes in stress paradigms. "
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    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) 1400h, (4) 1600h, 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.
    Psychoneuroendocrinology 11/2015; 63:282-290. DOI:10.1016/j.psyneuen.2015.10.012 · 4.94 Impact Factor
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    • "Author's personal copy noted that males have a stronger cardiovascular and HPA axis response to stress than females (Kajantie and Phillips 2006) and all males were in the HSC group. Therefore, it is possible that some of the lack of difference evidenced between HSC and LSC groups in cardiovascular reactivity is because of the higher expected reactivity of the HSC group due to the presence of all males in this group. "
    Journal of Child and Family Studies 10/2015; DOI:10.1007/s10826-015-0307-3 · 1.42 Impact Factor
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    • "Second, our cohort was limited to women, and therefore, it is unknown whether these associations would be observed among Chinese immigrant men. Previous studies have reported stronger associations between stress and diabetes risk in women than in men (Heraclides et al., 2012), and it has been proposed that women are more vulnerable to stress-related alterations in physical and mental health (Kajantie and Phillips, 2006). Thus, further exploration of gender-specific pathways in stress and insulin resistance is warranted. "
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    ABSTRACT: Background: Chinese immigrants experience increased chronic disease risk following migration to the US. Although the impact of lifestyle changes (e.g., diet) on disease risk has been extensively studied, associations of psychosocial stress and disease risk have attracted less attention. Thus, the objective of the present study was to examine associations between stress and insulin resistance in foreign-born Chinese American women. Methods: From October, 2005 to April, 2008, 423 women recruited from southeastern Pennsylvania completed questionnaires reporting stressful life events. Blood samples were analyzed for fasting insulin and fasting glucose levels, which were used to estimate insulin resistance according to the homeostasis model assessment (HOMAIR). Results: In logistic regression analyses, a greater number of negative life events was associated with insulin resistance (OR=1.17, 95% CI=1.02-1.34), controlling for age, level of acculturation, marital status, body mass index, and waist circumference. Similarly, greater negative life event impact ratings were also associated with insulin resistance (OR=1.08, 95% CI=1.01-1.16) controlling for relevant covariates. Conclusions: This is one of the first studies to examine associations between psychosocial stress and insulin resistance in Chinese immigrant women. These findings contribute to a growing body of literature on stress and diabetes risk in an immigrant population.
    09/2015; 2:563-567. DOI:10.1016/j.pmedr.2015.06.013
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