title: Failure of oral DHEA treatment to increase local salivary androgen outputs of female patients with Sjögren's syndrome.
abstract: OBJECTIVE
  Sjögren's syndrome (SS) is a female-dominant autoimmune disease characterized by androgen depletion and defective dehydroepiandrosterone (DHEA) processing enzymatic machinery in the salivary glands. We hypothesized that, because of these local failures, DHEA replacement therapy would be unable to improve the local androgen deficiency in SS salivary glands.
  
  
  METHODS
  DHEA-deficient female SS patients (n = 12) were treated with placebo for 4 months followed by DHEA 50 mg q.d. for 4 months. Serum and saliva, collected in the morning before the trial and after both periods, were analysed for pro-hormones, androgens, and androgen metabolite using an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  DHEA treatment increased serum DHEA-sulfate from 1.3 ± 0.1 to 6.4 ± 1.3 µM (p = 0.005), DHEA from 16.5 ± 2.8 to 34.8 ± 8.2 nM (p = 0.012), androstenedione from 3.1 ± 0.3 to 17.2 ± 1.9 nM (p = 0.002), free testosterone from 2.2 ± 0.1 to 7.7 ± 1.1 pM (p = 0.002), DHT from 275.5 ± 24.4 to 834.6 ± 122.8 pM (p = 0.002) and 3-α-diol-G from 3.8 ± 0.6 to 13.6 ± 2.0 nM (p = 0.001). However, only salivary DHEA and DHT outputs increased significantly and 25% of the patients showed no increases, except for DHEA itself. Outputs of active androgens (T, DHT) and 3-α-diol-G metabolite correlated with salivation.
  
  
  CONCLUSIONS
  The local androgen deficiency in SS salivary glands is not only caused by low serum DHEA(-S) because restoration of systemic androgen levels by DHEA treatment did not correct local androgen depletion. This could be explained by low or no capacity of DHEA-substituted patients to convert the pro-steroid to active androgen metabolites. Such intracrine failures affect women in particular, who must produce their salivary T and DHT locally from DHEA.
authors: Department of Medicine, Hospital District of Helsinki and Uusimaa, Helsinki, Finland.
authors: P
authors: P
authors: Porola
authors: R H
authors: RH
authors: Straub
authors: L M
authors: LM
authors: Virkki
authors: Y T
authors: YT
authors: Konttinen
authors: D C
authors: DC
authors: Nordström
mesh_terms: D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood / Q000172:deficiency; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry; D012469:Salivary Glands / Q000187:drug effects*; D012859:Sjogren's Syndrome / Q000097:blood / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D000728:Androgens; D003687:Dehydroepiandrosterone