Recurrent urinary tract infections (rUTI) are a significant health concern among women, affecting
quality of life and resulting in substantial healthcare burden. Among postmenopausal women, the
incidence of rUTI is particularly high, due to physiological changes, including estrogen deficiency,
which can lead to alterations in the microbiomes, pH changes, cellular architecture and coaptation, all
of which contribute to vulnerability. Vaginal estrogen reduces UTI recurrence; however, data on its
effect in mitigating serious adverse outcomes—such as sepsis and mortality are only just emerging.
The primary goal of this study was to demonstrate rates of serious adverse outcomes in
postmenopausal women with rUTI in the presence and absence of vaginal estrogen.

IRB approval was obtained. Epic Cosmos data (a cloud-based research platform developed by Epic
that aggregates de-identified patient records from Epic EHR systems across multiple healthcare
organizations) was used to query 3 year data on 11,054,906 female patients with recurrent UTI using
versus not using vaginal estrogen along the following adverse outcomes: sepsis, hospital admission,
and mortality. Chi-square tests were employed to determine the differences in outcomes.

In postmenopausal individuals with rUTI, vaginal estrogen use was significantly associated with reduced adverse outcomes. The incidence of sepsis was markedly lower in the estrogen group (10.6% vs. 19.4%, OR = 0.49, 95% CI: 0.49–0.50), indicating a 51% reduction in sepsis risk. Vaginal estrogen use was also associated with a 22% lower likelihood of hospitalization (OR = 0.78, 95% CI: 0.76–0.80). Mortality was significantly reduced among estrogen users (0.42% vs. 1.54%, OR = 0.27, 95% CI: 0.25–0.29), corresponding to a 73% reduction in the odds of death. In contrast, no significant association between vaginal estrogen use and adverse outcomes was observed among premenopausal women with rUTI, with hospitalization rates showing only a minimal difference between groups.

Women greater than 55 years old with recurrent UTI’s who are on vaginal estrogen experience
significantly lower rates of hospitalization, sepsis, and mortality

Vaginal estrogen use in postmenopausal women with rUTI is associated with a 51% reduction in sepsis, 73% reduction in mortality, and 22% lower hospitalization rates. These benefits were not observed in premenopausal women, highlighting a postmenopausal-specific protective effect. Given the significant clinical and economic burden of rUTI-related complications, vaginal estrogen may serve as a cost-effective strategy to improve patient outcomes. Further research is warranted to support its broader adoption as a standard preventive measure in postmenopausal individuals with rUTI.