Dehydroepiandrosterone in adrenal insufficiency and ageing.
ABSTRACT The physiological role of dehydroepiandrosterone remains unclear, and there is continuing controversy on whether dehydroepiandrosterone treatment benefits adrenal-deficient and elderly people with an age-related decline in dehydroepiandrosterone. The objective of this study is to critically review published results and determine whether there is a valid case for dehydroepiandrosterone treatment with advancing age and hypoadrenalism.
Oral dehydroepiandrosterone therapy in both elderly and hypoadrenal subjects achieves dehydroepiandrosterone levels comparable to young subjects. Long-term dehydroepiandrosterone replacement in elderly people demonstrated no improvement in body composition, physical performance or any metabolic parameters; however, a modest but inconsistent improvement in bone mineral density occurred at certain sites. Dehydroepiandrosterone replacement in hypoadrenalism modestly improved insulin sensitivity and altered the lipid profile, but it remains uncertain whether these changes improve any patient-important outcomes. Dehydroepiandrosterone replacement in adrenal deficiency inconsistently improves some aspects of mental health.
Dehydroepiandrosterone replacement increases bone mineral density in elderly subjects; however, the effect is relatively small compared with established therapies for osteoporosis. No additional benefits have been identified for long-term dehydroepiandrosterone replacement, when used in the elderly to prevent or delay ageing. Dehydroepiandrosterone replacement may improve some metabolic variables and measures of psychological well-being in adrenal deficiency, but these benefits are not consistently sustained in long-term therapy. Long-term studies are needed to confirm sustained benefits in adrenal deficiency and establish long-term safety.
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ABSTRACT: The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging. However, data on the association between DHEA and mortality are conflicting. We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men. We used gas/liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based MrOS Sweden study (2644 men, aged 69-81 yr). Mortality data were obtained from central registers and analyzed using Cox proportional hazards regressions. All-cause and CVD mortality by serum DHEA(-S) levels. Results: During a mean 4.5-yr follow-up, 328 deaths occurred. Low levels of DHEA-S (quartile 1 vs. quartiles 2-4), predicted death from all causes [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.21-1.96; adjusted for traditional cardiovascular risk factors], from CVD (n = 123 deaths; HR 1.61, 95% CI 1.10-2.37) and ischemic heart disease (n = 73; HR 1.67, 95% CI 1.02-2.74) but not cancer. Analyses with DHEA gave similar results. The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger (age adjusted HR for CVD death 2.64, 95% CI 1.37-5.09) than older men (HR 1.30, 95% CI 0.83-2.04). Low serum levels of DHEA(-S) predict death from all causes, CVD, and ischemic heart disease in older men.The Journal of clinical endocrinology and metabolism 09/2010; 95(9):4406-14. · 6.50 Impact Factor
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ABSTRACT: In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is widespread interest in complementary and alternative medicine (CAM) therapies in the treatment of major depressive disorder (MDD). The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. This section on "Complementary and Alternative Medicine Treatments" is one of 5 guideline articles. There is Level 1 evidence to support light therapy in seasonal MDD and St. John's wort in mild to moderate MDD. There is also some evidence for the use of exercise, yoga and sleep deprivation, as well as for omega-3 fatty acids and SAM-e . Support for other natural health products and therapies is still limited. The evidence base remains limited and studies often have methodological problems, including small samples, variability in dose, short duration of treatment, unknown quality of the agent and limited long-term data. Safety data are also sparse with little information about drug interactions. Some CAM treatments have evidence of benefit in MDD. However, problems with standardization and safety concerns may limit their applicability in clinical practice.Journal of affective disorders 09/2009; 117 Suppl 1:S54-64. · 3.76 Impact Factor
Article: Adrenal insufficiency.[show abstract] [hide abstract]
ABSTRACT: Adrenal insufficiency is the clinical manifestation of deficient production or action of glucocorticoids, with or without deficiency also in mineralocorticoids and adrenal androgens. It is a life-threatening disorder that can result from primary adrenal failure or secondary adrenal disease due to impairment of the hypothalamic-pituitary axis. Prompt diagnosis and management are essential. The clinical manifestations of primary adrenal insufficiency result from deficiency of all adrenocortical hormones, but they can also include signs of other concurrent autoimmune conditions. In secondary or tertiary adrenal insufficiency, the clinical picture results from glucocorticoid deficiency only, but manifestations of the primary pathological disorder can also be present. The diagnostic investigation, although well established, can be challenging, especially in patients with secondary or tertiary adrenal insufficiency. We summarise knowledge at this time on the epidemiology, causal mechanisms, pathophysiology, clinical manifestations, diagnosis, and management of this disorder.The Lancet 02/2014; · 39.06 Impact Factor