This study aims to confirm the local effects of intravaginal prasterone on moderate to severe dyspareunia, a symptom of vulvovaginal atrophy (VVA) associated with menopause.
In a prospective, randomized, double-blind, placebo-controlled phase III clinical trial, we examined the effects of daily intravaginal prasterone (6.5 mg) on four co–primary objectives, namely, percentage of vaginal parabasal cells, percentage of vaginal superficial cells, vaginal pH, and moderate to severe dyspareunia identified by women as the most bothersome VVA symptom.
After daily intravaginal prasterone administration for 12 weeks, the percentage of parabasal cells decreased by 45.8% compared with placebo (P < 0.0001), the percentage of superficial cells increased by 4.7% over placebo (P < 0.0001), and vaginal pH decreased by 0.83 pH units compared with placebo (P < 0.0001). The severity of most bothersome dyspareunia decreased by 46% over placebo (P = 0.013) at 12 weeks, whereas moderate to severe vaginal dryness decreased by 0.43 severity score units (or 42%) compared with placebo (P = 0.013). On gynecologic evaluation, a 14.4% to 21.1% improvement in vaginal secretions, epithelial integrity, epithelial surface thickness, and color over placebo (P = 0.0002 to P < 0.0001) was observed. Serum steroids, in agreement with the physiology of intracrinology and menopause, remained well within reference postmenopausal concentrations. All endometrial biopsies at 12 weeks have shown atrophy.
Daily intravaginal prasterone (0.50%; 6.5 mg) treatment has clinically and statistically significant beneficial effects on the four co–primary objectives of VVA, according to US Food and Drug Administration guidelines. No significant drug-related adverse effect in line with the strictly local action of treatment has been reported, thus providing a high benefit-to-risk ratio for intravaginal prasterone.
1Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA
2EndoCeutics Inc, Quebec City, QC, Canada
3Clinique de Recherche en Santé des Femmes, Quebec City, QC, Canada
4Columbus Center for Women's Health Research, Columbus, OH
5Medical Center for Clinical Research, San Diego, CA
6Veristat Inc, Holliston, MA.
Address correspondence to: Fernand Labrie, MD, PhD, EndoCeutics, Suite 500, 2975 Laurier Boulevard, Quebec City, Quebec, Canada G1 V 4M7. E-mail: Fernand.Labrie@endoceutics.com
Received 10 October, 2014
Revised 17 December, 2014
Accepted 17 December, 2014
Participating members of the VVA Prasterone Group: Aqua, Keith (Boyton Beach, FL); Archer, David F. (Norfolk, VA); Ayotte, Normand (Shawinigan, QC, Canada); Bachmann, Gloria (New Brunswick, NJ); Baron, Mira (Cleveland, OH); Beyer, Roger (Kalamazoo, MI); Blank, Steven (Sandy Spring, GA); Blouin, François (St-Romuald, QC, Canada); Bouchard, Céline (Quebec, QC, Canada); Cusan, Leonello (Quebec, QC, Canada); Giguère, Nicole (Drummondville, QC, Canada); Girard, Ginette (Sherbrooke, QC, Canada); Goldberg, Cynthia (Tucson, AZ); Goldstein, Irwin (San Diego, CA); Goldstein, Steven (New York, NY); Hauck, Brian (Calgary, AB, Canada); Kaunitz, Andrew (Jacksonville, FL); Khaled, Abdelmoula (Montreal, QC, Canada); Kirstein, Judith (West Jordan, UT); Koltun, William (San Diego, CA); Levine, Bruce (Moorestown, NJ); Lukes, Andrea (Durham, NC); Pinkerton, Joann (Charlottesville, VA); Portman, David J. (Columbus, OH); Swanson, Stephen (Lincoln, NE); Turner, Mark (Meridian, ID); Varano, Susann (Milford, CT); Wade, Anthony (Bathurst, NB, Canada); Waldbaum, Arthur (Denver, CO); Young, Douglas (Sacramento, CA).
Funding/support: This research was sponsored by EndoCeutics.
Financial disclosure/conflicts of interest: F.L. is president and chief executive officer of EndoCeutics. D.F.A. is a consultant to EndoCeutics and has received grants for clinical studies.