Urinary microbiome community types associated with urinary incontinence severity in women.

BACKGROUND: Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity. OBJECTIVE: This study aimed to test whether specific urinary or vaginal microbiome community types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence. STUDY DESIGN: This planned secondary, cross-sectional analysis evaluated associations between the urinary and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and Urinary Distress Inventory questionnaires collected at baseline. Catheterized urine samples and vaginal swabs were concurrently collected before treatment at baseline to assess the urinary and vaginal microbiomes. Of note, 16S rRNA V4 to V6 variable regions were sequenced, characterizing bacterial taxa to the genus level using the DADA2 pipeline and SILVA database. Using Dirichlet multinomial mixtures methods, samples were clustered into community types based on core taxa. Associations between community types and severity measures (Urinary Distress Inventory total scores, Urinary Distress Inventory subscale scores, and the number of urinary incontinence episodes [total, urgency, and stress] from the bladder diary) were evaluated using linear regression models adjusted for age and body mass index. In addition, alpha diversity measures for richness (total taxa numbers) and evenness (proportional distribution of taxa abundance) were analyzed for associations with urinary incontinence episodes and community type. RESULTS: Overall, 6 urinary microbiome community types were identified, characterized by varying levels of common genera (Lactobacillus, Gardnerella, Prevotella, Tepidimonas, Acidovorax, Escherichia, and others). The analysis of urinary incontinence severity in 126 participants with mixed urinary incontinence identified a Lactobacillus-dominated reference group with the highest abundance of Lactobacillus (mean relative abundance of 76%). A community characterized by fewer Lactobacilli (mean relative abundance of 19%) and greater alpha diversity was associated with higher total urinary incontinence episodes (2.67 daily leaks; 95% confidence interval, 0.76-4.59; P=.007) and urgency urinary incontinence episodes (1.75 daily leaks; 95% confidence interval, 0.24-3.27; P=.02) than the reference group. No significant association was observed between community type and stress urinary incontinence episodes or Urogenital Distress Inventory total or subscores. The composition of vaginal community types and urinary community types were similar but composed of slightly different bacterial taxa. Vaginal community types were not associated with urinary incontinence severity, as measured by bladder diary or Urogenital Distress Inventory total and subscale scores. Alpha diversity indicated that greater sample richness was associated with more incontinence episodes (observed genera P=.01) in urine. Measures of evenness (Shannon and Pielou) were not associated with incontinence severity in the urinary or vaginal microbiomes. CONCLUSION: In the urobiome of women with mixed urinary incontinence, a community type with fewer Lactobacilli and more diverse bacteria was associated with more severe urinary incontinence episodes (total and urgency) compared with a community type with high predominance of a single genus, Lactobacillus. Whether mixed urinary incontinence severity is due to lesser predominance of Lactobacillus, greater presence of other non-Lactobacillus genera, or the complement of bacteria consisting of urobiome community types remains to be determined.

Impact of microbiota and host immunologic response on the efficacy of anticholinergic treatment for urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Studies within the past decade have suggested associations among composition of the urinary microbiota, local immune responses, and urinary incontinence symptoms. To investigate these relationships, we evaluated the structure of the urinary microbiome, local inflammatory markers, and patient responses prior to and at 6-weeks after treatment with anticholinergic medication for urgency urinary incontinence (UUI). METHODS: Using a prospective pilot study, we enrolled women who presented with UUI symptoms and were prescribed treatment with anticholinergics. Catheterized urine samples were collected from participants at their baseline and 6-week follow-up visits for microbiological (standard and 16S rRNA gene phylotyping analyses) and cytokine analysis along with the UDI-6 questionnaire and 2-day bladder diary. RESULTS: Patients were Caucasian, post- menopausal, with a median age of 64 and median BMI of 30.1 kg/m2. Among the patients, 75% had UUI symptoms for less than 2 years, but with a frequency of at least a few times a week or every day. Most women were prescribed 10 mg oxybutynin ER daily at enrollment. Patients had varied urinary microbiota by culture and 16S phylotyping, with species of Lactobacillus being the most common, in six samples, in addition to taxa associated with Enterococcus, Staphylococcus, and mixed flora. Cytokine levels showed no differences before and after treatment with anticholinergics, nor correlation with urinary bacteria or microbiome composition. CONCLUSIONS: Our pilot study suggests factors in addition to the urinary microbiome and local immune responses may be involved in patients' response to anticholinergics for UUI.

