{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:16:06Z","timestamp":1789881366575,"version":"4.0.1"},"reference-count":42,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,12,1]]},"abstract":"<jats:p>Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are adrenal precursors of steroid biosynthesis and centrally acting neurosteroids. Glucocorticoid and mineralocorticoid deficiencies in Addison\u2019s 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\u2019s 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\u0394 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\u2019s disease.<\/jats:p>","DOI":"10.1210\/jcem.85.12.7022","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:05:05Z","timestamp":1389200705000},"page":"4650-4656","source":"Crossref","is-referenced-by-count":15,"title":["Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison\u2019s Disease in a Randomized, Double Blind Trial"],"prefix":"10.1210","volume":"85","author":[{"given":"Penelope J.","family":"Hunt","sequence":"first","affiliation":[{"name":"Department of Endocrinology, University of Oxford, Radcliffe Infirmary (P.J.H., J.A.H.W.), Oxford, United Kingdom OX2 7JS, Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor M.","family":"Gurnell","sequence":"additional","affiliation":[{"name":"Departments of Medicine (E.M.G., C.R., V.K.K.C.), Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia A.","family":"Huppert","sequence":"additional","affiliation":[{"name":"Psychiatry (F.A.H.), Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Richards","sequence":"additional","affiliation":[{"name":"Departments of Medicine (E.M.G., C.R., V.K.K.C.), Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Toby","family":"Prevost","sequence":"additional","affiliation":[{"name":"Community Medicine (A.T.P.), Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A. H.","family":"Wass","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University of Oxford, Radcliffe Infirmary (P.J.H., J.A.H.W.), Oxford, United Kingdom OX2 7JS, Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Herbert","sequence":"additional","affiliation":[{"name":"Anatomy (J.H.), University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Krishna K.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Departments of Medicine (E.M.G., C.R., V.K.K.C.), Cambridge, United Kingdom CB2 2QQ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071618165127000_R1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1515\/bchm2.1934.229.4-6.192","article-title":"Isolierung neuen, physiologisch unwirksamen Sterindervates aus Mannerharn, Seine Verknupfung mit Dehdro-androsterone und Androsteron.","volume":"229","author":"Butenandt","year":"1934","journal-title":"Z Physiol Chem"},{"key":"2020071618165127000_R2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/0022-4731(87)90133-6","article-title":"Neuro-steroids: 3\u03b2-hydroxy-\u03945-derivatives in rat and monkey brain.","volume":"27","author":"Robel","year":"1987","journal-title":"J Steroid Biochem"},{"key":"2020071618165127000_R3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0006-8993(87)90807-9","article-title":"Effects of dehydroepiandrosterone and its sulfate on brain tissue in culture and on memory in mice.","volume":"406","author":"Roberts","year":"1987","journal-title":"Brain Res"},{"key":"2020071618165127000_R4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/jnr.490170305","article-title":"Dehydroepiandrosterone, its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures.","volume":"17","author":"Bologa","year":"1987","journal-title":"J Neurosci Res"},{"key":"2020071618165127000_R5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0006-8993(88)91129-8","article-title":"Dehydroepiandrosterone, its sulfate enhance memory retention in mice.","volume":"447","author":"Flood","year":"1988","journal-title":"Brain Res"},{"key":"2020071618165127000_R6","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1523\/JNEUROSCI.14-04-02047.1994","article-title":"Glucocorticoid-induced impairment in declarative memory performance in adult humans.","volume":"14","author":"Newcomer","year":"1994","journal-title":"J Neurosci"},{"key":"2020071618165127000_R7","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.715460","article-title":"Hippocampal aging and adrenocorticoids: quantitative correlations.","volume":"202","author":"Landfield","year":"1978","journal-title":"Science"},{"key":"2020071618165127000_R8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/271","article-title":"Cortisol levels during human aging predict hippocampal atrophy and memory deficits.","volume":"1","author":"Lupien","year":"1998","journal-title":"Nat Neurosci"},{"key":"2020071618165127000_R9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1001\/archinte.1981.00340020077021","article-title":"Neuropsychiatric manifestations of patients with Cushing\u2019s syndrome: relationship to cortisol and adrenocorticotrophic hormone levels.","volume":"141","author":"Starkman","year":"1981","journal-title":"Arch Intern Med"},{"key":"2020071618165127000_R10","first-page":"E210","article-title":"Dehydroepiandrosterone prevents dexamethasone-induced hypertension in rats","volume":"263","author":"Shafagoj","year":"1992","journal-title":"Am J Physiol."},{"key":"2020071618165127000_R11","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0306-4522(98)00347-9","article-title":"Dehydroepiandrosterone (DHEA) antagonises the neurotoxic effects of corticosterone, translocation of SAPK 3 in hippocampal primary cultures.","volume":"89","author":"Kimonides","year":"1999","journal-title":"Neuroscience"},{"key":"2020071618165127000_R12","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1210\/jcem-46-3-396","article-title":"The adrenarche: prolactin, gonadotropins, adrenal androgens and cortisol.","volume":"46","author":"Parker","year":"1978","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R13","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1210\/jcem-59-3-551","article-title":"Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood.","volume":"59","author":"Orentreich","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R14","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1056\/NEJM198612113152405","article-title":"A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease.","volume":"315","author":"Barrett-Connor","year":"1986","journal-title":"N Engl J Med"},{"key":"2020071618165127000_R15","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/S0140-6736(94)92587-9","article-title":"Physiological importance of dehydroepiandrosterone.","volume":"343","author":"Ebeling","year":"1994","journal-title":"Lancet"},{"key":"2020071618165127000_R16","first-page":"357","article-title":"Postmenopausal bone loss in rheumatoid arthritis: effect of estrogens and androgens.","volume":"19","author":"Sambrook","year":"1992","journal-title":"J Rheumatol"},{"key":"2020071618165127000_R17","first-page":"1360","article-title":"Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.","volume":"78","author":"Morales","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R18","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1046\/j.1365-2265.1998.00507.x","article-title":"The effect of six months treatment with a 100mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.","volume":"49","author":"Morales","year":"1998","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071618165127000_R19","first-page":"S43","article-title":"Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women","volume":"150","author":"Diamond","year":"1996","journal-title":"J Endocrinol."