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      Adrenopause

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          Abstract

          Dehydroepiandrosterone(DHEA) and DHEA-S are steroids that are abundantly produced by the adrenal gland. Plasma concentrations of DHEA and DHEA-S increase during adrenarche but decrease steadily after puberty. Although DHEA and DHEA-S have few intrinsic androgenic actions, they have recently attracted widespread attention due to their beneficial anti-aging effects. We clarified the beneficial effects of DHEA as an anti-aging steroid with regard to its stimulation of the immune system and its anti-diabetes, anti-atherosclerosis, anti-dementia (neurosteroid), anti-obesity and anti-osteoporosis effects. There are two possible biochemical and molecular mechanisms: direct action via the DHEA receptor on the target gene; and indirect action. We identified a high affinity of DHEA binding in human T-lymphocytes by searching for the target genes that are induced in activated T-lymphocytes in the presence of DHEA, determined the gene sequence and named DHEA-induced dual p38-specific phosphatase (DDSP). DDSP transgenic mice have been created to identify the anti-aging effects of DDSP. The conversion of DHEA to estrone by cytochrome P450 aromatase in primary cultured human osteoblasts was clarified. We are currently undertaking an open trial of DHEA replacement therapy.

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          Most cited references 11

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          Biomarkers of caloric restriction may predict longevity in humans.

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            Dehydroepiandrosterone replacement in women with adrenal insufficiency.

            The physiologic role of dehydroepiandrosterone in humans is still unclear. Adrenal insufficiency leads to a deficiency of dehydroepiandrosterone; we therefore, investigated the effects of dehydroepiandrosterone replacement, in patients with adrenal insufficiency. In a double-blind study, 24 women with adrenal insufficiency received in random order 50 mg of dehydroepiandrosterone orally each morning for four months and placebo daily for four months, with a one-month washout period. We measured serum steroid hormones, insulin-like growth factor I, lipids, and sex hormone-binding globulin, and we evaluated well-being and sexuality with the use of validated psychological questionnaires and visual-analogue scales, respectively. The women were assessed before treatment, after one and four months of treatment with dehydroepiandrosterone, after one and four months of placebo, and one month after the end of the second treatment period. Treatment with dehydroepiandrosterone raised the initially low serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone into the normal range; serum concentrations of sex hormone-binding globulin, total cholesterol, and high-density lipoprotein cholesterol decreased significantly. Dehydroepiandrosterone significantly improved overall well-being as well as scores for depression and anxiety. For the global severity index, the mean (+/-SD) change from base line was -0.18+/-0.29 after four months of dehydroepiandrosterone therapy, as compared with 0.03+/-0.29 after four months of placebo (P=0.02). As compared with placebo, dehydroepiandrosterone significantly increased the frequency of sexual thoughts (P=0.006), sexual interest (P=0.002), and satisfaction with both mental and physical aspects of sexuality (P=0.009 and P=0.02, respectively). Dehydroepiandrosterone improves well-being and sexuality in women with adrenal insufficiency.
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              Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age [published erratum appears in J Clin Endocrinol Metab 1995 Sep;80(9):2799]

               A Morales (1994)
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-7833-2
                978-3-318-01154-8
                1663-2818
                1663-2826
                2004
                October 2004
                17 November 2004
                : 62
                : Suppl 3
                : 110-114
                Affiliations
                Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
                Article
                80509 Horm Res 2004;62(suppl 3):110–114
                10.1159/000080509
                15539809
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 15, Pages: 5
                Categories
                Endocrinology of Ageing

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