- 1 Stress, Health, And Disease: The Physiology And Pathophysiology Of Stress And The Stress Response
- 2 Eustress And Distress
- 3 Differential Diagnosis
- 4 Conventional Therapies For Hypothalamic-Pituitary-Adrenal Axis Dysfunction
- 5 Botanical Approaches To Stress And HPA Axis Dysregulation
- 6 Stress: Additional Therapies
Stress, Adaptation, The Hypothalamic-Pituitary-Adrenal-Axis (HPA) And Women’s Health
Viewed from the perspective of the evolution of the animal kingdom, sustained psychological stress is a recent invention, mostly limited to humans and other social primates.
— Robert Sapolsky, author, Why Zebras Don’t Get Ulcers
Stress is a fact of life. However, for most of our biological history, stress was a short-term crisis, after which, according to Robert Sapolsky, author of Why Zebras Don’t Get Ulcers, “it’s either over with or you’re over with.” Modern society, with its 24 / 7 work requirements and global Internet access, high level of stimulation and demand, and chronic (daily) repeated stresses, has opened us to a whole new realm of chronic, debilitating diseases. Western medicine is beginning to understand what has long been recognized by traditional medicine systems: that stress, or more traditionally viewed, one’s relationship with and response to the world, has an impact on health.
What we now know scientifically is that the challenge of a small amount of stress, whether from positive or negative stressors (eustress / distress), can actually increase the overall health and performance of the individual organism, but that prolonged or repeated stress leads to wear and tear on the body — allostatic load — part of a deleterious picture leading to numerous health consequences. These may include reproductive disorders, endocrine dys-regulation, insulin resistance (Syndrome X), obesity, chronic fatigue syndrome (CFS), cardiovascular disease, osteoporosis, impaired immunity and autoimmune disorders, cognitive impairment, thyroid disorders, chronic anxiety, postpartum depression, and major depression, to name a few of the big players. It might not surprise readers that women are experiencing these conditions in increasing and significant numbers. Although stress is not the sole cause of these illnesses — as most illnesses have multifactorial etiologies — stress appears to be an underlying factor in many conditions. Unlike exposure to environmental toxins and radiation, or traffic patterns, and other factors over which we have little control, it may be one factor whose effects we have the ability to minimize.
Stress, Health, And Disease: The Physiology And Pathophysiology Of Stress And The Stress Response
The groundwork for the scientific understanding of the physiology of mind-body interactions was first established in the 1930s by the work of Walter Cannon, and followed in the 1940s by the extensive work of Hans Selye, who first formally elaborated the concept of stress and its effects on physiology.s Selye is also credited with introducing the terms corticoids, glucocor-ticoids, and mineralocorticoids, and through his work demonstrated the “triad of stress”: adrenal enlargement, GI ulcers, and thymus gland atrophy, in response to exposure to chronic stressors. George Chrousos summarizes stress and the stress response as follows:
Life exists by maintaining a complex dynamic equilibrium, or homeostasis, that is constantly challenged by intrinsic or extrinsic adverse forces or stressors. Stress is, thus, defined as a state of threatened homeostasis, which is reestablished by a complex repertoire of physiologic and behavioral adaptive responses of the organism. The adaptive responses may be inadequate for the reestablishment of homeostasis or excessive and prolonged; in either case a healthy steady state is not attained, and pathology may ensue.49
Stressors are threats to homeostasis and the adaptive responses are the counteracting forces intended to reestablish it.” Selye termed the adaptive stress response general adaptation syndrome, and demonstrated that it consisted of a consistent set of physiologic responses that included initial response to the stressor followed by an exhaustion phase, and eventually a recovery phase.
