It has been postulated that dehydroepiandrosterone (DHEA) and its sulfate ester, dehydroepiandrosterone sulfate (DHEAS), the major secretory products of the human adrenal gland, may be discriminators of life expectancy and aging. We examined the relation of base-line circulating DHEAS levels to subsequent 12-year mortality from any cause, from cardiovascular disease, and from ischemic heart disease in a population-based cohort of 242 men aged 50 to 79 years at the start of the study. Mean DHEAS levels decreased with age and were also significantly lower in men with a history of heart disease than in those without such a history. In men with no history of heart disease at base line, the age-adjusted relative risk associated with a DHEAS level below 140 micrograms per deciliter was 1.5 (P not significant) for death from any causes, 3.3 (P less than 0.05) for death from cardiovascular disease, and 3.2 (P less than 0.05) for death from ischemic heart disease. In multivariate analyses, an increase in DHEAS level of 100 micrograms per deciliter was associated with a 36 percent reduction in mortality from any causes (P less than 0.05) and a 48 percent reduction in mortality from cardiovascular disease (P less than 0.05), after adjustment for age, systolic blood pressure, serum cholesterol level, obesity, fasting plasma glucose level, cigarette smoking status, and personal history of heart disease. Our conclusions are limited by the single determination of DHEAS levels, but the data suggest that the DHEAS concentration is independently and inversely related to death from any cause and death from cardiovascular disease in men over age 50.
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[Abstract][Full Text]
Hougaku, H., Fleg, J. L., Najjar, S. S., Lakatta, E. G., Harman, S. M., Blackman, M. R., Metter, E. J.
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290: E234-E242
[Abstract][Full Text]
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[Abstract][Full Text]
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26: 833-876
[Abstract][Full Text]
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[Abstract][Full Text]
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110: 1787-1793
[Abstract][Full Text]
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(2004). Dehydroepiandrosterone-Sulfate Inhibits Nuclear Factor-{kappa}B-Dependent Transcription in Hepatocytes, Possibly through Antioxidant Effect. J. Clin. Endocrinol. Metab.
89: 3449-3454
[Abstract][Full Text]
Riechman, S. E., Fabian, T. J., Kroboth, P. D., Ferrell, R. E.
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17: 300-306
[Abstract][Full Text]
Molinari, C., Battaglia, A., Grossini, E., Mary, D. A. S. G., Vassanelli, C., Vacca, G.
(2004). The effect of dehydroepiandrosterone on regional blood flow in prepubertal anaesthetized pigs. J. Physiol.
557: 307-319
[Abstract][Full Text]
Ng, M. K. C., Nakhla, S., Baoutina, A., Jessup, W., Handelsman, D. J., Celermajer, D. S.
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[Abstract][Full Text]
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(2003). Endogenous Sex Hormones and Cardiovascular Disease in Men. J. Clin. Endocrinol. Metab.
88: 5076-5086
[Abstract][Full Text]
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[Abstract][Full Text]
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[Abstract][Full Text]
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(2003). Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men. J. Clin. Endocrinol. Metab.
88: 3190-3195
[Abstract][Full Text]
Liu, P. Y., Death, A. K., Handelsman, D. J.
(2003). Androgens and Cardiovascular Disease. Endocr. Rev.
24: 313-340
[Abstract][Full Text]
van Dam, E. W.C.M., Dekker, J. M., Lentjes, E. G.W.M., Romijn, F. P.T.H.M., Smulders, Y. M., Post, W. J., Romijn, J. A., Krans, H. M. J.
(2003). Steroids in Adult Men With Type 1 Diabetes: A tendency to hypogonadism. Diabetes Care
26: 1812-1818
[Abstract][Full Text]
Wu, F. C. W., von Eckardstein, A.
(2003). Androgens and Coronary Artery Disease. Endocr. Rev.
24: 183-217
[Abstract][Full Text]
Liu, D., Dillon, J. S.
(2002). Dehydroepiandrosterone Activates Endothelial Cell Nitric-oxide Synthase by a Specific Plasma Membrane Receptor Coupled to Galpha i2,3. J. Biol. Chem.
277: 21379-21388
[Abstract][Full Text]
Nestler, J. E., Whitfield, J. B., Williams, T. Y., Zhu, G., Condon, J., Kirk, K. M., Heath, A. C., Montgomery, G. W., Martin, N. G.
(2002). Genetics of Serum Dehydroepiandrosterone Sulfate and Its Relationship to Insulin in a Population-Based Cohort of Twin Subjects. J. Clin. Endocrinol. Metab.
87: 682-686
[Abstract][Full Text]
Trivedi, D. P., Khaw, K. T.
(2001). Dehydroepiandrosterone Sulfate and Mortality in Elderly Men and Women. J. Clin. Endocrinol. Metab.
86: 4171-4177
[Abstract][Full Text]
Tagliaferro, A. R., Ronan, A. M.
