The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison’s Disease in a Randomized, Double Blind Trial
Abstract
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 biosynthesi…
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“In addition, some (but not all) studies have shown that DHEA replacement in adrenal insufficiency may improve HRQoL and mood, with reduced depression and anxiety scores (114 -116).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [115]
In the citing paper
“Our previous placebo-controlled 3-month crossover trial of 39 patients (including 15 males) with primary adrenal insufficiency showed similar biochemical changes and enhanced psychological well-being, independent of gender (20).”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“score significantly worse than age-and sexmatched population controls on validated psychological tests that measure well-being (20,21).”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“No changes in body composition, BMD or cognition were demonstrated in any of these short-term studies of DHEA replacement.”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“This 12-month study of DHEA replacement in patients with Addison's disease both supports the improved well-being documented in our previous short-term study and adds new information on longer-term effects of DHEA.”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“The hormone profile of DHEA-treated subjects was similar to that observed in our previous study (20) with significant increases in androstenedione in both sexes and testosterone in women but not in men.”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“Twenty-three subjects had taken part in our previous, short-term trial of DHEA (20) but were distributed comparably across DHEA (n ϭ 9) and placebo (n ϭ 14) groups.”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“which is in keeping with observations in some short- (20,48,54) and longer-term trials (25) but differs from observations in women with primary or secondary adrenal failure (23,24).”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“Despite earlier reports suggesting changes in IGF-I with DHEA replacement, both our earlier short-term trial (20) and the present study showed no statistically significant change in circulating IGF-I levels, in agreement with another recent replacement study (50), arguing against a primary role of this hormone in mediating increases in lean muscle mass.”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“Interestingly, similar abnormalities in the self-esteem subscale of GHQ-30 occurred in both of our studies [this one and an earlier shorter-term replacement study (20)]”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
In the citing paper
“suggesting there may be a disorderspecific profile of psychological deficit in Addison's disease.”
From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [20]
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Background
Metadata
- Authors
- Hunt, P. J., Gurnell, E. M., Huppert, F. A., Richards, C., Prevost, A. T., Wass, J. A. H., Herbert, J., & Chatterjee, V. K. K.
- Affiliations
- University of Oxford (GB)
- University of Cambridge (GB)
- Community Medicine (A.T.P.), Cambridge, United Kingdom CB2 2QQ
- Departments of Medicine (E.M.G., C.R., V.K.K.C.), Cambridge, United Kingdom CB2 2QQ
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2000-12-01
- Volume
- 85
- Issue
- 12
- Pages
- 4650-4656
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2138758697
- Cited by
- 386
- References
- 45
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 8 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 58 · 2019: 1 · 2018: 7 · 2017: 4 · 2016: 10 · 2015: 13 · 2014: 15 · 2013: 5 · 2012: 12
- FWCI
- 16.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Hologic
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- dehydroepiandrosterone, Addison's disease, DHEA replacement therapy, DHEA sulfate, adrenal insufficiency, mood, fatigue, self-esteem, well-being, testosterone, sex hormone-binding globulin, androstenedione, neurosteroids, central nervous system effects, glucocorticoid deficiency, mineralocorticoid deficiency
- MeSH terms
- Addison Disease, Adult, Affect, Aged, Body Composition, Cognition, Dehydroepiandrosterone, Double-Blind Method, Fatigue, Female, Hormones, Humans, Male, Middle Aged, Sexual Behavior, Bone Density, Cross-Over Studies, Dehydroepiandrosterone Sulfate, Hormone Replacement Therapy
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