In the present study, we found decreased DHEAS concentrations in both women and men with RA, Spa, or UIA. This finding was previously documented in RA . With regard to Spa, Hedman et al  reported normal DHEAS concentrations in 25 patients who had psoriatic arthritis, reactive arthritis, ankylosing spondylitis, or enteropathic arthritis. Both elevated and decreased DHEAS concentrations have been reported in ankylosing spondylitis [19,20]. In one of the latter reports, a significant correlation between low DHEAS concentrations and a high acute-phase response was found , as was recently reported for RA . The role of sex steroids in the pathogenesis of Spa remains incompletely elucidated . Of our 29 patients with Spa, 9 had ankylosing spondylitis, 7 psoriatic arthritis, and 13 reactive or undifferentiated spondyloarthropathy. Although the DHEAS concentrations were highest in our patients with MSpa, the respective concentrations were still significantly lower than in age- and gender-matched controls.
The number of patients enrolled in our study allowed us to control for disease-related factors, i.e. the acute-phase response, previous glucocorticoid usage, NSAID treatment, duration of disease, and insulin resistance. The overall disease activity was low in our patients (mean ESR=26 mm/hour), which may explain why the investigated disease-related parameters did not significantly predict low DHEAS concentrations except for previous glucocorticoid usage in RA women and NSAID treatments in IA men. Even after disease-related factors were controlled for, DHEAS concentrations tended to remain lower in IA women than in their control subjects. This finding indirectly supports the intriguing paradigm in which IA may select for patients with subtle adrenal insufficiency, as proposed by Masi et al . Our finding of similarly decreased concentrations in the various subsets of the disease supports the observation that risk factors for RA and inflammatory arthritides other than RA are alike . In contrast, DHEAS concentrations were no longer different in men with IA from those in their controls after disease-related parameters had been controlled for. Underactivity of the hypothalamic–pituitary–gonadal axis, with decreased testosterone production, was documented in men with RA , and this underactivity may participate in the pathogenesis in these patients . The roles of hypoadrenalism (decreased glucocorticoid as well as adrenal androgen production) and hypogonadism in the onset and persistence of disease in various IA subgroups and in both genders deserves further investigation.
In 44 (51%) of our patients, serum DHEAS concentrations were below the 25th percentile obtained in controls and in 24 patients (28%), these levels were below normal. Robinzon and Cutolo  recently attributed several side effects of glucocorticoid therapy, including catabolism, muscular atrophy, osteopenia, osteoporosis, and avascular necrosis, to the suppressant effect of these agents on the hypothalamic–pituitary–adrenal axis, resulting in decreased DHEA secretion. Also, low DHEAS concentrations constitute an independent risk factor for cardiovascular disease  and recently DHEA was shown to form an intergral part of low-density lipoprotein and to protect the latter potently from oxidation . This is of interest in the present context, since a 70% excess cardiovascular mortality was reported in RA [24–26]. Indeed, IA and cardiovascular disease may share a common predisposition .
DHEA replacement is associated with improvement of physical and general wellbeing in elderly subjects  and with lessening of disease activity in lupus  and of osteoporosis in postmenopausal women . It constitutes part of the optimal treatment of frank adrenal insufficiency . Robinzon and Cutolo suggested the use of DHEA replacement, guided by monitoring of its concentration in the blood, in RA patients taking glucocorticoids . Although short-term DHEA replacement therapy was not associated with an improvement in disease activity in 11 patients with RA, the findings mentioned above together with our results suggest that the indications for DHEA replacement in IA should not be restricted to patients on glucocorticoids. The role of DHEA supplementation in the treatment of IA requires further study.