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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 7 2363-2367
Copyright © 1997 by The Endocrine Society

Clinical Studies

Effects of a Two-Week Physiological Dehydroepiandrosterone Substitution on Cognitive Performance and Well-Being in Healthy Elderly Women and Men1

Oliver T. Wolf, Oliver Neumann, DIRK H. HELLHAMMER, Andrea C. Geiben, Christian J. Strasburger, Regina A. Dressendörfer, Karl-Martin Pirke and Clemens Kirschbaum

Center for Psychobiological and Psychosomatic Research, University of Trier (O.T.W., O.N., A.C.G.,K.-M.P., D.H.H., C.K.), Trier; and the Department of Internal Medicine, University of Munich Medical School, Klinik Innenstadt (C.J.S., R.A.D.), Munich, Germany

Address all correspondence and requests for reprints to: Dr. Clemens Kirschbaum, Center for Psychobiological and Psychosomatic Research, University of Trier, Dietrichstrasse 10–11, 54290 Trier, Germany. E-mail: kirschba{at}uni-trier.de

The levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS decrease with age after a peak around 25 yr. Animal studies as well as the first studies in humans have generated the idea that DHEA replacement in elderly subjects may have beneficial effects on well-being and cognitive functions. In the present experiment 40 healthy elderly men and women (mean age, 69 yr) participated in a double blind, placebo-controlled DHEA substitution study. For 2 weeks subjects took 50 mg DHEA daily, followed by a 2-week wash-out period and a 2-week placebo period. The treatment sequence was randomized in a cross-over design. After 2 weeks of DHEA or placebo, psychological and physical well-being as well as cognitive performance were assessed using several questionnaires and neuropsychological tests. All subjects had low DHEAS baseline levels. DHEA substitution lead to a 5-fold increase in DHEAS levels in women (from 0.67 ± 0.1 to 4.1 ± 0.4 µg/mL; P < 0.001) and men (from 0.85 ± 0.1 to 4.5 ± 0.4 µg/mL; P < 0.001). DHEA, androstenedione, and testosterone levels also increased significantly in both sexes (all P < 0.001). No significant changes were observed in insulin-like growth factor I or insulin-like growth factor-binding protein-3 levels.

DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters. Only women tended to report an increase in well-being (P = 0.11) and mood (P = 0.10), as assessed with questionnaires. They also showed better performance in one of six cognitive tests (picture memory) after DHEA. However, after Bonferroni {alpha} adjustment, this difference was no longer significant. No such trend was observed in men (P > 0.20). Likewise, no beneficial effects of DHEA substitution could be observed in any of the other tests of the neuropsychological test battery in either sex (all P > 0.20). In conclusion, the present data do not support the idea of strong beneficial effects of a physiological DHEA substitution on well-being or cognitive performance in healthy elderly individuals.




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