More recently the stress response has been renamed allostasis, the ability of the organism to maintain stability, or homeostasis, through change. McEwen elaborates:
The terms, “allostasis” and “allostatic overload,” allow for a more accurate definition of the overused word “stress” and provide a view of how the essential protective and adaptive effects of physiological mediators that maintain homeostasis — the body’s optimal set points for important factors such as blood pressure, fluid balance, pH, glucose levels, oxygen levels, temperature, etc. — are also involved in the cumulative effects of daily life when they are mismanaged or overused. When mediators of allostasis, like cortisol and adrenaline, are released in response to stressors or to lifestyle factors such as diet, sleep, and exercise, they promote adaptation and are generally beneficial. However, when these mediators are not turned off when the stress is over, or when they are not turned on adequately during stress, or when they are overused by many stressors, there are cumulative changes that lead to a wear-and-tear, called “allostatic load or overload,” on the body and brain. The concept of allostasis refers to the network of interacting mediators by which stability, that is, homeostasis, is achieved through change. There are primary mediators of allostasis, such as, but not confined to, hormones of the hypothalamic-pituitary-adrenal (HPA) axis, catechola-mines, and cytokines. These mediators interact with each other to create a network of reciprocal effects.
Our bodies possess complex and elegant mechanisms for responding to and recovering from acute exposure to stressors. The neuroendocrine system has evolved two primary pathways responsible for responding and adapting to potentially harmful or life-threatening encounters: the sympathoadrenal system (SAS) and hypothalamic-pituitary-adrenal axis (HPA). Both mediate a two-way brain-body communication that sets in motion a series of hormonal and neuroendocrine responses that “switch on” and “switch off” what has been commonly referred to as the “fight or flight” response.,s In response to the alert system being switched on, the body’s resources are mobilized for protective action: The heart rate increases and blood is diverted from digestion (who needs to digest when being chased by the proverbial saber tooth tiger?) into the periphery, especially the legs (yup, you want to be able to run away from the tiger!), the respiratory rate increases, blood pressure increases and urinary output decreases, the pupils dilate to increase sight, and other senses such as hearing and smell become keener, the mind becomes sharp and alert and vigilance is enhanced, appetite decreases, immunity is suppressed, and large amounts of sugar are delivered to the bloodstream via lypolysis and gluconeogenesis to fuel the energy needed for a massive response. Growth, reproduction, and sexual response are inhibited — resources are instead diverted to immediate life-saving needs, rather than toward what Sapolsky refers to as optimistic activities. In the recovery phase, interestingly, the body responds to the need for repair by increasing appetite and storing fat (primarily in the abdomen).
Hormonal and neuroendocrine mediators and messengers from the sympathetic nervous system and hypothalamic-pituitary-adrenal axis orchestrate all of these responses. At the first sign of threat, or even a perceived threat, the sympathetic nervous system goes into action. Epinephrine (adrenaline) and norepinephrine (noradrenalin) are released from the nerve endings of the adrenal glands and the rest of the body, respectively, and begin to stimulate the body to further reaction in a matter of seconds. The hypothalamus releases a substance called corticotrophin-releasing hormone (CRH), which triggers the release of ACTH (corticotrophin), which within a few minutes reaches the adrenal glands, where it causes the release of glucocorti-coids (cortisol, corticosteroids). The pancreas releases glu-cagons, which with the glucocorticoids increase the levels of circulating glucose. Glucocorticoids do this via the promotion of protein and lipid degradation from muscle, skin, and fat. Energy is mobilized at the expense of storage. Other hormones are released as well. Prolactin is secreted by the pituitary, and plays a role in the suppression of reproduction during stress. Endorphins and enke-phalins are released, blunting pain perception, while vasopressin (antidiuretic hormone) is released from the pituitary, and maintains blood pressure, forestalling for example, hypovolemic shock in the event of massive blood loss. Prostaglandins, PAF, and NO are all stimulated. The allostatic response also inhibits the release of numerous hormones, for example, estrogen, progesterone, and testosterone, as well as growth hormone and insulin.
Prolonged and repeated exposure to aversive events — as well as anticipation of aversive events (e.g., worry and anxiety about future or impending events such as an interview, an exam, paying the bills) — may lead to a sustained activation and dysregulation of the hypothalamic-pituitary-adrenal axis. In time, allostatic states place wear and tear on the regulatory systems of the brain and body, which can lead to hypothalamic-pituitary-adrenal hyperfunctioning or hypofunctioning (respectively, the inability to turn off, or turn on the adaptive response) maladaptive responses thought to be causally linked to a number of disorders via glucocorticoid and other effects on the cardiovascular system, mobilization of bone stores of calcium, effects on weight and fat distribution, hormonal effects on the reproductive system, thyroid effects, and so forth.”’
