(017) At-Home Therapeutic Ultrasound Treatment for Vulvovaginal Atrophy (VVA): A Pilot Study

Abstract

Abstract Introduction VVA symptoms affect 50% of post-menopausal women and can be progressive without treatment. Hormonal therapies (HT) are the only FDA approved treatments for VVA, but many women prefer not to use or are not candidates for HT. As an alternative, an at-home therapeutic ultrasound system was developed to help women manage their VVA symptoms. Objective To evaluate the effectiveness and safety of therapeutic ultrasound compared with sham after 12 weeks of treatment for VVA. Methods This pilot study was a double-blind, multi-site, randomized, controlled trial (RCT) that assessed the effectiveness and safety of home-use therapeutic ultrasound applied to the vaginal introitus for 8 minutes/day on post-menopausal vaginal symptoms (Clinicaltrials.gov NCT04887701). Thirty-one women were screened between July 2021 and February 2022 at three sites, of which 26 (ages 54-65 yrs.) were randomized 1:1 to active treatment or sham. The intent-to-treat population included women with moderate to severe vaginal dryness and dyspareunia who were ≤15 yrs. postmenopausal. The primary outcome was change from baseline to week 12 in clinician-reported Vaginal Health Index (VHI) giving a numerical score (1-5) for each of the 5 parameters (tissue elasticity, vaginal fluid, pH, mucosa, and vaginal moisture). Women reported change in vaginal symptoms (dryness, soreness, irritation, and dyspareunia) measured by the Vaginal Assessment Scale (VAS), with a 4-level response score ranging from none (0), mild (1), moderate (2), to severe (3). VHI and VAS changes were assessed using mixed model analysis of variance. Women also rated their vaginal symptoms using the Patient Global Impression of Improvement (PGI-I) score with a 7-level response scale ranging from “very much better” (1) to “very much worse” (7). Results VHI increased with ultrasound treatment after the 12-week blinded period (least squares mean change ± SEM) 1.48 ± 0.77 (P=0.06) but less with sham 0.69 ± 0.75 (P=0.37). The empirical cumulative distribution functions for the change from baseline in the VHI score for the baseline severe population revealed that treatment showed a greater positive change in VHI at each percentile than sham (e.g., at the 50th percentile treatment had an improvement in VHI of 2.0 vs 0.0 for sham). Treatment also showed a greater negative change in VAS at each percentile than sham (e.g., at the 50th percentile treatment had an improved symptom reduction in VAS of -0.75 vs 0.0 for sham). The PGI-I showed more women experienced a clinically meaningful improvement to therapeutic ultrasound compared with sham (P=0.04). The ultrasound device was well tolerated without any safety signals. There were no differences in treatment-emergent adverse events between active treatment and sham and no serious adverse events. Conclusions This is the second pilot RCT to support a new and safe, non-HT treatment of VVA with therapeutic ultrasound. Improved vaginal dryness and dyspareunia scores are similar to pharmaceutical treatments (Bachmann 2010; Constantine 2017; Labrie 2016) but did not reach statistical significance due to the small sample size. These pilot RCTs, along with the open-label extension of this study, now form the basis for the anticipated FDA approved pivotal RCT. Disclosure Yes, this is sponsored by industry/sponsor: Madorra, Inc. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Madorra, Inc.