Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial

Abstract

Context: Adrenal derived androgens are low in women with adrenal failure. The physiological consequences of substitution therapy are uncertain. Objective: To investigate the effects of DHEA substitution in women with adrenal failure on body composition, fuel metabolism, and inflammatory markers. Design, participants and intervention: In this study, ten female patients (median age 38.5 years, range 28-52) with adrenal failure were treated with DHEA 50 mg for 6 months in a double-blind, randomized, placebo-controlled, and crossover study. The participants underwent dual-energy X-ray absorptiometry (DXA) scan, computed tomography scan of abdominal fat, indirect calorimetry, bicycle ergometry, muscle and fat biopsies, and blood samples. Results: Baseline androgens were normalized to fertile range during active treatment. Anthropometric data were unaffected, but lean body mass (LBM) slightly increased compared with placebo (delta LBM (kg) placebo versus DHEA: K0.48G6.1 vs 1.6G3.4, PZ0.02) with no alterations in total or abdominal fat mass. PTH increased with DHEA, but no significant changes were observed in other bone markers or in bone mineral content. The mRNA levels of markers of tissue inflammation (adiponectin, interleukin 6 (IL6), IL10, monocyte chemoattractant protein 1, and tumor necrosis factor a) in fat and muscle tissue were unaffected by DHEA treatment, as was indirect calorimetry and maximal oxygen uptake. A high proportion of self-reported seborrheic side effects were recorded (60%). Conclusion: In female adrenal failure, normalization of androgens with DHEA 50 mg for 6 months had no effects on muscle, fat, and bone tissue and on fuel metabolism in this small study. A small increase in LBM was observed. Treatment was associated with a high frequency of side effects.

Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines

“…In vivo, lower androgen levels may contribute to sexual dimorphism of circulating adipokine levels, which was also demonstrated in our healthy and affected cohorts [ 39 , 54 , 55 , 61 ]. These results add up to the current discussion concerning metabolic benefits of the DHEA replacement in adrenal failure, which remain controversial despite several randomized trials [ 53 , 62 , 63 ].…”

Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men

“…Six-month DHEAS treatment in women with adrenal insufficiency did not affect MCP-1 levels despite increased LBM [27], but fat distribution was unchanged and MIF data were not available in the study. Interestingly, animal studies showed that rats express MIF in Leydig cells, but whether MIF affects human reproduction is undetermined [25, 28].…”

Effects of dehydroepiandrosterone (DHEA) supplementation on cortisol, leptin, adiponectin, and liver enzyme levels: A systematic review and meta‐analysis of randomised clinical trials

“…We deleted 1930 duplicates, then 3283 articles were eliminated according to the title and abstract of the trials. In the next stage, 217 trials based on the full text were surveyed and lastly 14 articles with 10 arms on cortisol, [22][23][24][25][26][27][28][29][30] 5 articles with 6 arms on adiponectin, 9,27,28,31,32 2 articles with 3 arms on leptin, 9,31 2 articles with 3 arms on AST 9,32 and 4 articles with 5 arms on ALT 12,[32][33][34] (Figure 1). Table 1 lists the characteristics of 14 included articles.…”