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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 12 4650-4656
Copyright © 2000 by The Endocrine Society

Original Studies

Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison’s Disease in a Randomized, Double Blind Trial

Penelope J. Hunt1,2, Eleanor M. Gurnell1,3, Felicia A. Huppert, Christine Richards, A. Toby Prevost, John A. H. Wass, Joseph Herbert and V. Krishna K. Chatterjee4

Department of Endocrinology, University of Oxford, Radcliffe Infirmary (P.J.H., J.A.H.W.), Oxford, United Kingdom OX2 7JS; and Departments of Medicine (E.M.G., C.R., V.K.K.C.), Psychiatry (F.A.H.), Community Medicine (A.T.P.), and Anatomy (J.H.), University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom CB2 2QQ

Address all correspondence and requests for reprints to: Prof. Krishna Chatterjee, Department of Medicine, Level 5, Addenbrooke’s Hospital, Hills Road, Cambridge, United Kingdom CB2 2QQ. E-mail: kkc1{at}mole.bio.cam.ac.uk

Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are adrenal precursors of steroid biosynthesis and centrally acting neurosteroids. Glucocorticoid and mineralocorticoid deficiencies in Addison’s disease require life-long hormone replacement, but the associated failure of DHEA synthesis is not corrected. We conducted a randomized, double blind study in which 39 patients with Addison’s disease received either 50 mg oral DHEA daily for 12 weeks, followed by a 4-week washout period, then 12 weeks of placebo, or vice versa. After DHEA treatment, levels of DHEAS and {Delta}4-androstenedione rose from subnormal to within the adult physiological range. Total testosterone increased from subnormal to low normal with a fall in serum sex hormone-binding globulin in females, but with no change in either parameter in males. In both sexes, psychological assessment showed significant enhancement of self-esteem with a tendency for improved overall well-being. Mood and fatigue also improved significantly, with benefit being evident in the evenings. No effects on cognitive or sexual function, body composition, lipids, or bone mineral density were observed. Our results indicate that DHEA replacement corrects this steroid deficiency effectively and improves some aspects of psychological function. Beneficial effects in males, independent of circulating testosterone levels, suggest that it may act directly on the central nervous system rather than by augmenting peripheral androgen biosynthesis. These positive effects, in the absence of significant adverse events, suggest a role for DHEA replacement therapy in the treatment of Addison’s disease.




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