Assessing vaginal health and treatment response in women with hormone-dependent malignancies: a comparative analysis of clinical, cytological, and histological assessment methods

Genitourinary syndrome of menopause (GSM) is common among women with hormone-dependent malignancies and often requires non-hormonal management. Clinical, cytological, and histological measures assess different aspects of vaginal health, but their relationships and responsiveness to treatment remain unclear. This study compared these assessment methods in women undergoing non-hormonal treatment for GSM. This post hoc secondary analysis of a prospective randomized pilot study included 65 women with hormone-dependent breast or endometrial cancer and symptomatic GSM. Participants received either non-ablative Er: YAG vaginal laser therapy or a vaginal gel containing 0.2% hyaluronic acid. Vaginal Health Index (VHI) and Vaginal Maturation Index (VMI) data were available for all 65 participants. Histological data were available for 64 participants at baseline and 63 at follow-up, providing 63 complete pairs. Assessments were performed at baseline and one month after treatment completion. Relationships between measures were evaluated using Spearman correlations. Responsiveness was quantified using effect size r derived from Wilcoxon signed-rank tests. Exploratory univariable linear regression examined associations between changes in clinical or cytological measures and histological outcomes. At baseline, VMI correlated positively with VHI (ρ = 0.498, p < 0.001), epithelial thickness (ρ = 0.466, p < 0.001), and glycogenization (ρ = 0.385, p = 0.002), and negatively with inflammatory infiltration (ρ = −0.436, p < 0.001). VHI showed weaker nominal associations with glycogenization (ρ = 0.267, p = 0.033) and inflammatory infiltration (ρ = −0.261, p = 0.036). Changes in VMI and VHI were not significantly correlated. In pooled analyses, VHI showed the greatest statistical responsiveness ( r = 0.87), whereas VMI showed negligible responsiveness ( r = 0.00). Responsiveness was moderate for epithelial thickness ( r = 0.37) and large for capillary density ( r = 0.50) and elastin fiber density ( r = 0.76). Exploratory regression analyses identified no significant associations between changes in VHI or VMI and histological outcomes. Clinical, cytological, and histological measures showed limited observed overlap and may provide complementary information. VMI primarily reflected baseline epithelial status, VHI showed the greatest short-term statistical responsiveness, and histology captured tissue-level changes. Outcome selection in future studies should therefore reflect the specific clinical or research objective. ClinicalTrials.gov NCT07420647; retrospectively registered, first posted on 19 February 2026.