title: Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.
abstract: OBJECTIVE
  The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM).
  
  
  METHODS
  In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively.
  
  
  RESULTS
  After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6% of the participants.
  
  
  CONCLUSIONS
  The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.
authors.affiliation: 1EndoCeutics Inc, Quebec City, Quebec, Canada 2CONRAD Clinical Research Center, Norfolk, VA 3Medical Center for Clinical Research, San Diego, CA 4Clinique Médicale St-Louis (recherche) Inc, Quebec City, Quebec, Canada 5Northern California Research, Sacramento, CA 6Q&T Recherche Sherbrooke, Sherbrooke, Quebec, Canada 7Columbus Center for Women's Health Research, Columbus, OH 8Veristat, Holliston, MA 9StatLog Consulting Inc, Ottawa, Ontario, Canada.
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: William
authors.initials: W
authors.lastname: Koltun
authors.forename: Andrée
authors.initials: A
authors.lastname: Vachon
authors.forename: Douglas
authors.initials: D
authors.lastname: Young
authors.forename: Louise
authors.initials: L
authors.lastname: Frenette
authors.forename: David
authors.initials: D
authors.lastname: Portman
authors.forename: Marlene
authors.initials: M
authors.lastname: Montesino
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côté
authors.forename: Julie
authors.initials: J
authors.lastname: Parent
authors.forename: Lyne
authors.initials: L
authors.lastname: Lavoie
authors.forename: Adam
authors.initials: A
authors.lastname: Beauregard
authors.forename: Céline
authors.initials: C
authors.lastname: Martel
authors.forename: Mario
authors.initials: M
authors.lastname: Vaillancourt
authors.forename: John
authors.initials: J
authors.lastname: Balser
authors.forename: Érick
authors.initials: É
authors.lastname: Moyneur
mesh_terms: D000282:Administration, Intravaginal; D000368:Aged; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D004311:Double-Blind Method; D004414:Dyspareunia / Q000188:drug therapy*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D017698:Postmenopause; D013577:Syndrome; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy*; D014844:Vulva / Q000187:drug effects* / Q000473:pathology; D014845:Vulvar Diseases / Q000188:drug therapy* / Q000473:pathology
chemical_list: D003687:Dehydroepiandrosterone