(2001). Physiological levels and action of dehydroepiandrosterone in Yucatan miniature swine. Am. J. Physiol. Regul. Integr. Comp. Physiol.
281: R1-R9
[Abstract][Full Text]
Mazat, L., Lafont, S., Berr, C., Debuire, B., Tessier, J.-F., Dartigues, J.-F., Baulieu, E.-E.
(2001). Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: Relationship to gender, subjective health, smoking habits, and 10-year mortality. Proc. Natl. Acad. Sci. USA
10.1073/pnas.121177998v1
[Abstract][Full Text]
Vermeulen, A.
(2001). Androgen Replacement Therapy in the Aging Male--A Critical Evaluation. J. Clin. Endocrinol. Metab.
86: 2380-2390
[Full Text]
Dessein, P. H., Stanwix, A. E., Moomal, Z., Symmons, D., Harrison, B.
(2001). Rheumatoid arthritis and cardiovascular disease may share similar risk factors. Rheumatology (Oxford)
40: 703-704
[Full Text]
Feldman, H. A., Johannes, C. B., Araujo, A. B., Mohr, B. A., Longcope, C., McKinlay, J. B.
(2001). Low Dehydroepiandrosterone and Ischemic Heart Disease in Middle-aged Men: Prospective Results from the Massachusetts Male Aging Study. Am J Epidemiol
153: 79-89
[Abstract][Full Text]
Hunt, P. J., Gurnell, E. M., Huppert, F. A., Richards, C., Prevost, A. T., Wass, J. A. H., Herbert, J., Chatterjee, V. K. K.
(2000). Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison's Disease in a Randomized, Double Blind Trial. J. Clin. Endocrinol. Metab.
85: 4650-4656
[Abstract][Full Text]
Khalil, A., Fortin, J.-P., LeHoux, J.-G., Fülöp, T.
(2000). Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation. J. Lipid Res.
41: 1552-1561
[Abstract][Full Text]
Rosano, G.M.C.
(2000). Androgens and coronary artery disease. A sex-specific effect of sex hormones?. Eur Heart J
21: 868-871
Moriyama, Y., Yasue, H., Yoshimura, M., Mizuno, Y., Nishiyama, K., Tsunoda, R., Kawano, H., Kugiyama, K., Ogawa, H., Saito, Y., Nakao, K.
(2000). The Plasma Levels of Dehydroepiandrosterone Sulfate Are Decreased in Patients with Chronic Heart Failure in Proportion to the Severity. J. Clin. Endocrinol. Metab.
85: 1834-1840
[Abstract][Full Text]
Kiechl, S., Willeit, J., Bonora, E., Schwarz, S., Xu, Q.
(2000). No Association Between Dehydroepiandrosterone Sulfate and Development of Atherosclerosis in a Prospective Population Study (Bruneck Study). Arterioscler. Thromb. Vasc. Bio.
20: 1094-1100
[Abstract][Full Text]
Tagawa, N., Tamanaka, J., Fujinami, A., Kobayashi, Y., Takano, T., Fukata, S., Kuma, K., Tada, H., Amino, N.
(2000). Serum Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate, and Pregnenolone Sulfate Concentrations in Patients with Hyperthyroidism and Hypothyroidism. Clin. Chem.
46: 523-528
[Abstract][Full Text]
Hayward, C. S., Kelly, R. P., Collins, P.
(2000). The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc Res
46: 28-49
[Full Text]
Deuster, P. A., Petrides, J. S., Singh, A., Chrousos, G. P., Poth, M.
(2000). Endocrine Response to High-Intensity Exercise: Dose-Dependent Effects of Dexamethasone. J. Clin. Endocrinol. Metab.
85: 1066-1073
[Abstract][Full Text]
Ciolino, H. P., Yeh, G. C.
(1999). The Steroid Hormone Dehydroepiandrosterone Inhibits CYP1A1 Expression in Vitro By a Post-transcriptional Mechanism. J. Biol. Chem.
274: 35186-35190
[Abstract][Full Text]
Solerte, S. B., Fioravanti, M., Vignati, G., Giustina, A., Cravello, L., Ferrari, E.
(1999). Dehydroepiandrosterone Sulfate Enhances Natural Killer Cell Cytotoxicity in Humans Via Locally Generated Immunoreactive Insulin-Like Growth Factor I. J. Clin. Endocrinol. Metab.
84: 3260-3267
[Abstract][Full Text]
Arlt, W., Haas, J., Callies, F., Reincke, M., Hübler, D., Oettel, M., Ernst, M., Schulte, H. M., Allolio, B.
(1999). Biotransformation of Oral Dehydroepiandrosterone in Elderly Men: Significant Increase in Circulating Estrogens. J. Clin. Endocrinol. Metab.
84: 2170-2176
[Abstract][Full Text]
McCrohon, J. A., Jessup, W., Handelsman, D. J., Celermajer, D. S.
