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: Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin. The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers. This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.Molecular and Cellular Endocrinology 03/2013; · 4.04 Impact Factor
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ABSTRACT: BACKGROUND: Depressed and anxious patients often combine complementary and alternative medicine (CAM) therapies with conventional pharmacotherapy to self-treat symptoms. The benefits and risks of such combination strategies have not been fully evaluated. This paper evaluates the risk-benefit profile of CAM augmentation to antidepressants in affective conditions. METHODS: PubMed was searched for all available clinical reports published in English up to December 2012. Data were evaluated based on graded levels of evidence for efficacy and safety. RESULTS: Generally, the evidence base is significantly larger for depression than for anxiety disorder. In unipolar depression, there is Level 2 evidence for adjunctive sleep deprivation (SD) and Free and Easy Wanderer Plus (FEWP), and Level 3 for exercise, yoga, light therapy (LT), omega-3 fatty acids, S-adenosylmethionine and tryptophan. In bipolar depression, there is Level 1 evidence for adjunctive omega-3s, Level 2 for SD, and Level 3 for LT and FEWP. In anxiety conditions, exercise augmentation has Level 3 support in generalized anxiety disorder and panic disorder. Though mostly well-tolerated, these therapies can only be recommended as third-line interventions due to the quality of available evidence. LIMITATIONS: Overall, the literature is limited. Studies often had methodological weaknesses, with little information on long-term use and on potential drug-CAM interactions. Many CAM studies were not published in English. CONCLUSIONS: While several CAM therapies show some evidence of benefit as augmentation in depressive disorders, such evidence is largely lacking in anxiety disorders. The general dearth of adequate safety and tolerability data encourages caution in clinical use.Journal of affective disorders 06/2013; · 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