title: Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.
abstract: OBJECTIVE
  Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day).
  
  
  METHODS
  A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100).
  
  
  RESULTS
  In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P < 0.001), but with negligible differences between these 2 treatments. The mean between-treatment difference was -0.1 for general fatigue (the primary outcome measure), 0.0 for physical fatigue, 0.0 for mental fatigue, 0.0 for reduced motivation, 0.3 for reduced activity, and 2.2 for the fatigue VAS. None of these differences was statistically significant.
  
  
  CONCLUSIONS
  Similar to earlier results using pharmacologic doses, substitution treatment with 50 mg of DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Liisa M
authors.initials: LM
authors.lastname: Virkki
authors.forename: Pauliina
authors.initials: P
authors.lastname: Porola
authors.forename: Helena
authors.initials: H
authors.lastname: Forsblad-d'Elia
authors.forename: Sigridur
authors.initials: S
authors.lastname: Valtysdottir
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Solovieva
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use*; D005221:Fatigue / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D003687:Dehydroepiandrosterone