Does age at the start of treatment for vaginal atrophy predict response to vaginal estrogen therapy? Post hoc analysis of data from a randomized clinical trial involving 205 women treated with 10 μg estradiol vaginal tablets

Abstract

Objective: Local estrogen therapy (ET) can improve vaginal atrophy symptoms and associated cellular changes in postmenopausal women. This study evaluated whether age at the start of treatment influences response.

Methods: This post hoc analysis used data from a double-blind, randomized, placebo-controlled trial (NCT00108849), which treated 205 postmenopausal women aged ≥45 years with 10 μg vaginal ET for 52 weeks.Women aged <60 or ≥60 years at treatment start were evaluated according to the following: vaginal maturation index (assessed by vaginal cytology samples), vaginal pH, and most bothersome symptom (both graded on four-point scales). Covariance analysis aimed to evaluate mean change differences between groups from baseline-week 52.

Results: Vaginal ET improved vaginal maturation index (for all cell layers), vaginal pH, and symptom scores for both age groups. However, cytological profiles were significantly different in the <60 (n = 143) versus ≥60 years group (n = 55, estimated effect: -3.7, P = 0.0003 [parabasal cells]; 5.8, P = 0.0002 [intermediate cells]), indicating reduced cellular responsiveness to treatment among older women. Treatment effect on vaginal pH was less for older women, with a between-group difference of -0.19 (standard error = 0.05; P = 0.0003).

Conclusions: Findings suggest that treatment may be initiated at any age since low-dose vaginal ET improved symptoms and signs of vaginal atrophy in both younger (<60 years) and older (≥60 y) women. The stronger response observed in younger women supports current clinical recommendations to start treatment early. Continued treatment may be important to avoid recurrence of vaginal atrophy.