title: Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women.
abstract: OBJECTIVE
  This study aims to evaluate the effects of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women.
  
  
  METHODS
  Intravaginal DHEA (6.5 mg) was administered daily for 52 weeks to 422 women who had endometrial biopsy at baseline and end of study, whereas 15 women were similarly treated for 26 to 52 weeks. Participants in three other studies received 3.25 mg (n = 126), 6.5 mg (n = 129), or 13 mg (n = 30) of DHEA for 12 weeks; women similarly had baseline and end-of-study biopsies. Endometrial biopsy samples were available for 668 women at baseline and end of study, with sufficient material for analysis.
  
  
  RESULTS
  Endometrial atrophy or inactive endometrium (668 women) was found in all women treated with intravaginal DHEA. Similar atrophy was observed in 119 of 121 participants with sufficient material for analysis who received placebo.
  
  
  CONCLUSIONS
  After cessation of estradiol secretion by the ovaries at menopause, the estrogens made by mechanisms of intracrinology are inactivated intracellularly at their site of formation and action, thus maintaining serum estradiol at biologically inactive concentrations to avoid stimulation of the endometrium. The absence of enzymes that are able to transform DHEA into estrogens in the endometrium explains the typical endometrial atrophy in all normal postmenopausal women in the presence of variable concentrations of circulating endogenous DHEA. According to these mechanisms, the inactive sex steroid precursor DHEA administered intravaginally acts exclusively in the vagina, whereas all serum sex steroids remain well within the biologically inactive postmenopausal reference range, thus avoiding any stimulation of the already atrophic endometrium.
authors.affiliation: 1Columbus Center for Women's Health Research, Columbus, OH 2EndoCeutics Inc, Quebec City, QC, Canada 3CONRAD Clinical Research Center, Norfolk, VA 4Clinique de Recherche en Santé des Femmes, Quebec City, QC, Canada 5Clinique de Recherche en Traitements Hormonaux, Quebec City, QC, Canada 6Diex Recherche Montréal Inc, Montreal, QC, Canada 7Clinique de Gynécologie, Shawinigan, QC, Canada 8Medical Center for Clinical Research, San Diego, CA 9Pro-Recherche, St-Romuald, QC, Canada 10Northern Califonia Research, Sacramento, CA 11Maritime Research Center, Bathurst, NB, Canada 12Centre Hospitalier Universitaire de Quebec, Quebec City, QC, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Portman
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: Céline
authors.initials: C
authors.lastname: Bouchard
authors.forename: Leonello
authors.initials: L
authors.lastname: Cusan
authors.forename: Ginette
authors.initials: G
authors.lastname: Girard
authors.forename: Normand
authors.initials: N
authors.lastname: Ayotte
authors.forename: William
authors.initials: W
authors.lastname: Koltun
authors.forename: François
authors.initials: F
authors.lastname: Blouin
authors.forename: Douglas
authors.initials: D
authors.lastname: Young
authors.forename: Anthony
authors.initials: A
authors.lastname: Wade
authors.forename: Céline
authors.initials: C
authors.lastname: Martel
authors.forename: Robert
authors.initials: R
authors.lastname: Dubé
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D001284:Atrophy; D001706:Biopsy; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000009:adverse effects; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause / Q000502:physiology*; D014621:Vagina / Q000473:pathology; D014844:Vulva / Q000473:pathology
chemical_list: D010919:Placebos; D003687:Dehydroepiandrosterone