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Low Serum Levels of Sex Steroids Are Associated with Disease Characteristics in Primary Sjogren’s Syndrome; Supplementation with Dehydroepiandrosterone Restores the Concentrations

Department of Rheumatology and Inflammation Research (H.F.-d’E., H.C.), Sahlgrenska Academy at University of Gothenburg, SE-413 46 Gothenburg, Sweden; Laboratory of Molecular Endocrinology and Oncology (F.L.), Laval University Hospital Research Center (CRCHUL) and Laval University, Quebec, Canada G1V 4G2; Department of Medicine (Y.T.K.), Institute of Clinical Medicine, Helsinki University Central Hospital, 00290 Helsinki, Finland; ORTON Orthopedic Hospital of the Invalid Foundation (Y.T.K.), 00280 Helsinki, Finland; COXA Hospital for Joint Replacement, 33101 Tampere, Finland; and Department of Internal Medicine (C.O.), Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden

Address all correspondence and requests for reprints to: Helena Forsblad-d’Elia, Department of Rheumatology and Inflammation Research, Guldhedsgatan 10A, S-413 46 Göteborg, Sweden. E-mail: helena.forsblad{at}vgregion.se.

Context: 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.

Objective: 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.

Design: 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.

Results: Baseline erythrocyte sedimentation rate was inversely correlated with testosterone (Testo), dihydrotestosterone, and DHEA-S (r_s = –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 (r_s = –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.

Conclusions: 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.