A randomized, pilot trial comparing vaginal hyaluronic acid to vaginal estrogen for the treatment of genitourinary syndrome of menopause

Abstract

Objective: The aim of this study was to compare the efficacy of a non-hormone alternative, vaginal hyaluronic acid (HLA), to a standard-of-care therapy, vaginal estrogen, for the treatment of genitourinary syndrome of menopause (GSM).

Methods: This was a randomized, parallel arm pilot trial. Women with GSM were randomized to an HLA vaginal suppository or vaginal estrogen cream for 12 wk to compare the primary outcome, the vulvovaginal symptom questionnaire (VSQ) score. Secondary outcomes included the following: the female sexual function index (FSFI), the vaginal symptom index (VSI), visual analog scale (VAS) for dyspareunia, vaginal itching, and vaginal dryness, patient global impression of improvement (PGI-I) at follow-up, vaginal maturation index, and vaginal pH. Differences between treatment groups were estimated using the two-sided, two-sample t -test and 95% confidence intervals.

Results: Forty-nine women were randomized and 45 participants (vaginal estrogen = 23, vaginal HLA = 22) provided data at week 12. Baseline characteristics were similar in both groups. On the VSQ, there was no observed difference in overall scores between the HLA and vaginal estrogen groups at 12 wk ( P = 0.81). Improvement was seen within both treatment groups on the VSQ after 12 wk. The VAS score, total VSI score, total FSFI score, and vaginal pH improved over time; however, improvement did not differ between study arms. Over 90% participants noted improvement on the PGI-I in both groups ( P = 0.61). No treatment-related serious adverse events occurred.

Conclusions: There were no clinically meaningful differences between vaginal HLA and vaginal estrogen for the treatment of GSM after 12 wk. Vaginal HLA may be a promising non-hormone therapy for GSM.

Trial registration: ClinicalTrials.gov NCT04544475.

FIG. 1

Participant allocation.

FIG. 2

Patient global impression of improvement. Patient global impression of improvement scores 1 (very much better), 2 (much better), and 3 (slightly better) were reported as “better” and scores 4 (no change), 5 (slightly worse), 6 (much worse), and 7 (very much worse) were reported as “no change or worse”; ^aP value comparison of vaginal estrogen and vaginal hyaluronic acid (HLA) by Fisher's exact test; analysis sample size was vaginal estrogen = 23 participants and vaginal HLA = 22 participants.