Endocrine Abstracts

In a double-blind study, 106 patients (44 males, 62 females, age 20-64 years) with Addison's disease, were randomised to receive either 50mg of micronised DHEA or placebo orally daily for 12 months. Psychological and biochemical parameters were measured at baseline, 3 to 6 month intervals and post-washout; bone mineral density (BMD) and body composition were assessed by DEXA at baseline and 12 months.

DHEAS levels rose significantly and were maintained throughout, with increased androstenedione in both sexes but elevation of testosterone to low normal only in females. Following DHEA, total body (p=0.03) and truncal lean mass (p=0.02) increased with no change in fat mass. DHEA increased BMD at the femoral neck with no effect at other sites. At baseline, subscales of the Short Form (SF-36) health survey and General Health Questionnaire (GHQ-30) were significantly worse in subjects with Addison's disease versus control populations (SF-36; role physical, general health, vitality, role emotional; GHQ-30: total score, anxiety, self-esteem (p<0.001)). Following DHEA, mood and general well-being improved and fatigue lessened significantly (p=0.03) at 3 and 6 months; conversely, after washout of DHEA at the end, some indices deteriorated markedly (GHQ-30: total score p=0.03, self-esteem p<0.001, coping p=0.002; SF-36 role physical p=0.04, role emotional p=0.004). There was no consistent effect on sexual function. With exceptions (increase in proximal radius BMD (p=0.03) and worsening of SF-36 subscale post-washout (p=0.02) greater in males), there were no gender-specific differences in effects of DHEA. Supraphysiological DHEAS levels were achieved in 53% of females with significant androgenic effects (spots, greasy skin, axillary hair growth).

DHEA replacement corrects this hormone deficiency in Addison's disease, with improvement in psychological function and enhancement of lean body mass and femoral neck BMD. Longer term studies, with adjustment of DHEA dosage, will establish whether there are cumulative beneficial effects and evaluate its long-term safety.