Long-Term Adherence in a Randomized Controlled Clinical Trial Suggests Feasibility of a Novel Therapeutic Ultrasound Device to Treat Vulvovaginal Atrophy

Abstract Background A randomized (1:1), double-blind, sham-controlled study assessed effectiveness of home-use therapeutic ultrasound for vulvovaginal atrophy (VVA) in post-menopausal women. The objective of the present secondary analyses was to assess participant-reported compared to objectively-tracked adherence to the home-use therapy, and the association between treatment adherence and VVA improvement. Methods Participants applied ultrasound 8 min/day to the vaginal introitus for 12 weeks followed by open-label ultrasound treatment to week 48. In 42 post-menopausal women (ages 48–70) with self-assessed vaginal dryness and clinician-diagnosed VVA, self-reported treatment adherence was collected by daily electronic diary. Objective adherence was obtained from a device log recording date, time, and use duration. Clinicians scored vaginal tissue health using the Vaginal Health Index (VHI). Results At week 12, self-reported and device-log adherence rates (mean ± SD; Paired t-test) in the modified intent-to-treat population were high among those who remained in the study and were similar in both active treatment (n = 14) and sham (n = 15) groups. Active treatment self-reported adherence was 85.44% ± 20.07% and device-log adherence was 80.66% ± 26.89% (P = 0.6). Sham self-reported adherence was 89.82% ± 8.01% and device-log adherence was 82.53% ± 20.31% (P = 0.2). There was a significant, positive association between ultrasound treatment dose and improved VHI from baseline to week 12 (r = 0.510, P = 0.04; Pearson’s correlation). Thereafter, among participants who remained enrolled in the study, adherence (by device log) was not significantly different at week 24 or week 48 compared to the first 12 weeks (P = 0.5, ANOVA). Compared to baseline (Paired t-test), improvement in VHI was seen at week 24 (P = 0.03) and week 48 (P = 0.06). There were no differences in treatment-emergent adverse events (AEs) between ultrasound treatment versus sham. Participants liked that the ultrasound therapy was non-invasive (37%); easy to use (26%); less messy than typical treatments (16%); able to make the participant feel healthier (10%); and was able to generate tissue moisture (11%). Conclusions Participant-reported adherence was not statistically different than objectively tracked adherence. Both measures of adherence were high among those who remained in the study, and such adherence to daily, at-home ultrasound therapy proved efficacious in improving VVA. Trial registration Clinicaltrials.gov NCT03931213. 24/04/2019, https://clinicaltrials.gov/study/NCT03931213?id=NCT03931213&rank=1&tab=history&a=2