},{"key":"2020071618165127000_R20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0015-0282(98)00121-6","article-title":"Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-1 and decreases high-density lipoprotein: a six month trial.","volume":"70","author":"Casson","year":"1998","journal-title":"Fertil Steril"},{"key":"2020071618165127000_R21","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1210\/jcem.82.10.4306","article-title":"Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina and endometrium in postmenopausal women.","volume":"82","author":"Labrie","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R22","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1176\/ajp.156.4.646","article-title":"Double-blind treatment of major depression with dehydroepiandrosterone.","volume":"156","author":"Wolkowitz","year":"1999","journal-title":"Am J Psychiatry"},{"key":"2020071618165127000_R23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1055\/s-0029-1211215","article-title":"Quality of life in patients with Addison\u2019s disease: effects of different cortisol replacement modes.","volume":"101","author":"Reidel","year":"1993","journal-title":"Exp Clin Endocrinol"},{"key":"2020071618165127000_R24"},{"key":"2020071618165127000_R25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1677\/joe.0.1570081","article-title":"The effects of recombinant human IGF-1 administration on concentrations of acid labile subunit, IGF binding protein-3, IGF-1, IGF-II and proteolysis of IGF binding protein-3 in adolescents with insulin-dependent diabetes mellitus.","volume":"157","author":"Cheetham","year":"1998","journal-title":"J Endocrinol"},{"key":"2020071618165127000_R26","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1017\/S0033291700034644","article-title":"Adrenal secretion during major depression in 8- to 16- year olds. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation.","volume":"26","author":"Goodyer","year":"1996","journal-title":"Psychol Med"},{"key":"2020071618165127000_R27","first-page":"3951","article-title":"Cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age.","volume":"81","author":"Guazzo","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R28","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man.","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2020071618165127000_R29"},{"key":"2020071618165127000_R30","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1192\/bjp.155.2.178","article-title":"The factor structure of the General Health Questionnaire (GHQ-30): a reliability study on 6317 community residents.","volume":"155","author":"Huppert","year":"1989","journal-title":"Br J Psychiatry"},{"key":"2020071618165127000_R31","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF01542223","article-title":"The GRISS: a psychometric instrument for the assessment of sexual dysfunction.","volume":"15","author":"Rust","year":"1986","journal-title":"Arch Sex Behav"},{"key":"2020071618165127000_R32","author":"Pocock","year":"1983"},{"key":"2020071618165127000_R33","author":"Cox","year":"1987"},{"key":"2020071618165127000_R34","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1210\/jcem.83.6.4850","article-title":"Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young females after dexamethasone suppression.","volume":"83","author":"Arlt","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R35","first-page":"2578","article-title":"Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans.","volume":"82","author":"Young","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R36","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1210\/jcem.84.6.5789","article-title":"Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.","volume":"84","author":"Arlt","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R37","first-page":"1627","article-title":"Protection from glucocorticoid induced thymic involution by dehydroepiandrosterone.","volume":"46","author":"May","year":"1991","journal-title":"Life Sci"},{"key":"2020071618165127000_R38","first-page":"579","article-title":"Antiglucocorticoid action of dehydroepiandrosterone in young obese Zucker rats.","volume":"16","author":"Wright","year":"1992","journal-title":"Int J Obesity"},{"key":"2020071618165127000_R39","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1056\/NEJM199909303411401","article-title":"Dehydroepiandrosterone replacement in women with adrenal insufficiency.","volume":"341","author":"Arlt","year":"1999","journal-title":"N Engl J Med"},{"key":"2020071618165127000_R40","first-page":"227","article-title":"Clinical review: androgens and the postmenopausal woman.","volume":"21","author":"Davis","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R41","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1210\/jcem.83.10.5164","article-title":"A prospective study on cortisol, dehydroepiandrosterone sulfate and cognitive function in the elderly.","volume":"83","author":"Kalmijn","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618165127000_R42","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1073\/pnas.97.8.4279","article-title":"Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.","volume":"97","author":"Baulieu","year":"2000","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/85\/12\/4650\/9181988\/jcem4650.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/85\/12\/4650\/9181988\/jcem4650.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T14:56:08Z","timestamp":1688914568000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/85\/12\/4650\/2854033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12,1]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2000,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.85.12.7022","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12,1]]}}}