title: Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women.
abstract: The primary objective of this study was measurement of the systemic bioavailability of DHEA and its metabolites following daily intravaginal application of the sex steroid precursor. Forty postmenopausal women were randomized to receive a daily dose of one ovule of the following DHEA concentrations: 0.0%, 0.5%, 1.0% or 1.8%. After only 7 days of treatment, the maturation value of the vaginal epithelial cells was significantly increased while the vaginal pH was significantly decreased at all DHEA doses. These important local effects were observed while the serum concentrations of estradiol and testosterone remained within the values found in normal postmenopausal women at all DHEA doses. Similar observations were made for serum androstenedione, estrone, estrone-sulfate and DHEA-sulfate. Even at the highest 1.8% DHEA dose, serum DHEA was increased at the levels found in normal premenopausal women. The present data show that the intravaginal administration of DHEA permits to rapidly achieve the local beneficial effects against vaginal atrophy without significant changes in serum estrogens, thus avoiding the increased risk of breast cancer associated with the current intravaginal or systemic estrogenic formulations. In addition, the recent observation that DHEA is transformed into both androgens and estrogens in the vagina permits to exert benefits on all the three layers of the vaginal wall.
authors.affiliation: Oncology and Molecular Endocrinology Research Center, Laval University Hospital Research Center (CRCHUL) and Laval University, 2705 Laurier Boulevard, Quebec City, Quebec G1V 4G2, Canada. Fernand.Labrie@crchul.ulaval.ca
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: Leonello
authors.initials: L
authors.lastname: Cusan
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gomez
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côté
authors.forename: René
authors.initials: R
authors.lastname: Bérubé
authors.forename: Patrick
authors.initials: P
authors.lastname: Bélanger
authors.forename: Céline
authors.initials: C
authors.lastname: Martel
authors.forename: Claude
authors.initials: C
authors.lastname: Labrie
mesh_terms: D019540:Area Under Curve; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause / Q000378:metabolism*; D014621:Vagina / Q000166:cytology / Q000187:drug effects* / Q000473:pathology
chemical_list: D010919:Placebos; D003687:Dehydroepiandrosterone