DHEA in Elderly Women and DHEA or Testosterone in Elderly Men
K. Sreekumaran Nair, M.D., Ph.D., Robert A. Rizza, M.D., Peter O'Brien, Ph.D., Ketan Dhatariya, M.D., M.R.C.P., Kevin R. Short, Ph.D., Ajay Nehra, M.D., Janet L. Vittone, M.D., George G. Klee, M.D., Ananda Basu, M.D., Rita Basu, M.D., Claudio Cobelli, Ph.D., Gianna Toffolo, Ph.D., Chiara Dalla Man, Ph.D., Donald J. Tindall, Ph.D., L. Joseph Melton, III, M.D., Ph.D., Glenn E. Smith, Ph.D., Sundeep Khosla, M.D., and Michael D. Jensen, M.D.
Background Dehydroepiandrosterone (DHEA) and testosterone arewidely promoted as antiaging supplements, but the long-termbenefits, as compared with potential harm, are unknown.
Methods We performed a 2-year, placebo-controlled, randomized,double-blind study involving 87 elderly men with low levelsof the sulfated form of DHEA and bioavailable testosterone and57 elderly women with low levels of sulfated DHEA. Among themen, 29 received DHEA, 27 received testosterone, and 31 receivedplacebo. Among the women, 27 received DHEA and 30 received placebo.Outcome measures included physical performance, body composition,bone mineral density (BMD), glucose tolerance, and quality oflife.
Results As compared with the change from baseline to 24 monthsin the placebo group, subjects who received DHEA for 2 yearshad an increase in plasma levels of sulfated DHEA by a medianof 3.4 µg per milliliter (9.2 µmol per liter) inmen and by 3.8 µg per milliliter (10.3 µmol perliter) in women. Among men who received testosterone, the levelof bioavailable testosterone increased by a median of 30.4 ngper deciliter (1.1 nmol per liter), as compared with the changein the placebo group. A separate analysis of men and women showedno significant effect of DHEA on body-composition measurements.Neither hormone altered the peak volume of oxygen consumed perminute, muscle strength, or insulin sensitivity. Men who receivedtestosterone had a slight increase in fat-free mass, and menin both treatment groups had an increase in BMD at the femoralneck. Women who received DHEA had an increase in BMD at theultradistal radius. Neither treatment improved the quality oflife or had major adverse effects.
Conclusions Neither DHEA nor low-dose testosterone replacementin elderly people has physiologically relevant beneficial effectson body composition, physical performance, insulin sensitivity,or quality of life. (ClinicalTrials.gov number, NCT00254371
[ClinicalTrials.gov]
.)
Source Information
From the Division of Endocrinology (K.S.N., R.A.R., K.D., K.R.S., A.B., R.B., S.K., M.D.J.) and the Departments of Health Sciences Research (P.O., L.J.M.), Urology (A.N., D.J.T.), Medicine (J.L.V.), Laboratory Medicine and Pathology (G.G.K.), and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and the Department of Information Engineering, University of Padua, Padua, Italy (C.C., G.T., C.D.M.). Drs. Khosla and Jensen contributed equally to this article.
Address reprint requests to Dr. Nair at the Division of Endocrinology, Mayo Clinic, 200 First St. SW, 5-194 Joseph, Rochester, MN 55905, or at nair.sree{at}mayo.edu.
DHEA and Testosterone in the Elderly
Page S. T., Matsumoto A. M., Bremner W. J., Yasuda M., Horie S., Perls T. T., Gleicher N., Barad D., Nair K. S., Smith G.
Extract |
Full Text |
PDF
N Engl J Med 2007;
356:635-637, Feb 8, 2007.
Correspondence
This article has been cited by other articles:
Hardy, R, Cooper, M S
(2009). Bone loss in inflammatory disorders. J Endocrinol
201: 309-320
[Abstract][Full Text]
Sattler, F. R., Castaneda-Sceppa, C., Binder, E. F., Schroeder, E. T., Wang, Y., Bhasin, S., Kawakubo, M., Stewart, Y., Yarasheski, K. E., Ulloor, J., Colletti, P., Roubenoff, R., Azen, S. P.
