Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy.

OBJECTIVE: The aim of this study was to evaluate low-dose synthetic conjugated estrogens A (SCE-A) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy (VVA) in a symptomatic postmenopausal population. METHODS: In a multicenter, double-blind, randomized, placebo-controlled study, 305 women with symptoms of VVA were treated with either 1 g SCE-A cream (n = 150) or matching placebo (n = 155) for a period of up to 12 weeks. Participants had to have a vaginal pH of greater than 5, less than or equal to 5% superficial cells on a vaginal smear, and at least one of five symptoms of VVA (dryness, soreness, irritation, pain with intercourse, and bleeding after intercourse) that was moderate or severe in intensity. Women had to select one moderate or severe symptom as the most bothersome. RESULTS: Efficacy was assessed at 2, 3, 4, 8, and 12 weeks and included the change from baseline in the severity of the most bothersome symptom (MBS), maturation index, and pH. Most women identified vaginal dryness as the MBS (48%) followed by pain with intercourse (31.3%). A statistically significant increase in the maturation index and significant decreases in pH and severity of the MBS were observed for those treated with SCE-A vaginal cream compared with placebo. CONCLUSIONS: A low dose (1 g = 0.625 mg) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three coprimary efficacy measures of maturation index, pH, and severity of the MBS.

Measuring symptom relief in studies of vaginal and vulvar atrophy: the most bothersome symptom approach.

OBJECTIVE: To assess the importance and usefulness of self-reported symptom data, especially the most bothersome symptom, in the evaluation of treatment for vulvovaginal atrophy. DESIGN: This was a double-blind, placebo-controlled multicenter study. Women rated symptoms associated with vaginal atrophy (vaginal dryness, vaginal/vulvar irritation/itching, vaginal/vulvar soreness, and dyspareunia) before and during treatment and selected one moderate to severe symptom as the most bothersome. RESULTS: Among 310 women (n = 156 placebo), vaginal dryness and dyspareunia were most commonly classified as moderate to severe and as most bothersome (44.4% and 30.2%, respectively). For both symptoms, the effect size favoring active treatment consistently increased as the cohort was more narrowly defined (all treated women, women who classified the symptom as moderate or severe, and those who classified the symptom as most bothersome). Compared with the standardized effect sizes for all women, those calculated from the most bothersome symptom were 49% and 62% greater for dyspareunia and dryness, respectively. CONCLUSION: : The most bothersome symptom approach represents a meaningful new standard for measurement of self-assessed vulvovaginal atrophy symptom change, but evaluation of change in individual symptoms remains an important, unbiased primary analysis of efficacy in vulvovaginal atrophy studies.