The Urobiomes of Adult Women With Various Lower Urinary Tract Symptoms Status Differ: A Re-Analysis.

The discovery of the urinary microbiome (urobiome) has created opportunities for urinary health researchers who study a wide variety of human health conditions. This manuscript describes an analysis of catheterized urine samples obtained from 1,004 urobiome study participants with the goal of identifying the most abundant and/or prevalent (common) taxa in five clinically relevant cohorts: unaffected adult women (n=346, 34.6%), urgency urinary incontinence (UUI) (n=255, 25.5%), stress urinary incontinence (SUI) (n=50, 5.0%), urinary tract infection (UTI) (n=304, 30.4%), and interstitial cystitis/painful bladder syndrome (IC/PBS) (n=49, 4.9%). Urine was collected via transurethral catheter and assessed for microbes with the Expanded Quantitative Urine Culture (EQUC) technique. For this combined analytic cohort, the mean age was 59 ± 16; most were Caucasian (n=704, 70.2%), Black (n=137, 13.7%), or Hispanic (n=130, 13.0%), and the mean BMI was 30.4 ± 7.7. Whereas many control or IC/PBS cohort members were EQUC-negative (42.4% and 39.8%, respectively), members of the other 3 cohorts were extremely likely to have detectable microbes. The detected urobiomes of the controls and IC/PBS did not differ by alpha diversity or genus level composition and differed by only a few species. The other 3 cohorts differed significantly from the controls. As expected, Escherichia was both prevalent and highly abundant in the UTI cohort, but other taxa also were prevalent at more moderate abundances, including members of the genera Lactobacillus, Streptococcus, Staphylococcus, Corynebacterium, Actinomyces, and Aerococcus. Members of these genera were also prevalent and highly abundant in members of the UUI cohort, especially Streptococcus anginosus. Intriguingly, these taxa were also detected in controls but at vastly lower levels of both prevalence and abundance, suggesting the possibility that UUI-associated symptoms could be the result of an overabundance of typical urobiome constituents. Finally, prevalence and abundance of microbes in the SUI cohort were intermediate to those of the UUI and control cohorts. These observations can inform the next decade of urobiome research, with the goal of clarifying the mechanisms of urobiome community composition and function. There is tremendous potential to improve diagnosis, evaluation and treatment for individuals affected with a wide variety of urinary tract disorders.

Network-Based Differences in the Vaginal and Bladder Microbial Communities Between Women With and Without Urgency Urinary Incontinence.

Background: Little is known about the relationship of proximal urogenital microbiomes in the bladder and the vagina and how this contributes to bladder health. In this study, we use a microbial ecology and network framework to understand the dynamics of interactions/co-occurrences of bacteria in the bladder and vagina in women with and without urgency urinary incontinence (UUI). Methods: We collected vaginal swabs and catheterized urine specimens from 20 women with UUI (cases) and 30 women without UUI (controls). We sequenced the V4 region of the bacterial 16S rRNA gene and evaluated using alpha and beta diversity metrics. We used microbial network analysis to detect interactions in the microbiome and the betweenness centrality measure to identify central bacteria in the microbial network. Bacteria exhibiting maximum betweenness centrality are considered central to the microbe-wide networks and likely maintain the overall microbial network structure. Results: There were no significant differences in the vaginal or bladder microbiomes between cases and controls using alpha and beta diversity. Silhouette metric analysis identified two distinct microbiome clusters in both the bladder and vagina. One cluster was dominated by Lactobacillus genus while the other was more diverse. Network-based analyses demonstrated that vaginal and bladder microbial networks were different between cases and controls. In the vagina, there were similar numbers of genera and subgroup clusters in each network for cases and controls. However, cases tend to have more unique bacterial co-occurrences. While Bacteroides and Lactobacillus were the central bacteria with the highest betweenness centrality in controls, Aerococcus had the highest centrality in cases and correlated with bacteria commonly associated with bacterial vaginosis. In the bladder, cases have less than half as many network clusters compared to controls. Lactobacillus was the central bacteria in both groups but associated with several known uropathogens in cases. The number of shared bacterial genera between the bladder and the vagina differed between cases and controls, with cases having larger overlap (43%) compared to controls (29%). Conclusion: Our study shows overlaps in microbial communities of bladder and vagina, with higher overlap in cases. We also identified differences in the bacteria that are central to the overall community structure.

The Urinary Tract Microbiome: The Answer to All Our Open Questions?