(2009). Testosterone and Growth Hormone Improve Body Composition and Muscle Performance in Older Men. J. Clin. Endocrinol. Metab.
94: 1991-2001
[Abstract][Full Text]
Colangelo, L. A., Ouyang, P., Liu, K., Kopp, P., Golden, S. H., Dobs, A. S., Szklo, M., Vaidya, D., Cushman, M., Gapstur, S. M.
(2009). Association of Endogenous Sex Hormones With Diabetes andImpaired Fasting Glucose in Men: Multi-Ethnic Study of Atherosclerosis. Diabetes Care
32: 1049-1051
[Abstract][Full Text]
Henderson, G. C., Irving, B. A., Nair, K. S.
(2009). Potential Application of Essential Amino Acid Supplementation to Treat Sarcopenia in Elderly People. J. Clin. Endocrinol. Metab.
94: 1524-1526
[Full Text]
Legros, J.-J., Meuleman, E. J H, Elbers, J. M H, Geurts, T B P., Kaspers, M. J G H, Bouloux, P. M G, for the Study 43203 Investigators,
(2009). Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Eur J Endocrinol
160: 821-831
[Abstract][Full Text]
Weiss, E. P, Shah, K., Fontana, L., Lambert, C. P, Holloszy, J. O, Villareal, D. T
(2009). Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am. J. Clin. Nutr.
89: 1459-1467
[Abstract][Full Text]
Srinivasan, M., Irving, B. A., Dhatariya, K., Klaus, K. A., Hartman, S. J., McConnell, J. P., Nair, K. S.
(2009). Effect of Dehydroepiandrosterone Replacement on Lipoprotein Profile in Hypoadrenal Women. J. Clin. Endocrinol. Metab.
94: 761-764
[Abstract][Full Text]
Henderson, G. C., Dhatariya, K., Ford, G. C., Klaus, K. A., Basu, R., Rizza, R. A., Jensen, M. D., Khosla, S., O'Brien, P., Nair, K. S.
(2009). Higher muscle protein synthesis in women than men across the lifespan, and failure of androgen administration to amend age-related decrements. FASEB J.
23: 631-641
[Abstract][Full Text]
Cappola, A. R., Xue, Q.-L., Fried, L. P.
(2009). Multiple Hormonal Deficiencies in Anabolic Hormones Are Found in Frail Older Women: The Women's Health and Aging Studies. J Gerontol A Biol Sci Med Sci
64A: 243-248
[Abstract][Full Text]
Jankowski, C. M., Gozansky, W. S., Kittelson, J. M., Van Pelt, R. E., Schwartz, R. S., Kohrt, W. M.
(2008). Increases in Bone Mineral Density in Response to Oral Dehydroepiandrosterone Replacement in Older Adults Appear to Be Mediated by Serum Estrogens. J. Clin. Endocrinol. Metab.
93: 4767-4773
[Abstract][Full Text]
Dhatariya, K. K., Greenlund, L. J. S., Bigelow, M. L., Thapa, P., Oberg, A. L., Ford, G. C., Schimke, J. M., Nair, K. S.
(2008). Dehydroepiandrosterone Replacement Therapy in Hypoadrenal Women: Protein Anabolism and Skeletal Muscle Function. Mayo Clin Proc.
83: 1218-1225
[Abstract][Full Text]
Chen, H., Lin, A. S., Li, Y., Reiter, C. E. N., Ver, M. R., Quon, M. J.
(2008). Dehydroepiandrosterone Stimulates Phosphorylation of FoxO1 in Vascular Endothelial Cells via Phosphatidylinositol 3-Kinase- and Protein Kinase A-dependent Signaling Pathways to Regulate ET-1 Synthesis and Secretion. J. Biol. Chem.
