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

Abstract

Highlights What are the main findings? Both active interventions were associated with short-term within-group improvements in VSQ and FSFI scores; without a sham or untreated control, these changes cannot establish intervention-specific efficacy. The primary between-group comparison showed no difference in total VSQ change, whereas the exploratory baseline-adjusted total FSFI estimate favored Er:YAG laser therapy; domain-level analyses were exploratory and were not adjusted for multiplicity. What are the implications of the main findings? These preliminary comparative findings support further controlled evaluation of non-hormonal strategies for managing genitourinary syndrome of menopause in cancer survivors for whom hormonal therapy may be contraindicated or avoided. Routine assessment and treatment of vulvovaginal symptoms and sexual dysfunction should be integrated into comprehensive survivorship care for women with hormone-dependent malignancies. 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.