title: Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy.
abstract: OBJECTIVE
  While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness.
  
  
  METHODS
  Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo.
  
  
  RESULTS
  Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 μg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects.
  
  
  CONCLUSIONS
  The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.
authors.affiliation: * Clinique de Recherche en Santé des Femmes , Quebec City , Canada.
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.forename: F
authors.initials: F
authors.lastname: Labrie
authors.forename: D F
authors.initials: DF
authors.lastname: Archer
authors.forename: D J
authors.initials: DJ
authors.lastname: Portman
authors.forename: W
authors.initials: W
authors.lastname: Koltun
authors.forename: É
authors.initials: É
authors.lastname: Elfassi
authors.forename: D A
authors.initials: DA
authors.lastname: Grainger
authors.forename: N
authors.initials: N
authors.lastname: Ayotte
authors.forename: T A
authors.initials: TA
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Martens
authors.forename: A S
authors.initials: AS
authors.lastname: Waldbaum
authors.forename: C
authors.initials: C
authors.lastname: Labrie
authors.forename: I
authors.initials: I
authors.lastname: Côté
authors.forename: L
authors.initials: L
authors.lastname: Lavoie
authors.forename: C
authors.initials: C
authors.lastname: Martel
authors.forename: J
authors.initials: J
authors.lastname: Balser
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D001284:Atrophy / Q000150:complications / Q000188:drug therapy; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004414:Dyspareunia / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome; D014623:Vaginal Diseases / Q000150:complications / Q000188:drug therapy*; D014845:Vulvar Diseases / Q000150:complications / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D003687:Dehydroepiandrosterone
keywords: DHEA; LOW DOSING; VULVOVAGINAL ATROPHY