CONTEXT: The dogma of a sterile urinary tract persisted for over a century. With the advances in new high-throughput sequencing technologies and modified culture protocols for microbiome research, we have discovered a variable microbial spectrum in the urinary tract. Its relevance for health and disease is now under investigation. OBJECTIVE: To present the latest insights into the role of the urinary tract microbiome in functional disorders. EVIDENCE ACQUISITION: Medline, PubMed, the Cochrane database, and Embase were screened for randomised controlled trials, clinical trials, and reviews on the urinary tract microbiome. EVIDENCE SYNTHESIS: The urinary tract is not sterile. Every individual harbours a complex microbial network in the urinary tract that is exposed to internal and external factors. Any imbalance in this network is likely to contribute to the development of lower urinary tract symptoms. Functional disorders such as interstitial cystitis, urinary urge incontinence, and chronic prostatitis/chronic pelvic pain syndrome, none of which include a bacterial origin for diagnosis, show features of an altered microbiome with specific dominating urotypes in contrast to urine from asymptomatic healthy individuals. The growing insights into the impact of the urinary microbiome on these entities may help in gaining a deeper understanding of the condition and may provide guidance for optimised management. CONCLUSIONS: The urinary tract is not sterile. The discovery of the urinary microbiome suggests that any imbalance may have a relevant role in the development of symptoms in functional disorders. PATIENT SUMMARY: The urinary tract is naturally colonised with a specific microbial spectrum for which impairment may cause bothersome symptoms.

The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls.

INTRODUCTION & HYPOTHESIS: Previous studies have suggested that women with urinary incontinence have an altered urinary microbiome. We hypothesized that the microbiome in women with mixed urinary incontinence (MUI) differed from controls and tested this hypothesis using bacterial gene sequencing techniques. METHODS: This multicenter study compared the urinary microbiome in women with MUI and similarly aged controls. Catheterized urine samples were obtained; v4-6 regions of the 16S rRNA gene were sequenced to identify bacteria. Bacterial predominance (> 50% of an individual's genera) was compared between MUI and controls. Bacterial sequences were categorized into "community types" using Dirichlet multinomial mixture (DMM) methods. Generalized linear mixed models predicted MUI/control status based on clinical characteristics and community type. Post-hoc analyses were performed in women < 51 and ≥ 51 years. Sample size estimates required 200 samples to detect a 20% difference in Lactobacillus predominance with P < 0.05. RESULTS: Of 212 samples, 97.6% were analyzed (123 MUI/84 controls, mean age 53 ± 11 years). Overall Lactobacillus predominance did not differ between MUI and controls (45/123 = 36.6% vs. 36/84 = 42.9%, P = 0.36). DMM analyses revealed six community types; communities differed by age (P = 0.001). A High-Lactobacillus (89.2% Lactobacillus) community had a greater proportion of controls (19/84 = 22.6%, MUI 11/123 = 8.9%). Overall, bacterial community types did not differ in MUI and controls. However, post-hoc analysis of women < 51 years found that bacterial community types distinguished MUI from controls (P = 0.041); Moderate-Lactobacillus (aOR 7.78, CI 1.85-32.62) and Mixed (aOR 7.10, CI 1.32-38.10) community types were associated with MUI. Community types did not differentiate MUI and controls in women ≥ 51 years (P = 0.94). CONCLUSIONS: Women with MUI and controls did not differ in overall Lactobacillus predominance. In younger women, urinary bacterial community types differentiated MUI from controls.

[Emphysematous cystitis: Report of one case]. / La cystite emphysémateuse : à propos d'un cas.

INTRODUCTION: Emphysematous cystitis is a rare urinary tract infection characterized by gas in the bladder wall and lumen. CASE REPORT: We report a 92-year-old women admitted with confusion and abdominal pain without fever. Her past medical history included diabetes, urinary incontinence, high blood pressure and mild cognitive impairment. A computed tomography scan (CT scan) revealed emphysematous cystitis. The patient completely recovered within ten days. The main characteristics and the treatment of this uncommon disorder are presented. CONCLUSION: Clinicians should be aware of this diagnosis: early management is essential to reduce morbidity and mortality.

Changes in the Vaginal Microenvironment as Related to Frequency of Pessary Removal.

