Acute psychosocial challenge and cardiac autonomic response in women: The role of estrogens, corticosteroids, and behavioral coping styles
Introduction
Psychosocial challenges induce robust neuroendocrine responses mainly involving the activation of the sympathetic-adrenomedullary (SAM) system and the hypothalamic–pituitary–adrenocortical (HPA) axis (Kirschbaum et al., 1995; Sgoifo et al., 1996; Gerra et al., 2001; Schommer et al., 2003). In the short term, the HPA axis and the SAM system effectively manage the adaptive response to these stressful events through dynamic mutual interactions. However, as postulated by McEwen in his allostatic theory of stress adaptation and pathology, the same physiologic mediators that maintain homeostasis are also involved in allostatic overload when they are not turned off efficiently after the challenge or not turned on in adequate amounts when needed (McEwen, 1998; Goldstein and McEwen, 2002).
Human and animal data indicate that psychosocial stress can bring about various cardiocirculatory and pathophysiological complications, including atherosclerosis, hypertension, myocardial stunning, acute coronary syndrome, reduced heart rate variability, cardiac arrhythmias and myocardial structural damage (Kaplan and Manuck, 1999; Sgoifo et al., 1999; al’Absi and Arnett, 2000; Knardahl, 2000; Lucini et al., 2002; Costoli et al., 2004; Wittstein et al., 2005; Rozanski et al., 2005, Strike et al., 2006).
There is also evidence suggesting that the amplitude of cardiovascular reactivity to acute stressors can predict the development of preclinical and clinical cardiovascular states (Treiber et al., 2003). The reactivity hypothesis of cardiovascular risk postulates that individuals with exaggerated cardiovascular response to stressors are at higher risk of developing cardiovascular morbidity (Krantz and Manuck, 1984; Burleson et al., 2003). Given that it takes years for such a condition to develop, the tendency towards hyper-responsivity must be stable and reproducible over time (Manuck et al., 1993). Indeed, behaviorally evoked cardiovascular response appears to be a relatively stable individual trait, showing reasonable consistency across time and stressors (Sherwood and Turner, 1995; Sgoifo et al., 2003). For these reasons, it is clinically relevant to investigate individual differences in acute cardiovascular stress responsivity and to try to figure out the role of different modulating variables accounting for such individual variability. In this regard, the HPA axis function, sex steroid levels, and the individual strategy of behavioral coping with psychosocial challenges represent three important modulators.
Clinical and basic science studies underline the role of glucocorticoids in cardiovascular stress responsivity (Litchfield et al., 1998; Sapolsky et al., 2000; Larson et al., 2001; Roy et al., 2001; Schommer et al., 2003). It is generally accepted that appropriate cortisol levels are crucial for catecholamines to exert basic effects on the cardiovascular system, such as vasoconstriction and sinus tachycardia (Dickerson and Kemeny, 2004). Moreover, baseline cortisol levels can be predictive of heart rate reactivity induced by a public speech task (Larson et al., 2001), and individual differences in cardiovascular reactivity appear to predict cortisol changes due to a mental arithmetic challenge (Uchino et al., 1995). Indeed, baseline glucocorticoid levels rather than stress-induced responses are likely to be more essential as modulators of cardiovascular reactivity (Sapolsky et al., 2000).
Besides glucocorticoids, differences in sexual steroid concentrations (due to gender, menstrual cycle phase, menopausal status, and pregnancy) account for different cardiac autonomic and HPA axis stress responses (Kudielka and Kirschbaum, 2005; Kajantie and Phillips, 2006). Earlier studies in women using mild to moderate psychosocial stressors reported similar cardiovascular and HPA axis responses, regardless of the menstrual cycle phase (Abplanalp et al., 1977; Stoney et al., 1990). However, the use of standardized stress protocols has highlighted considerable variations. In particular, the luteal phase (i.e. high estrogen and progestin concentrations) was shown to be characterized by greater adrenocortical response and sensitivity, and buffered cardiovascular responsivity (Tersman et al., 1991; Sita and Miller, 1996; Kirschbaum et al., 1999). As for glucocorticoids, the role of sex hormones in modifying the incidence of cardiovascular disease is largely acknowledged (Kalin and Zumoff, 1990). A substantial body of biological data supports the important role of estrogens in reducing the risk of cardiac and vascular morbidity (Grodstein et al., 1996; Pepine et al., 2006; Bolego et al., 2006; Turgeon et al., 2006). Such protective action appears to be exerted via different mechanisms, involving lipoprotein metabolism, direct effect on the vessel wall, and modulation of sympatho-vagal balance (Farhat et al., 1996; Pare et al., 2002; Saleh and Connell, 2003).
