The Significance of Dehydroepiandrosterone for Fatigue in primary Sjögren’s Syndrome and Systemic Lupus Erythematosus

Fatigue is a prevalent and debilitating symptom in patients with the chronic inflammatory autoimmune diseases primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE). Both diseases have a female preponderance (women to men ratio 9:1). Doctors recognize the existence of fatigue and its consequences, but are unable to treat it. The main objective of the studies described in this thesis was to study whether administration of DHEA has positive effects on fatigue, well-being and functioning in patients suffering from these conditions. The weak androgenic hormone DHEA is a product from the human adrenal glands. In peripheral tissues, the compound can be converted into active androgens and estrogens. Several studies reported that administration of DHEA to elderly people can improve age-related decreased vitality and fatigue, whereas positive effects have also been described in patients with depression, anorexia nervosa, chronic fatigue syndrome and Addison’s disease. In patients with pSS and SLE, serum levels of DHEA and its sulphate ester DHEAS not infrequently are decreased. This thesis evaluated the association between endogenous DHEA-S serum levels and fatigue and well-being in women with pSS and SLE in comparison to healthy female age-matched controls and examined in a randomized double-blind placebo-controlled study the effects of administration of DHEA 200 mg/day on fatigue, well-being, and functioning. We found that patients with pSS and SLE report, compared to healthy controls, far more general fatigue, depressed mood and reduced mental well-being and physical functioning. However, although DHEA-S serum levels in pSS and SLE patients were significantly lower compared to healthy controls, there was no significant correlation between DHEA-S level and these manifestations. Administration of exogenous DHEA to patients resulted, both in pSS and SLE patients, in significant improvement of fatigue and well-being. However, similar effects were found in patients who received placebo. The improvement of fatigue was associated more strongly with the belief to have used DHEA than with its actual use. Our studies indicate that complaints of fatigue and well-being can be reduced in a significant number of patients with SLE and pSS and illustrate the importance of the inclusion of placebo groups in clinical studies, in particular in those on subjective manifestations like fatigue. Unfortunately, our studies do not support use of DHEA to influence fatigue and well-being in patients with pSS and SLE. In contrast, our results support future studies on the effects of cognitive behavioral therapy.