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).
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.
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.
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.
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.
Address correspondence to: Fernand Labrie, MD, PhD, EndoCeutics, 2975, Laurier Boulevard, Suite 500, Quebec City, QC G1V 4M7, Canada. E-mail: Fernand.Labrie@endoceutics.com
Received 18 March, 2015
Revised 1 October, 2015
Accepted 1 October, 2015
Funding/support: This research was sponsored by EndoCeutics.
Financial disclosure/conflicts of interest: DFA is a consultant to EndoCeutics and is a recipient of Grants for clinical studies. FL is President and CEO of EndoCeutics. DP reports consultancies: Sprout, Palatin, Nuelle, Actavis, Noven, Shionogi, Pfizer; past grant with TherapeuticsMD.