Stress: Additional Therapies


Dehydroepiandrosterone and its active metabolite, dehydroepiandrosterone sulfate, are endogenous hormones synthesized and excreted primarily by the adrenal cortex in response to ACTH. In women, the synthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate occurs almost exclusively in the adrenal cortex. Dehydroepiandrosterone is classified as an androgen, and may be converted into other hormones, including estrogen and testosterone. Dehydroepiandrosterone and dehydroepiandrosterone sulfate serve as the precursors of approximately 75% of active estrogens in premenopausal women, and 100% of active estrogens after menopause. The levels of dehydroepiandrosterone in the blood are typically 10 times those of cortisol.

Dehydroepiandrosterone is active in the CNS, and is taken up by the amygdala, hippocampus, thalamus, midbrain, and frontal cortex. Dehydroepiandrosterone and dehydroepiandrosterone sulfate also appear to have neurotrophic effects, increasing the number of neurofila-ment-positive neurons and regulating the motility and growth of corticothalamic projections in cultured mouse embryo brain cells. Dehydroepiandrosterone and dehydroepiandrosterone sulfate output is maximal between the ages of 20 and 30 years and then declines with age at a rate of approximately 2% per year, leaving a residual of 10% to 20% of the peak production by the eighth or ninth decade of life. The exact mechanism of action and clinical role of dehydroepiandrosterone and dehydroepiandrosterone sulfate remain unclear. Epidemiologic data indicate an inverse relationship between serum dehydroepiandrosterone and dehydroepiandrosterone sulfate levels and the frequency of cancer, cardiovascular disease (in men only), Alzheimer’s disease and other age-related disorders, immune function, and progression of HIV infection.

Beneficial effects of dehydroepiandrosterone, based on animal studies, include improved immune function and memory and prevention of atherosclerosis, cancer, diabetes, and obesity. Clinically validated uses of dehydroepiandrosterone include replacement therapy in patients with low serum dehydroepiandrosterone levels secondary to chronic disease, adrenal exhaustion, or corticosteroid therapy; treating systemic lupus erythematosus (SLE), improving bone density in post-menopausal women; improving symptoms of severe depression; improving depressed mood and fatigue in patients with HIV infection; and increasing the rate of reepithelialization in patients undergoing autolo-gous skin grafting for burns; however, such uses remain controversial. Supporting clinical studies also suggest possible benefit in enhancing immune response and sense of well-being in older adults, and a reduction in some cardiovascular risk factors. Other uses for dehydroepiandrosterone, for example, for retarding the aging process, improving cognition, promoting weight loss, increasing lean muscle mass, and slowing the progression of Parkinson’s disease and Alzheimer’s disease are clinically unsubstantiated.

Dehydroepiandrosterone supplementation has been found to elevate serum testosterone, estrone, and estriol levels in post-menopausal women. Dehydroepiandrosterone may lead to an increase in progesterone production indirectly, because both dehydroepiandrosterone and progesterone require pregnenolone as a precursor. If the body does not have to manufacture dehydroepiandrosterone, more pregnenolone may be shunted to progesterone synthesis. Physiologic replacement dosages of oral dehydroepiandrosterone in healthy women over 40 range from 5 to 30 mg / day, and are usually given once in the morning. This is generally adequate to raise serum dehydroepiandrosterone sulfate to the levels found in adults 20 to 30 years of age and impart the documented benefits of heightened sense of well-being and increased bone mineral density in postmenopausal women. Higher doses may be necessary for increasing suppressed dehydroepiandrosterone and dehydroepiandrosterone sulfate levels secondary to chronic disease, adrenal exhaustion, and corticosteroid therapy. Pharmacologic dosages of 200 mg / day have been successfully used in patients with SLE. Dosages of 200 to 500 mg / day have been used in HIV-positive patients with depressed mood and fatigue. With physiologic and supraphysiologic doses, the most common side effects include acne and mild hirsutism. Rakel suggests that dosing not exceed 50 mg / day of an oral dose regimen in non-adrenal deficient patients. As OTC sources of dehydroepiandrosterone are not standardized, inconsistent dosing with insufficient daily dosing may be a problem.

The long-term effects of significantly raised androgen levels in women using dehydroepiandrosterone are unknown. A case control study of postmenopausal women not taking dehydroepiandrosterone or hormone replacement therapy whose levels of endogenous dehydroepiandrosterone sulfate were in the highest quartile had a significantly higher risk of breast cancer than women whose levels of endogenous dehydroepiandrosterone sulfate were in the lowest quartile. The effects of long-term physiologic or supraphysiologic doses of dehydroepiandrosterone on suppression of adrenal cortex are unknown; however, there does not appear to be feedback inhibition of dehydroepiandrosterone or dehydroepiandrosterone sulfate secretion by the hypothalamic-pituitary-adrenal axis. Baseline dehydroepiandrosterone sulfate should be checked prior to initiating therapy and the serum dehydroepiandrosterone sulfate level should be checked at least annually to ensure that it is in the normal range. Dehydroepiandrosterone can affect (raising some, lowering others) serum levels of: calcium channel blockers, met-formin, corticosteroids, insulin, and triazolam. Diet and exercise also can affect dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. Dehydroepiandrosterone supplementation is contraindicated in patients with a history (personal or family) of sex hormone-responsive cancers. Dehydroepiandrosterone supplementation should be avoided during pregnancy and lactation.

Lifestyle and Reducing the Effects of Stress

Stress is an unavoidable fact of life. Its effects, however, can be mitigated. The effects of lifestyle on preventing and reducing stress, and consequently stress-related illness, cannot be overstated. The following are simple suggestions for managing stress:

• Avoid emotional eating (overeating and undereating). Teach patients to eat healthy foods, in appropriate amounts for their body and lifestyle, when hungry. This will not only keep the body healthy, but will also lead to weight stabilization. For many women, being overweight is both a result of stress and a cause of stress, leading to a vicious cycle.

• Encourage dietary changes that enrich nutrition and reduce empty calories.

• Take a complex multivitamin and mineral supplement to ensure adequate intake of trace nutrients.

• Drink enough fluids throughout the day.

• Get enough sleep and correct sleep. Sleeping adequate amounts is critical to keeping the neuroendocrine system healthy, reducing stress, and caring well for the body. However, sleeping at optimal hours for the body’s hormonal and neurotransmitter systems is also important to health. Cortisol and melatonin, for example, both intrinsic to maintaining proper stress response, have secretory rhythms that are optimized by following diurnal sleep patterns, ideally by going to sleep by 11 pm and rising early in the morning. Although patients with jobs that require night work or women with young children might not be able to achieve this rhythm, lack of this rhythm may be a clue to hypothalamic-pituitary-adrenal access disruption and related illnesses such patients are experiencing.

• Get moderate exercise.

• Engage in relaxation techniques, for example, yoga, tai chi, meditation, art “therapy,” journaling, and so forth.

• Avoid or minimize caffeine intake.

• Address work life, relationship, or environmental stres-sors through making changes, getting counseling, or other means that reduce exposure to life stressors and environmental hazards. Provide patient referral to marriage and family counselors, environmental groups, and so forth, as appropriate.

• Social support is one of the most important factors in stress response and life expectancy. Individuals living in isolation respond more poorly to stress and illness, recover more slowly, and have a lower life expectancy than individuals with an established social network and social support.