Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.