Objective: Because the secretion of dehydroepiandrosterone (DHEA), the exclusive source of sex steroids in postmenopausal women, is already decreased by 60% and continues to decline at the time of menopause, the objective of this study was to examine the effect of intravaginal DHEA on the symptoms and signs of vaginal atrophy.
Methods: This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone (DHEA) applied locally in the vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal women.
Results: All three doses (0.25%, 0.5%, and 1.0%) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the percentage of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks. At the standard 12-week time interval, 0.5% DHEA caused a 45.9 ± 5.31 (P < 0.0001 vs placebo) decrease in the percentage of parabasal cells, a 6.8 ± 1.29% (P < 0.0001) increase in superficial cells, a 1.3 ± 0.13 unit (P < 0.0001) decrease in vaginal pH, and a 1.5 ± 0.14 score unit (P < 0.0001) decrease in the severity of the most bothersome symptom. Similar changes were seen on vaginal secretions, color, epithelial surface thickness, and epithelial integrity. Comparable effects were observed at the 0.25% and 1.0% DHEA doses.
Conclusions: Local Prasterone, through local androgen and estrogen formation, causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids, which remain well within the normal postmenopausal range. This approach avoids the fear of systemic effects common to all presently available estrogen formulations and adds a novel physiological androgenic component to therapy.
This prospective, randomized, placebo-controlled study shows that local intravaginal application of low doses of dehydroepiandrosterone in postmenopausal women causes an improvement of the symptoms and signs of vaginal atrophy.
From the 1Laval University Hospital Research Center and Laval University, Quebec, Canada; 2Endoceutics Inc., Quebec City, QC, Canada; 3Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA; 4Clinique de Recherche en Santé des Femmes, Quebec City, Canada; 5Diex Recherche Inc., Sherbrooke, QC, Canada; 6Rapid Medical Research Inc., Cleveland, OH; 7Clinique Gynécologique, Shawinigan, Canada; 8Montreal Clinical Study Center, Montreal, Canada; 9Centre Hospitalier affilié Universitaire de Québec, Quebec City, Canada; 10McGill University Health Center, Royal Victoria Hospital, Montreal, QC, Canada; and 11Veristat Inc., Boston, MA.
Received November 10, 2008; revised and accepted January 26, 2009.
Funding/support: This study was sponsored by Endoceutics.
Financial disclosure/conflicts of interest: Dr. Labrie is President and CEO of Endoceutics. The other authors report no conflicts of interest, although the study was financed by Endoceutics. Patents for intravaginal Prasterone are the property of Endoceutics, Inc.
Address correspondence to: Fernand Labrie, MD, PhD, Endoceutics Inc., 2989 de la Promenade, Quebec City, QC, Canada G1W 2J5. E-mail: Fernand.Labrie@endoceutics.com