A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women

OBJECTIVE: The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring (Estring; Pharmacia & Upjohn, Inc, Uppsala, Sweden) compared with no estrogen treatment. The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms. The study also sought to detect a difference in decrease of vaginal pH to <5.5 and to record adverse events. STUDY DESIGN: This was a multicenter, randomized, open, parallel-group study with an untreated control group. Postmenopausal women with recurrent symptomatic, bacteriologically confirmed urinary tract infections were randomly assigned to receive either Estring (2 mg estradiol) or no estrogen treatment. One ring was carried vaginally for 12 weeks. The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group. Both intent-to-treat and per-protocol analyses were performed to evaluate efficacy, whereas the safety analysis was limited to the intent-to-treat group. The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function. To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence. RESULTS: A total of 108 women were randomly assigned, 53 to the Estring group and 55 to the control group. The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group (P=.008). After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45% in the women with the vaginal ring compared with approximately 20% in the control group. Estring lowered vaginal pH, and the time to first recurrence was effectively prolonged by Estring treatment. Vaginal and, to a lesser extent, urethral mucosal cells were significantly more mature in the Estring group. No unexpected adverse events were found. CONCLUSION: Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year. The silicone vaginal ring also has a clinically significant ability to alleviate other postmenopausal urogenital symptoms. Estring is safe and well tolerated.