283: 29228-29238
[Abstract][Full Text]
Singh, M., Alexander, K., Roger, V. L., Rihal, C. S., Whitson, H. E., Lerman, A., Jahangir, A., Nair, K. S.
(2008). Frailty and Its Potential Relevance to Cardiovascular Care. Mayo Clin Proc.
83: 1146-1153
[Abstract][Full Text]
Penisson-Besnier, I., Devillers, M., Porcher, R., Orlikowski, D., Doppler, V., Desnuelle, C., Ferrer, X., Bes, M. -C.A., Bouhour, F., Tranchant, C., Lagrange, E., Vershueren, A., Uzenot, D., Cintas, P., Sole, G., Hogrel, J. -Y., Laforet, P., Vial, C., Vila, A. L., Sacconi, S., Pouget, J., Eymard, B., Chevret, S., Annane, D.
(2008). Dehydroepiandrosterone for myotonic dystrophy type 1. Neurology
71: 407-412
[Abstract][Full Text]
Giannoulis, M. G., Jackson, N., Shojaee-Moradie, F., Nair, K. S., Sonksen, P. H., Martin, F. C., Umpleby, A. M.
(2008). The Effects of Growth Hormone and/or Testosterone on Whole Body Protein Kinetics and Skeletal Muscle Gene Expression in Healthy Elderly Men: A Randomized Controlled Trial. J. Clin. Endocrinol. Metab.
93: 3066-3074
[Abstract][Full Text]
Dhatariya, K.
(2008). Dehydroepiandrosterone Sulfate Has Not Been Substantiated as an Anabolic Hormone. Arch Intern Med
168: 1470-1470
[Full Text]
Maggio, M., Ceda, G. P., Basaria, S., Valenti, G., Ferrucci, L.
(2008). Dehydroepiandrosterone Sulfate Has Not Been Substantiated as an Anabolic Hormone--Reply. Arch Intern Med
168: 1470-1470
[Full Text]
Cappola, A. R., Maggio, M., Ferrucci, L.
(2008). Is Research on Hormones and Aging Finished? No! Just Started!. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
63: 696-698
[Full Text]
Page, J. H., Ma, J., Rexrode, K. M., Rifai, N., Manson, J. E., Hankinson, S. E.
(2008). Plasma Dehydroepiandrosterone and Risk of Myocardial Infarction in Women. Clin. Chem.
54: 1190-1196
[Abstract][Full Text]
Khosla, S., Amin, S., Orwoll, E.
(2008). Osteoporosis in Men. Endocr. Rev.
29: 441-464
[Abstract][Full Text]
Knapp, P. E., Storer, T. W., Herbst, K. L., Singh, A. B., Dzekov, C., Dzekov, J., LaValley, M., Zhang, A., Ulloor, J., Bhasin, S.
(2008). Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Am. J. Physiol. Endocrinol. Metab.
294: E1135-E1143
[Abstract][Full Text]
Paddon-Jones, D., Short, K. R, Campbell, W. W, Volpi, E., Wolfe, R. R
(2008). Role of dietary protein in the sarcopenia of aging. Am. J. Clin. Nutr.
87: 1562S-1566S
[Abstract][Full Text]
Burt, M. G., Johannsson, G., Umpleby, A. M., Chisholm, D. J., Ho, K. K. Y.
(2008). Impact of Growth Hormone and Dehydroepiandrosterone on Protein Metabolism in Glucocorticoid-Treated Patients. J. Clin. Endocrinol. Metab.
93: 688-695
[Abstract][Full Text]
Gurnell, E. M., Hunt, P. J., Curran, S. E., Conway, C. L., Pullenayegum, E. M., Huppert, F. A., Compston, J. E., Herbert, J., Chatterjee, V. K. K.
(2008). Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial. J. Clin. Endocrinol. Metab.
