Patient-Reported Outcomes Following Non-Hormonal Treatment of Genitourinary Syndrome of Menopause in Women with Hormone-Dependent Cancer: A Prospective Randomized Pilot Study

Abstract

Background: Genitourinary syndrome of menopause (GSM) is a common consequence of hypoestrogenism that negatively affects vulvovaginal health, sexual function, and quality of life. Evidence comparing non-hormonal treatment options in women with hormone-dependent malignancies remains limited. This study evaluated patient-reported outcomes following non-ablative Er:YAG laser therapy or hyaluronic acid vaginal gel in women with hormone-dependent cancer and GSM. Methods: In this prospective randomized pilot study, 65 women with hormone-dependent malignancies and GSM were randomized to receive either three sessions of non-ablative Er:YAG vaginal laser therapy (n = 34) or 0.2% hyaluronic acid vaginal gel applied intravaginally every 72 h for two months (n = 31). The primary outcome was change in the total Vulvovaginal Symptom Questionnaire (VSQ) score; change in the total Female Sexual Function Index (FSFI) score was a secondary outcome, and domain-level analyses were exploratory. Outcomes were assessed at baseline and one month after treatment. Wilcoxon signed-rank and Mann–Whitney U tests were used for the principal analyses; adjusted analyses were performed using ANCOVA. The study was retrospectively registered at ClinicalTrials.gov (Identifier: NCT07420647; first posted on 19 February 2026). Results: Within-group improvements were observed under both active interventions. The primary between-group comparison showed no difference in total VSQ change (p = 0.398). Total FSFI change favored laser therapy in the unadjusted between-group comparison (p = 0.034), and the exploratory baseline-adjusted difference was 2.72 points (95% CI, 0.19–5.25; p = 0.036). Domain-level analyses were exploratory and were not adjusted for multiplicity. Conclusions: In this active-comparator pilot study, total VSQ change was comparable between groups and the adjusted total FSFI estimate favored laser therapy. Without a sham or untreated control, within-group changes cannot establish intervention-specific efficacy; these comparative findings require confirmation in larger controlled trials.