Another important issue about cardiovascular stress reactivity and morbidity concerns the role of individual differences in behavioral response to stressors (Rozanski et al., 1999; Lerner et al., 2005). For instance, when facing stressful tasks, some participants may respond with a proactive coping style, whereas others may adopt a reactive coping strategy (Ursin and Olff, 1993). These different modes of behavioral coping with a stressor may bring about different autonomic/neuroendocrine responses in ways that have important clinical implications (Korte et al., 2005). The ethological approach to the analysis of human behavior represents a powerful tool for highlighting individual differences in behavioral coping and allows to compare physiological parameters with objectively quantified behavioral scores (Troisi, 1999). Via this approach, a previous study by our research group found a close relationship between the degree of autonomic/neuroendocrine arousal and the style of behavioral adaptation to psychosocial stressors (Sgoifo et al., 2003).
The present study performed on young women aims to shed further light on the role of natural fluctuations of estrogen levels (associated with different phases of the menstrual cycle) on cardiac and HPA axis activity, and stress responsivity. The cardiovascular measurements consisted in indirect evaluation of the sympathovagal balance at the sinoatrial node (heart rate and heart rate variability parameters), while the HPA axis function was assessed by determining plasma cortisol and dehydroepiandrosterone (DHEA) concentrations. We also investigated whether individual differences in the style of behavioral coping, quantified by means of a detailed analysis of non-verbal behavior, were differentially associated with HPA axis and cardiac autonomic stress responsivity.
Section snippets
Participants
Data were collected from 36 healthy female university students. Their mean age was 23.4 years (±0.4, SEM), body weight 58.3 kg (±1.4), height 1.66 m (±0.01), and body mass index 21.1 kg/m2 (±0.04). The participants were requested to confirm that: (i) they had had regular menstrual cycles of 26–30 days for the 6 months prior to participation in the study, (ii) they had not used oral contraceptives, (iii) they were not pregnant, (iv) they were not under any kind of chronic pharmacological treatment,
Cardiac autonomic responses
Two-way ANOVA applied to 5-min mean values, revealed a significant effect of the “time” factor for RR (F=8.5, p<0.01) and r-MSSD (F=4.2, p<0.01; Table 1).
The within-group post hoc analysis revealed a clear reduction of RR and r-MSSD values during Test1 as compared to baseline, though statistical significance was reached only for RR (RR—D4: t=3.09, p<0.01; D14: t=2.24, p<0.05; r-MSSD—D4: t=1.93, p=0.07; D14: t=1.57, p=0.08). On the contrary, Test2 did not induce significant RR changes as
Discussion
The present study examined short-term cardiac and adrenocortical responses to a laboratory stressor consisting in two brief, consecutive challenges, namely a stress interview and a mental task. The first objective was to shed additional light on the influence of spontaneous sex steroid fluctuations due to menstrual cycling on autonomic and neuroendocrine stress activations, with particular emphasis on the role of estrogens. For this purpose, we studied young women with regular menstrual cycle
Role of the funding source
The funding source was a grant from the the Italian Ministry for Education, University and Research and from the University of Parma. The study reported in the manuscript was one of the experiments detailed in the grants. The funding bodies played no actual role in the collection analysis or interpretation of the data or in the writing of the report or in the decision to submit the paper for publication.
Conflict of interest
There are no conflicts of interest to report the current manuscript.
Acknowledgments
This study was supported by grants from the Italian Ministry for Education, University and Research and from the University of Parma.
References (78)
- et al.
Adrenocortical responses to psychological stress and risk for hypertension
Biomed. Pharmacother.
(2000) - et al.
Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid receptor mRNA expression in the luteal phase of the menstrual cycle
Neuropsychopharmacology
(1997) - et al.
Vagal modulation and aging
Biol. Psychol.
(2007) - et al.
Animal models and ethological strategies for early drug-testing in humans
Neurosci. Biobehav. Rev.
(1998) - et al.
Neuroendocrine responses to experimentally-induced psychological stress in healthy humans
Psychoneuroendocrinology
(2001) - et al.
Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects—a randomized controlled trial
Psychoneuroendocrinology
(2006) - et al.