93: 400-409
[Abstract][Full Text]
Igwebuike, A., Irving, B. A., Bigelow, M. L., Short, K. R., McConnell, J. P., Nair, K. S.
(2008). Lack of Dehydroepiandrosterone Effect on a Combined Endurance and Resistance Exercise Program in Postmenopausal Women. J. Clin. Endocrinol. Metab.
93: 534-538
[Abstract][Full Text]
Allan, C. A., Strauss, B. J. G., Burger, H. G., Forbes, E. A., McLachlan, R. I.
(2008). Testosterone Therapy Prevents Gain in Visceral Adipose Tissue and Loss of Skeletal Muscle in Nonobese Aging Men. J. Clin. Endocrinol. Metab.
93: 139-146
[Abstract][Full Text]
Hartkamp, A, Geenen, R, Godaert, G L R, Bootsma, H, Kruize, A A, Bijlsma, J W J, Derksen, R H W M
(2008). Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome: a randomised controlled trial. Ann Rheum Dis
67: 91-97
[Abstract][Full Text]
Khaw, K.-T., Dowsett, M., Folkerd, E., Bingham, S., Wareham, N., Luben, R., Welch, A., Day, N.
(2007). Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men: European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation
116: 2694-2701
[Abstract][Full Text]
Maggio, M., Lauretani, F., Ceda, G. P., Bandinelli, S., Ling, S. M., Metter, E. J., Artoni, A., Carassale, L., Cazzato, A., Ceresini, G., Guralnik, J. M., Basaria, S., Valenti, G., Ferrucci, L.
(2007). Relationship Between Low Levels of Anabolic Hormones and 6-Year Mortality in Older Men: The Aging in the Chianti Area (InCHIANTI) Study. Arch Intern Med
167: 2249-2254
[Abstract][Full Text]
Reuben, D. B.
(2007). Update in Geriatric Medicine. ANN INTERN MED
147: 470-477
[Full Text]
Basu, R., Man, C. D., Campioni, M., Basu, A., Nair, K. S., Jensen, M. D., Khosla, S., Klee, G., Toffolo, G., Cobelli, C., Rizza, R. A.
(2007). Effect of 2 Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance, and Postprandial Glucose Turnover in Elderly Men. Diabetes Care
30: 1972-1978
[Abstract][Full Text]
Harrington, D. W., Munekata, M. T.
(2007). Update in General Internal Medicine. ANN INTERN MED
147: 104-116
[Full Text]
Cobelli, C., Toffolo, G. M., Man, C. D., Campioni, M., Denti, P., Caumo, A., Butler, P., Rizza, R.
(2007). Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am. J. Physiol. Endocrinol. Metab.
293: E1-E15
[Abstract][Full Text]
Basu, R., Dalla Man, C., Campioni, M., Basu, A., Nair, K. S., Jensen, M. D., Khosla, S., Klee, G., Toffolo, G., Cobelli, C., Rizza, R. A.
(2007). Two Years of Treatment With Dehydroepiandrosterone Does Not Improve Insulin Secretion, Insulin Action, or Postprandial Glucose Turnover in Elderly Men or Women. Diabetes
56: 753-766
[Abstract][Full Text]
Page, S. T., Matsumoto, A. M., Bremner, W. J., Yasuda, M., Horie, S., Perls, T. T., Gleicher, N., Barad, D., Nair, K. S., Smith, G.
(2007). DHEA and Testosterone in the Elderly. NEJM
356: 635-637
[Full Text]
(2007). Other articles noted. Evid. Based Med.
12: 31-32
[Full Text]
(2006). Endocrinology & Metabolism News November 2006. J. Clin. Endocrinol. Metab.
91: 17a-17a
[Full Text]
Stewart, P. M.
(2006). Aging and Fountain-of-Youth Hormones. NEJM
355: 1724-1726
[Full Text]
(2006). DHEA and Testosterone Supplementation: No Anti-Aging Benefits for Older Adults. JWatch General
2006: 1-1
[Full Text]