Vaginal Estrogen for Urinary tract infection prevention: A narrative review of evidence, guideliens, and regulatory gaps

Abstract

Background: Recurrent urinary tract infections (rUTIs) are common in peri- and postmenopausal women and impose substantial symptom, quality of life, and antimicrobial stewardship burdens, with particularly high incidence and hospitalization costs documented in England and UK primary care populations. Vaginal estrogen, by restoring urogenital epithelium and the lactobacillus-dominant microbiome, is recommended in several guidelines for preventing rUTI; including UK antimicrobial prescribing guidance for rUTIs and European Association of Urology recommendations. However, most formulations are licensed only for genitourinary syndrome of menopause, not for UTI prophylaxis. This creates a mismatch between the growing clinical evidence base and the absence of a specific regulatory indication for rUTI prevention across major regulatory agencies, including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which may contribute to underuse and clinician uncertainty. Objectives: To review and summarize the evidence on vaginal estrogen for prevention of recurrent urinary tract infections in peri- and postmenopausal women, with a particular focus on its use alone and in combination with antibiotic therapy, and on the gap between clinical guideline recommendations and regulatory product labelling. Methods: We conducted a structured narrative review focusing on randomized controlled trials and clinical practice guidelines that evaluate intravaginal estrogen for the prevention of rUTI in peri- and postmenopausal women. PubMed and Embase searches were performed using key terms for estrogen, urinary tract infection, and menopause, and were supplemented with targeted searches of major guidelines. Data were described in terms of study design, participant characteristics, estrogen formulations and dosing regimens, timing of initiation, comparators, outcome measures, and reported safety outcomes. Outcome: Evidence from five RCTs reported that low-dose vaginal estrogen, administered as creams, tablets, rings, or gels, reduced culture-confirmed rUTI episodes and improved vaginal health indices, with no head-to-head trials comparing estrogen formulations directly, precluding conclusions about the relative superiority of any single preparation, and a favorable local safety profile. One trial found estriol pessaries less effective than antibiotic prophylaxis for rUTI prevention, suggesting that estrogen alone may be insufficient in some women and that combined regimens warrant further investigation, although no trial has directly evaluated concurrent antibiotic and estrogen therapy. Initiation was predominantly prophylactic or post-antibiotic, and no identified trial evaluated co-initiation of vaginal estrogen with antibiotics at the onset of acute UTI, highlighting a persisting evidence gap regarding optimal timing of therapy. Conclusions and Outlook: Vaginal estrogen is an evidence-based yet underutilized strategy for rUTI prevention in peri- and postmenopausal women, supported by RCT data and guideline recommendations, but not recognized in current FDA-approved indications for vaginal estrogen products. Closing this evidence licensing gap will require regulatory reconsideration informed by existing trial data, alongside new pragmatic studies to refine timing, dosing, and formulation choices, to evaluate co-administration with antibiotics, and to refine timing, dosing, and formulation choices, and to evaluate the efficacy of combined estrogen and antibiotic co-administration; patient-centred research on women’s preferences, acceptability, and shared decision-making should follow once optimal therapeutic parameters have been established, as the nature of treatment will determine patient experience and response.