The effects of sex and hormonal status on the physiological response to acute psychosocial stress
Psychoneuroendocrinology
(2006) - et al.
Sex hormones and coronary disease: a review of the clinical studies
Steroids
(1990) - et al.
Premenopausal social status and hormone exposure predict postmenopausal atherosclerosis in female monkeys
Obstet. Gynecol.
(2002) - et al.
The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade-offs in health and disease
Neurosci. Biobehav. Rev.
(2005)
Sex differences in HPA axis responses to stress: a review
Biol. Psychol.
Facial expressions of emotion reveal neuroendocrine and cardiovascular responses
Biol. Psych.
Physiological stress reactivity and recovery: conceptual siblings separated at birth?
J. Psychosom. Res.
Menstrual cycle status and adrenocortical reactivity to psychological stress
Psychoneuroendocrinology
Psychological, cardiovascular, and metabolic correlates of individual differences in cortisol stress recovery in young men
Psychoneuroendocrinology
The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology
JACC
Estrogen-induced autonomic effects are mediated by NMDA and GABAA receptors in the parabrachial nucleus
Brain Res.
Individual differences in plasma catecholamine and corticosterone stress responses of wild-type rats: relationship with aggression
Physiol. Behav.
Social stress, autonomic neural activation, and cardiac activity in rats
Neurosci. Biobehav. Rev.
Cardiac autonomic responses to intermittent social conflict in rats
Physiol. Behav.
Cardiac autonomic reactivity and salivary cortisol in men and women exposed to social stressors: relationship with individual ethological profile
Neurosci. Biobehav. Rev.
Estradiol, progesterone and cardiovascular response to stress
Psychoneuroendocrinology
Heart rate variability: a measure of cardiac autonomic tone
Am. Heart J.
Neuroendocrine and cardiovascular correlates of positive affect measured by ecological momentary asessment and by questionnaire
Psychoneuroendocrinology
Ethological research in clinical psychiatry: the study of non-verbal behaviour during interviews
Neurosci. Biobehav. Rev.
Scent-marking and cortisol response in the small-eared bushbaby (Otolemur garnettii)
Physiol. Behav.
Cortisol and growth hormone responses to psychological stress during the menstrual cycle
Psychosom. Med.
Engagement in a non-escape (displacement) behavior elicits a selective and lateralized suppression of frontal cortical dopaminergic utilization in stress
Synapse
The ability of several short-term measures of RR variability to predict mortality after myocardial infarction
Circulation
Selective agonists of estrogen receptor isoforms: new perspectives for cardiovascular disease
Arterioscler. Thromb. Vasc. Biol.
Neuroendocrine and cardiovascular reactivity to stress in mid-aged and older women: long-term temporal consistency of individual differences
Psychophysiology
Disorders of the ovary and female reproductive tract
Effects of chronic psychosocial stress on cardiac autonomic responsiveness and myocardial structure in mice
Am. J. Physiol. Heart. Circ. Physiol.
Endorphines implicated in stereotypies of tethered sows
Experientia
Behavioral, physiological and functional aspects of stereotyped behavior: a review and re-interpretation
J. Anim. Sci.
Stress in domestic animals: a psychoneuroendocrine approach
Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research
Psychol. Bull.
The vascular protective effects of estrogen
FASEB J.
Allostasis, homeostats, and the nature of stress
Stress
Cited by (64)
Signal value of stress behaviour
2022, Evolution and Human BehaviorCitation Excerpt :In humans, these behaviours appear to mainly manifest through self-directed ‘comfort’ behaviours such as self-grooming face-touching, head scratching and through behaviours through the iterative manipulation of objects such as fumbling with jewellery, and chewing on pens (Troisi, 1999). These behaviours may have proximate function to regulate the experience of stress (Mohiyeddini, Bauer, & Semple, 2013), as individuals who produce more stress-associated behaviour seem to recover from a stressful event quicker; measured through lower self-reported stress (Mohiyeddini & Semple, 2013) and through lower heart rate post stressful event (Pico-Alfonso et al., 2007). In non-human primates, there is also strong pharmacological evidence linking these behaviours to stress, and increased rates of self-scratching in monkeys are positively associated with the administration of anxiety-inducing drugs (and negatively associated with anxiety-relieving drugs) (Troisi, 2002).
Cellular and serotonergic correlates of habituated neuroendocrine responses in male and female rats.
2022, Psychoneuroendocrinology