An ultra-low dose (10μg) estradiol vaginal tablet improves signs and symptoms associated with vaginal atrophy

Abstract

OBJECTIVE: To assess the efficacy of a 10μg 17β-estradiol (E2) vaginal tablet for the treatment of vaginal atrophy in postmenopausal women.DESIGN: This was a 52-week, randomized, double-blind, multicenter, placebo-controlled study. Subjects were randomized 2:1 to receive either a 10μg E2 or a placebo tablet administered vaginally once-daily for the first two weeks of the study and then twice-weekly thereafter. Subjects enrolled in this study (N=309) were non-hysterectomized postmenopausal women ≥45 years of age, ≥2 years after last menses or bilateral oophorectomy, with ≥3 urogenital symptoms (≥1 moderate to severe), ≤5% superficial cells, vaginal pH>5 and endometrial thickness <4mm.MATERIALS AND METHODS: Primary efficacy assessments included most bothersome urogenital symptoms, vaginal pH, vaginal cytology and epithelial maturation reported using the Maturation Index [MI] and Value [MV]. At each visit, subjects completed a self-administered questionnaire describing symptoms associated with vaginal atrophy (vaginal dryness, irritation/itching, soreness, dysuria, dyspareunia and bleeding during sexual activity) and symptom severity (coded as not applicable, none=0, mild=1, moderate=2, severe=3). An ANCOVA model was used for between-treatment efficacy comparisons.RESULTS: At baseline, of the 6 most bothersome urogenital symptoms associated with vaginal atrophy, dyspareunia (placebo, 60.8%; E2, 52.5%), vaginal dryness (placebo, 26.5%; E2, 28.4%), and irritation/itching (placebo, 9.8%; E2, 12.3%) were reported by the largest proportions of subjects. At week 12, the changes from baseline in mean score of most bothersome symptom for placebo and E2, respectively, were −0.90 and −1.22 for dyspareunia, −0.85 and −1.22 for vaginal dryness, and −0.80 and −1.20 for irritation/itching. An analysis of the change from baseline in mean composite most bothersome symptom scores showed that vaginal E2 provided significant improvements compared with placebo at week 12 (LOCF, p=0.003), week 8 (p=0.014) and week 52 (LOCF, p=0.004). Significant improvements from baseline with vaginal E2 were demonstrated for MI, MV and vaginal pH at all assessed timepoints compared with placebo (p<0.001).CONCLUSIONS: An ultra-low dose 10μg 17β-estradiol vaginal tablet improves vaginal maturation and provides relief from most bothersome urogenital symptoms associated with estrogen deficiency-induced vaginal atrophy. OBJECTIVE: To assess the efficacy of a 10μg 17β-estradiol (E2) vaginal tablet for the treatment of vaginal atrophy in postmenopausal women. DESIGN: This was a 52-week, randomized, double-blind, multicenter, placebo-controlled study. Subjects were randomized 2:1 to receive either a 10μg E2 or a placebo tablet administered vaginally once-daily for the first two weeks of the study and then twice-weekly thereafter. Subjects enrolled in this study (N=309) were non-hysterectomized postmenopausal women ≥45 years of age, ≥2 years after last menses or bilateral oophorectomy, with ≥3 urogenital symptoms (≥1 moderate to severe), ≤5% superficial cells, vaginal pH>5 and endometrial thickness <4mm. MATERIALS AND METHODS: Primary efficacy assessments included most bothersome urogenital symptoms, vaginal pH, vaginal cytology and epithelial maturation reported using the Maturation Index [MI] and Value [MV]. At each visit, subjects completed a self-administered questionnaire describing symptoms associated with vaginal atrophy (vaginal dryness, irritation/itching, soreness, dysuria, dyspareunia and bleeding during sexual activity) and symptom severity (coded as not applicable, none=0, mild=1, moderate=2, severe=3). An ANCOVA model was used for between-treatment efficacy comparisons. RESULTS: At baseline, of the 6 most bothersome urogenital symptoms associated with vaginal atrophy, dyspareunia (placebo, 60.8%; E2, 52.5%), vaginal dryness (placebo, 26.5%; E2, 28.4%), and irritation/itching (placebo, 9.8%; E2, 12.3%) were reported by the largest proportions of subjects. At week 12, the changes from baseline in mean score of most bothersome symptom for placebo and E2, respectively, were −0.90 and −1.22 for dyspareunia, −0.85 and −1.22 for vaginal dryness, and −0.80 and −1.20 for irritation/itching. An analysis of the change from baseline in mean composite most bothersome symptom scores showed that vaginal E2 provided significant improvements compared with placebo at week 12 (LOCF, p=0.003), week 8 (p=0.014) and week 52 (LOCF, p=0.004). Significant improvements from baseline with vaginal E2 were demonstrated for MI, MV and vaginal pH at all assessed timepoints compared with placebo (p<0.001). CONCLUSIONS: An ultra-low dose 10μg 17β-estradiol vaginal tablet improves vaginal maturation and provides relief from most bothersome urogenital symptoms associated with estrogen deficiency-induced vaginal atrophy.