Sex Hormones: Estrogen, Testosterone, and Dehydroepiandrosterone
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As noted previously, women and men often have different stress responses, and this may be partially attributable to the influences of the sex hormones and their interactions with the mediators of allostasis. Excessive stress appears, in general, to inhibit female reproduction and affect premenstrual symptoms. Cortisol exerts inhibiting effects on the female reproductive system by suppressing release of gonadotropin-releasing hormone, luteinizing hormone, estradiol, and progesterone; whereas estradiol normally down-regulates glucocorticoid receptor binding in the brain and alters regulatory feedback control. Androgens, such as testosterone and dehydroepiandrosterone (DHEA), also may inhibit the effects of glucocorticoids. Androgens oppose the catabolic effects of glucocorticoids on bone and the impact of glucocorticoids on lymphoid tissues, inflammatory cytokines, and leukocytes. DHEA
20 UNIT I Pathophysiologic Processes
bend without breaking in the face of environmental or psychological perturbations.”
Because allostasis is a process of attaining and maintaining stability through change that leads to a state of adaptation, the terms adaptation and resilience have been intertwined with allostasis. Resilience is the capacity to “adapt to stress and adversity,” thereby preventing the development of disease and mitigating the effects of allostatic load. It means attaining a positive outcome when encountering adversity. Resilience can be affected by multiple factors, some of which include genetics; epigenetic changes resulting from early life exposure to traumatic events; the availability of social support and coping mechanisms; a sense of optimism and control; prior learning; and lifestyle factors such as physical activity (exercise), diet and nutrition, and adequate sleep. Resilience is influenced by the chemical allostatic mediators that promote adaptation such as cortisol, and some neural proteins such as brain- derived neurotrophic factor (BDNF), which may be necessary for brain plasticity.
Maladaptation, a less frequently used term, refers to ineffective, inadequate, or inappropriate change in response to new or altered circumstances. Coping is another term used and is most often seen as a behavioral adaptive response to a stressor. Coping mechanisms are typically culturally based, and consequently vary with the individual within the parameters of what is acceptable to the given culture. The coping behavior is usually dictated by the specific stressor; thus it fluctuates with the circumstances, but individuals typically embrace a specific repertoire of coping behaviors. These behavioral adaptations allow an individual or a group to withstand successfully the stressful experience or the stress response generated by the experience. A coping strategy can be considered effective or functional if it helps resolve either the situation or the feelings. In some cases, such as exercise, mindfulness meditation, and seeking social support, the coping method can promote health. A coping strategy is considered ineffective or dysfunctional if it does not achieve the desired goal. Coping that achieves unintended goals is considered dysfunctional or maladap- tive. Adaptation may result in the adoption of less-than-desirable coping behaviors, such as excessive eating or alcohol consumption, smoking, or other types of substance abuse and avoidance behaviors. Unfortunately, these dysfunctional coping behaviors can ultimately be damaging to overall health. Smoking and overeating contribute to ath- erosclerosis, the underlying pathophysiology of coronary artery disease and a risk factor for hypertension. Excess weight accumulated through overeating is a contributing factor for type 2 diabetes mellitus and metabolic syndrome. Although coping is customarily interpreted as behavioral adaptation only, the terms coping and adapting often are used interchangeably.
Perception and expectations of the stressor can affect its interpretation, and therefore the behavior evoked by it. Perceptions can be related to uncertainty about the meaning of the stressor. Consider the stressor of undue noise. The “bang” of a car backfiring could also be the sound of a gun being fired. Depending on the environment and circumstances, one or the other etiology would be more expected, dictating different adaptive responses. The term distress describes the experience of perceiv- ing an inability to cope with a physiological or psychological stressor. This distress further activates the release of catecholamines from the adrenal gland medulla and glucocorticoids through the HPA axis, escalating levels of circulating mediators, and may exacerbate existing allostatic load and preexisting pathophysiologic conditions. For instance, the person with asthma who is experiencing an episode of acute shortness of breath is likely to become even more short of breath when discovering an inhaler is not readily available.
Adaptation to a stressor can occur in several ways. Loud noise is a known stressor. Yet people who live close to busy airports often reach