Long-term DHEA replacement in primary adrenal insufficiency: A randomized, controlled trial

被引:137
作者
Gurnell, Eleanor M. [1 ]
Hunt, Penelope J. [3 ]
Curran, Suzanne E. [1 ]
Conway, Catherine L. [3 ]
Pullenayegum, Eleanor M.
Huppert, Felicia A.
Compston, Juliet E. [1 ]
Herbert, Joseph [2 ]
Chatterjee, V. Krishna K. [1 ]
机构
[1] Addenbrookes Hosp, Dept Med, Univ Cambridge, Cambridge CB2 0QQ, England
[2] Addenbrookes Hosp, Dept Anat, Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 0QQ, England
[3] Christchurch Hosp, Dept Endocrinol, Christchurch 8140, New Zealand
基金
英国惠康基金; 英国医学研究理事会;
关键词
SUBJECTIVE HEALTH-STATUS; BONE-MINERAL DENSITY; DEHYDROEPIANDROSTERONE DHEA; POSTMENOPAUSAL WOMEN; ADDISONS-DISEASE; ELDERLY-WOMEN; MEN; SULFATE; RAT; TESTOSTERONE;
D O I
10.1210/jc.2007-1134
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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 5F-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.
引用
收藏
页码:400 / 409
页数:10
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