A Controlled Trial of Intravaginal Estriol in Postmenopausal Women with Recurrent Urinary Tract Infections

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Abstract

Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections. We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up. The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment. The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.

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J P Davick, Truman Young, Randall K. Holmes … (1989)

A predominance of Lactobacillus species in the vaginal flora is considered normal. In women with bacterial vaginosis, the prevalence and concentrations of intravaginal Gardnerella vaginalis and anaerobes are increased, whereas the prevalence of intravaginal Lactobacillus species is decreased. Because some lactobacilli are known to produce hydrogen peroxide (H2O2), which can be toxic to organisms that produce little or no H2O2-scavenging enzymes (e.g., catalase), we postulated that an absence of H2O2-producing Lactobacillus species could allow an overgrowth of catalase-negative organisms, such as those found among women with bacterial vaginosis. In this study, H2O2-producing facultative Lactobacillus species were found in the vaginas of 27 (96%) of 28 normal women and 4 (6%) of 67 women with bacterial vaginosis (P less than 0.001). Anaerobic Lactobacillus species (which do not produce hydrogen peroxide) were isolated from 24 (36%) of 67 women with bacterial vaginosis and 1 (4%) of 28 normal women (P less than 0.001). The production of H2O2 by Lactobacillus species may represent a nonspecific antimicrobial defense mechanism of the normal vaginal ecosystem.

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D Eschenbach, S J Klebanoff, Susan L. Hillier … (1991)

H2O2-generating lactobacilli (LB+) are present in the vagina of most normal women but are absent from most women with bacterial vaginosis (BV). LB+ at high concentration was toxic to Gardnerella vaginalis (the predominant organism in the vagina of women with BV); when the LB+ was lowered to a level where it was ineffective alone, the addition of myeloperoxidase and chloride reinstituted toxicity. Toxicity was inhibited by catalase and was not seen when H2O2-negative lactobacilli were used, implicating H2O2 as the toxic molecule. LB+ could be replaced by H2O2 and chloride by iodide, bromide, or thiocyanate. The optimum pH for inhibition of G. vaginalis was 5.0-6.0 LB+ also was autoinhibitory when combined with myeloperoxidase and chloride. LB+ alone at low concentrations was toxic to Bacteroides bivius through the formation of H2O2. Adequate amounts of peroxidase were found in the vagina of 17 of 21 women. These findings suggest that LB+ may contribute to the control of the vaginal flora, particularly in the presence of peroxidase and a halide.

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Association between bacterial vaginosis and acute cystitis in women using diaphragms.

Kevin C. Johnson, S Fihn, Steven Hooton … (1989)

We hypothesized that the increased vaginal fluid pH and altered vaginal microflora characteristic of bacterial vaginosis might predispose young women to introital colonization with Escherichia coli and to acute cystitis. To evaluate this hypothesis, we studied 291 women who presented with acute urinary symptoms for association of clinically defined bacterial vaginosis and vaginal conditions associated with this syndrome (increased vaginal fluid pH, absence of lactobacilli, and abnormal vaginal fluid gas-liquid chromatographic patterns) with E coli introital colonization and urinary tract infection. Escherichia coli introital colonization and urinary tract infection were both significantly more frequent among women with a high vaginal fluid pH, an absence of vaginal lactobacilli, or an abnormal vaginal fluid gas-liquid chromatographic pattern characteristic of bacterial vaginosis. Escherichia coli introital colonization was also more frequent in women with bacterial vaginosis. These associations and an association of bacterial vaginosis and E coli urinary tract infection were strong only among the 144 women who were diaphragm users. We conclude that bacterial vaginosis, or an altered vaginal microflora as reflected by an abnormal gas-liquid chromatographic pattern characteristic of bacterial vaginosis, is associated with E coli introital colonization and acute symptomatic urinary tract infection in women who use diaphragms.