OBJECTIVE: The aim of the study was to describe the effect of frequency of pessary removal on the vaginal microenvironment. METHODS: We performed a secondary analysis of a multicenter randomized trial of hydroxyquinoline gel in women presenting for pessary fitting. Patients had vaginal secretions analyzed at baseline, 2 weeks, and 3 months. Patients were stratified by frequency of pessary removal at least once daily, at least once weekly, and less often than once weekly. These groups were compared for prevalence of Lactobacillus predominance (primary outcome), anaerobic predominance, Mobiluncus prominence, vaginal symptoms, and bacterial vaginosis by Nugent criteria, and correction for confounding variables was performed. RESULTS: One hundred thirty-seven women were included in this analysis: 34 (25%) removed the pessary daily, 54 (39%) at least weekly, and 49 (36%) less often than once weekly. Women who removed the pessary less often than weekly were older (P < 0.01), using more hormone therapy (P = 0.03), and more likely to have bacterial vaginosis at baseline (P < 0.01). At 2 weeks, the predominance of Lactobacillus in the group removing pessary daily was higher (41% daily vs 24% weekly vs 9% longer, P = 0.03) and this persisted after confounder correction (P < 0.01). Women who removed their pessary less than weekly were more likely to have anaerobic predominance at 3 months (P = 0.04). CONCLUSIONS: Women who remove their pessaries less often than once weekly have an increased prevalence of anaerobes at 3 months, but no difference in vaginal symptoms or pessary satisfaction.

The Urinary Tract Microbiome in Health and Disease.

CONTEXT: The urinary tract, previously considered a sterile body niche, has emerged as the host of an array of bacteria in healthy individuals, revolutionizing the urology research field. OBJECTIVE: To review the literature on microbiome implications in the urinary tract and the usefulness of probiotics/prebiotics and diet as treatment for urologic disorders. EVIDENCE ACQUISITION: A systematic review was conducted using PubMed and Medline from inception until July 2016. The initial search identified 1419 studies and 89 were included in this systematic review. EVIDENCE SYNTHESIS: Specific bacterial communities have been found in the healthy urinary tract. Changes in this microbiome have been observed in certain urologic disorders such as urinary incontinence, urologic cancers, interstitial cystitis, neurogenic bladder dysfunction, sexually transmitted infections, and chronic prostatitis/chronic pelvic pain syndrome. The role of probiotics, prebiotics, and diet as treatment or preventive agents for urologic disorders requires further investigation. CONCLUSIONS: There is a microbiome associated with the healthy urinary tract that can change in urologic disorders. This represents a propitious context to identify new diagnostic, prognostic, and predictive microbiome-based biomarkers that could be used in clinical urology practice. In addition, probiotics, prebiotics, and diet modifications appear to represent an opportunity to regulate the urinary microbiome. PATIENT SUMMARY: We review the urinary microbiome of healthy individuals and its changes in relation to urinary disorders. The question to resolve is how we can modulate the microbiome to improve urinary tract health.

Female urinary microbiota.

PURPOSE OF REVIEW: The newly discovered female urinary microbiota has the potential to deepen our understanding of urinary tract health and disease, including common lower urinary tract conditions such as urinary incontinence and urinary tract infection. The spectrum of painful bladder disorders and other less common conditions also may benefit from additional research that includes consideration of the resident bacterial community of the female bladder. The present review provides a clinical context for the rapidly emerging research regarding the female urinary microbiota and its relationships with urinary tract conditions of interest. RECENT FINDINGS: Studies using culture-independent techniques confirm prior reports of bacteria that reside in the female urinary bladder. These resident communities, the female urinary microbiota, possess characteristics that differ between women affected by urgency urinary incontinence and matched, unaffected controls. Enhanced urine culture techniques permit cultivation of organisms, including uropathogens, missed by standard urine culture, but detected by culture-independent sequencing techniques. SUMMARY: New technology is available. Clinical laboratories can modify traditional standard urine culture methods to enhance detection of uropathogens. However, given the existence of the female urinary microbiota, the simple presence of bacteria in the lower urinary tract should not be taken as evidence of infection.

Candida albicans colonisation, continence status and incontinence-associated dermatitis in the acute care setting: a pilot study.

