Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial
Open Access
- 1 February 2008
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 93 (2), 400-409
- https://doi.org/10.1210/jc.2007-1134
Abstract
Context: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison’s disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. Objective and Design: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison’s disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. Results: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison’s patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects. Conclusion: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison’s disease.Keywords
This publication has 55 references indexed in Scilit:
- Dehydroepiandrosterone supplementation in women with adrenal failure: impact on twenty-four hour GH secretion and IGF-related parametersClinical Endocrinology, 2004
- Differential Gene Expression Profile of Glucocorticoids, Testosterone, and Dehydroepiandrosterone in Human CellsHormone and Metabolic Research, 2001
- Dehydroepiandrosterone Replacement in Women with Adrenal InsufficiencyThe New England Journal of Medicine, 1999
- Double dissociations of memory and executive functions in working memory tasks following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in manBrain, 1996
- The Factor Structure of the General Health Questionnaire (GHQ-30)The British Journal of Psychiatry, 1989
- Integrating clinical assessment with cognitive neuroscience: Construct validation of the California Verbal Learning Test.Journal of Consulting and Clinical Psychology, 1988
- Integrating clinical assessment with cognitive neuroscience: Construct validation of the California Verbal Learning Test.Journal of Consulting and Clinical Psychology, 1988
- Neuro-steroids: 3β-hydroxy-δ5-derivatives in rat and monkey brainJournal of Steroid Biochemistry, 1987
- A Prospective Study of Dehydroepiandrosterone Sulfate, Mortality, and Cardiovascular DiseaseThe New England Journal of Medicine, 1986
- Fornix lesions selectively abolish place learning in the ratExperimental Neurology, 1975