Women are more likely to experience menstrual irregularities, anovulation, infertility, osteoporosis, chronic fatigue, autoimmunity, and cardiovascular disease, Syndrome X, and diabetes, for example. Further, there is significant evidence that a history of childhood sexual or psychological abuse predisposes to hypothalamic-pituitary-adrenal dysfunction later in life. Excessive exercise (overtraining) also can lead to hypothalamic-pituitary-adrenal dysfunction with increased fatigue and decreased immune response. Irregular and inadequate food intake, regular hypoglycemic episodes, and yo-yo dieting also cause excessive stress and cause blood sugar imbalances that can lead to allostatic overload and eventually hypothalamic-pituitary-adrenal dysregulation.
The medical profession does not define a category of illnesses that encompasses the effects of allostatic load. Prevention and treatment of stress and its effects on the hypothalamic-pituitary-adrenal axis are not considered a part of preventative care or treatment for the numerous and serious stress-related diseases mentioned earlier, with limited exception. Adrenal disease is recognized only in its severest forms: Addison’s disease and Shy-Drager syndrome. Yet the symptoms of hypothalamic-pituitary-adrenal axis dysregulation are rampant in modern society. Aside from overt dysfunction and disease [reproductive disorders and endocrine dysregulation, insulin resistance (syndrome X) and obesity, chronic fatigue syndrome (CFS), cardiovascular disease, osteoporosis, impaired immunity and autoimmune disorders, thyroid disorders, cognitive impairment, chronic anxiety, and major depression], Americans are plagued by fatigue and exhaustion, insomnia, emotional frustration, digestive problems, weight problems, menstrual problems, infertility, menopausal problems, headaches, susceptibility to colds, musculoskeletal tension, allergies and asthma, atopic conditions, and numerous other problems that can be related to stress and chronic hypothalamic-pituitary-adrenal hyperfunctioning or hypofunctioing. The need to address chronic stress as part of the prevention and treatment of chronic illness is more than a lip service to a holistic approach — it is a significant part of a comprehensive medical and public health approach to reducing chronic health problems affecting all populations in the United States. It is also an integral aspect of herbal medicine care, as discussed in the following.
Eustress And Distress
Interestingly, pleasant and pleasurable activities (sex, numerous mind-altering and energy-altering substances that are commonly used and abused, heavy exercise) also trigger the stress response. The primary factors distinguishing distress from eustress appear to be the quality and intensity of the stressor, termination of the stress response after a particular stressor has ceased, and the return of homeostasis. Genetic predisposition, life history, and age also seem to play significant roles in the perception of stress and in the stress response.
HPA dysfunction must be distinguished from specific chronic and acute diseases, as well as from frank adrenal disease. Patients complaining of chronic, recurrent symptoms should have serious underlying illness ruled out. hypothalamic-pituitary-adrenal dysfunction then becomes a diagnosis based on exclusion of other possible causes.
Conventional Therapies For Hypothalamic-Pituitary-Adrenal Axis Dysfunction
Although Selye’s work was accepted as logical and well supported, and was validated by numerous subsequent researchers, conventional medicine does not recognize generalized hypothalamic-pituitary-adrenal dysfunction as a discrete entity, much less propose methods for prevention and treatment. Patients presenting with weakness, fatigue, insomnia, anxiety, susceptibility to colds, stress symptoms and stress intolerance are typically prescribed antidepres-sants and anxiolytics. If hypertension and heart palpitations are most prominent, beta-blockers or other cardiovascular medications may be prescribed. If low adrenal function has affected progesterone or reproductive function, hormone replacement is typically offered. If dysglycemia and episodic blood sugar difficulties are the presenting symptoms, the case is often misunderstood. Vital signs and routine blood work, including blood glucose, may often be normal, and the individual is typically told all is fine, or perhaps offered psychiatric medications.