Vaginal Estrogen Application Techniques for Prevention of Urinary Tract Infection: A Randomized Trial.

Abstract

To determine whether periurethral estrogen application is noninferior to intravaginal estrogen application for the prevention of urinary tract infections (UTIs) in postmenopausal individuals with laboratory-proven recurrent UTI. The TAPER (Techniques of Applying Vaginal Estrogen for Prevention of Recurrent Urinary Tract Infections) trial was a single-center, nonblinded, randomized noninferiority trial that compared outcomes after a twice-weekly intravaginal estradiol applicator instillation of 1.0 g cream (intravaginal) compared with periurethral digital application of 0.5 g cream (periurethral) in postmenopausal individuals with recurrent UTIs. The primary outcome was the proportion of UTI-free participants at 6 months postintervention. Secondary outcomes included number of UTIs, the amount of time elapsed to the first UTI, vaginal pH, PGI-I (Patient Global Impression of Improvement) scores, patient experience with the study drug, study drug adverse effects, and urinary and sexual function. To achieve 80% power with a type 1 error of 5% and to account for loss to follow-up, 114 participants needed to be randomized based on a noninferiority margin of 25%. Of 270 eligible individuals, 114 consented and were randomized (57 intravaginal, 57 periurethral). Participants were predominantly White (92.1%) with a mean age of 71.1 years (range 52-93). Participants reported a median of three UTIs in the 12 months before enrollment. Individuals randomized to periurethral estrogen application had a similar proportion of UTI-free participants at 6 months as those randomized to intravaginal estrogen application (50.9% vs 52.6%; risk difference, -1.75 percentage points; 95% CI, -20.0 to 17.0 percentage points). Both groups experienced a decrease in vaginal pH at 6 months; the decreases did not differ by application method (-1.2 intravaginal vs -0.8 periurethral, P =.30). Participants assigned to intravaginal estrogen were more likely to experience vaginal itching after 3 months of use than those assigned to periurethral application (24.0% vs 2.4%, P <.01). Other outcomes did not differ by route of estrogen application. For postmenopausal individuals who are experiencing recurrent UTI, periurethral application of estradiol cream is noninferior to intravaginal application for UTI prevention. Both application methods resulted in approximately half of the participants being UTI-free at 6 months. ClinicalTrials.gov , NCT05472779.