Serum levels of the sex steroid prohormones dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) decline upon aging and are reduced in primary Sjogren's syndrome. Our aim was to investigate: 1) effects of 50 mg oral DHEA/day on changes in serum levels of DHEA and 12 of its metabolites; 2) relationships between steroid levels and disease characteristics; and 3) whether these parameters were influenced by DHEA. Twenty-three postmenopausal women with primary Sjogren's syndrome and subnormal levels of DHEA-S were included in a randomized, 9-month, controlled, double blind crossover study. Liquid chromatography/mass spectrometry (MS)/MS and gas chromatography/MS were used to measure the sex steroids. Anti-SS-A/Ro and/or anti-SS-B/La, salivary gland focus score, salivary flow rates, dry mouth and eye symptoms, and routine laboratory tests were assessed. Baseline erythrocyte sedimentation rate was inversely correlated with testosterone (Testo), dihydrotestosterone, and DHEA-S (rs = -0.42, -0.45, and -0.58, respectively). Dry mouth symptoms correlated with low Testo and androstenedione, whereas dry eyes correlated with low estrogens, most strongly estrone (rs = -0.63). Presence of anti-SS-A and/or anti-SS-B was independently associated with low estradiol (area under the receiver operating characteristic curve, 0.82). All metabolites increased during DHEA but not during placebo. The relative increases were less for estrogens and Testo compared to dihydrotestosterone and glucuronidated androgen metabolites. Dry mouth symptoms decreased during DHEA therapy. Disease manifestations in primary Sjogren's syndrome were associated with low sex hormone levels, dry mouth symptoms with low androgens, and dry eyes with low estrogens. Exogenous DHEA was preferentially transformed into androgens rather than into estrogens.