(1999). Androgen Exposure Increases Human Monocyte Adhesion to Vascular Endothelium and Endothelial Cell Expression of Vascular Cell Adhesion Molecule-1. Circulation
99: 2317-2322
[Abstract][Full Text]
Alexandersen, P., Haarbo, J., Byrjalsen, I., Lawaetz, H., Christiansen, C.
(1999). Natural Androgens Inhibit Male Atherosclerosis : A Study in Castrated, Cholesterol-Fed Rabbits. Circ. Res.
84: 813-819
[Abstract][Full Text]
Pugh, T. D., Oberley, T. D., Weindruch, R.
(1999). Dietary Intervention at Middle Age: Caloric Restriction but not Dehydroepiandrosterone Sulfate Increases Lifespan and Lifetime Cancer Incidence in Mice. Cancer Res.
59: 1642-1648
[Abstract][Full Text]
Ishizuka, T., Kajita, K., Miura, A., Ishizawa, M., Kanoh, Y., Itaya, S., Kimura, M., Muto, N., Mune, T., Morita, H., Yasuda, K.
(1999). DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase. Am. J. Physiol. Endocrinol. Metab.
276: E196-E204
[Abstract][Full Text]
Morrison, M. F., Katz, I. R., Parmelee, P., Boyce, A. A., TenHave, T.
(1998). Dehydroepiandrosterone Sulfate (DHEA-S) and Psychiatric and Laboratory Measures of Frailty in a Residential Care Population. AJGP
6: 277-284
[Abstract][Full Text]
Jansson, J-H, Nilsson, T K, Johnson, O
(1998). von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction. Heart
80: 334-337
[Abstract][Full Text]
Straub, R. H., Konecna, L., Hrach, S., Rothe, G., Kreutz, M., Schölmerich, J., Falk, W., Lang, B.
(1998). Serum Dehydroepiandrosterone (DHEA) and DHEA Sulfate Are Negatively Correlated with Serum Interleukin-6 (IL-6), and DHEA Inhibits IL-6 Secretion from Mononuclear Cells in Man in Vitro: Possible Link between Endocrinosenescence and Immunosenescence. J. Clin. Endocrinol. Metab.
83: 2012-2017
[Abstract][Full Text]
Labrie, F., Diamond, P., Cusan, L., Gomez, J.-L., Belanger, A., Candas, B.
(1997). Effect of 12-Month Dehydroepiandrosterone Replacement Therapy on Bone, Vagina, and Endometrium in Postmenopausal Women. J. Clin. Endocrinol. Metab.
82: 3498-3505
[Abstract][Full Text]
Danenberg, H. D., Ben-Yehuda, A., Zakay-Rones, Z., Gross, D. J., Friedman, G.
(1997). Dehydroepiandrosterone Treatment Is Not Beneficial to the Immune Response to Influenza in Elderly Subjects. J. Clin. Endocrinol. Metab.
82: 2911-2914
[Abstract][Full Text]
Lane, M. A., Ingram, D. K., Ball, S. S., Roth, G. S.
(1997). Dehydroepiandrosterone Sulfate: A Biomarker of Primate Aging Slowed by Calorie Restriction. J. Clin. Endocrinol. Metab.
82: 2093-2096
[Abstract][Full Text]
Barrett-Connor, E.
(1997). Sex Differences in Coronary Heart Disease: Why Are Women So Superior? The 1995 Ancel Keys Lecture. Circulation
95: 252-264
[Full Text]
Berr, C., Lafont, S., Debuire, B., Dartigues, J.-F., Baulieu, E.-E.
(1996). Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study. Proc. Natl. Acad. Sci. USA
93: 13410-13415
[Abstract][Full Text]
Weksler, M. E
(1996). Hormone replacement for men. BMJ
312: 859-860
[Full Text]
Metherall, J. E., Li, H., Waugh, K.
(1996). Role of Multidrug Resistance P-glycoproteins in Cholesterol Biosynthesis. J. Biol. Chem.
271: 2634-2640
[Abstract][Full Text]
Barbagallo, M., Shan, J., Pang, P. K.T., Resnick, L. M.
(1995). Effects of Dehydroepiandrosterone Sulfate on Cellular Calcium Responsiveness and Vascular Contractility. Hypertension
26: 1065-1069
[Abstract][Full Text]
Barrett-Connor, E., Goodman-Gruen, D.
(1995). Dehydroepiandrosterone Sulfate Does Not Predict Cardiovascular Death in Postmenopausal Women : The Rancho Bernardo Study. Circulation
91: 1757-1760
[Abstract][Full Text]
Mazat, L., Lafont, S., Berr, C., Debuire, B., Tessier, J.-F., Dartigues, J.-F., Baulieu, E.-E.
(2001). Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: Relationship to gender, subjective health, smoking habits, and 10-year mortality. Proc. Natl. Acad. Sci. USA
98: 8145-8150
[Abstract][Full Text]