Candida albicans is the most prevalent human fungal commensal organism and is reported to be the most frequent aetiological organism responsible for infection associated with incontinence-associated dermatitis. However, it remains unclear whether incontinence predisposes a patient to increased Candida colonisation or whether incontinence acts as a trigger for Candida infection in those already colonised. The purpose of this observational cross-sectional study was to estimate colonisation rates of C. albicans in continent, compared to incontinent patients, and patients with incontinence-associated dermatitis. Data were collected on 81 inpatients of a major Australian hospital and included a pelvic skin inspection and microbiological specimens to detect C. Albicans at hospital admission. The mean age of the sample was 76 years (SD = 12.22) with 53% being male. Incontinent participants (n = 53) had a non-significant trend towards greater Candida colonisation rates at the perianal site (43% versus 28%) χ2 (1, N = 81) = 4·453, p = ·638 and the inguinal site (24% versus 14%) χ2 (1, N = 81) = 6·868, p = ·258 compared to continent patients (n = 28). The incontinent subgroup with incontinence-associated dermatitis (n = 22) showed no difference in colonisation rates compared to those without incontinence-associated dermatitis. Understanding the epidemiology of colonisation may have implications for the prevention of Candida infection in these patients.

Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity?

OBJECTIVES: Traditionally, the urinary tract has been thought to be sterile in the absence of a clinically identifiable infection. However, recent evidence suggests that the urinary tract harbors a variety of bacterial species, known collectively as the urinary microbiome, even when clinical cultures are negative. Whether these bacteria promote urinary health or contribute to urinary tract disease remains unknown. Emerging evidence indicates that a shift in the urinary microbiome may play an important role in urgency urinary incontinence (UUI). The goal of this prospective pilot study was to determine how the urinary microbiome is different between women with and without UUI. We also sought to identify if characteristics of the urinary microbiome are associated with UUI severity. METHODS: We collected urine from clinically well-characterized women with UUI (n = 10) and normal bladder function (n = 10) using a transurethral catheter to avoid bacterial contamination from external tissue. To characterize the resident microbial community, we amplified the bacterial 16S rRNA gene by PCR and performed sequencing using Illumina MiSeq. Sequences were processed using the workflow package QIIME. We identified bacteria that had differential relative abundance between UUI and controls using DESeq2 to fit generalized linear models based on the negative binomial distribution. We also identified relationships between the diversity of the urinary microbiome and severity of UUI symptoms with Pearson's correlation coefficient. RESULTS: We successfully extracted and sequenced bacterial DNA from 95% of the urine samples and identified that there is a polymicrobial community in the female bladder in both healthy controls and women with UUI. We found the relative abundance of 14 bacteria significantly differed between control and UUI samples. Furthermore, we established that an increase in UUI symptom severity is associated with a decrease in microbial diversity in women with UUI. CONCLUSIONS: Our study provides further characterization of the urinary microbiome in both healthy controls and extensively phenotyped women with UUI. Our results also suggest that the urinary microbiome may play an important role in the pathophysiology of UUI and that the loss of microbial diversity may be associated with clinical severity.

Bacterial uropathogens and antibiotic susceptibility of positive urine cultures in women with pelvic organ prolapse and urinary incontinence.

AIMS: The aims of the study are to describe the speciation and resistance patterns of positive urinary cultures in women with pelvic floor disorders (PFDs) and those undergoing pelvic reconstructive surgery. METHODS: Urine cultures with a colony count of >10(5) CFU and <3 isolated uropathogens at a tertiary care Urogynecology practice over a 5-year period for patients with anterior wall dominant pelvic organ prolapse (POP) or urinary incontinence (UI) were identified. Speciation and culture sensitivity data were described for each group and compared to a control group who did not currently have a PFD and who had not undergone pelvic surgery within a year of their positive culture. Additionally, early post-operative UTIs (≤6 weeks) and late post-operative UTIs (>6 weeks but ≤1 year) were compared. RESULTS: 1,306 positive urine cultures over the 5-year period with 51 different species of uropathogens were identified. The percentage of Escherichia coli identified was not significantly different between groups: POP 57.1%, Stress UI 58.4%, Urge UI 54.3%, non-operative controls 54.3%. Cultures obtained from patients on prophylactic antibiotics were significantly less likely to have E. coli (adjusted OR 0.45, 95% CI 0.22, 0.89, P < 0.0216). Non-E. coli cultures were more common in the early post-operative period compared to the late post-operative cultures (69% vs. 41%, adjusted OR 0.33, 95% CI 0.22, 0.48, P < 0.0001). CONCLUSIONS: Patients with PFDs who develop UTIs have rates of non-E. coli over 40% of the time. Treatment based on culture and antibiotic sensitivity data should be considered.

"Sterile Urine" and the Presence of Bacteria.

Adult human urine is not sterile. The resident bacterial community may contribute to urinary health and disease in undiscovered ways. Bacterial genomic sequencing and expanded urine culture techniques are major complementary tools for scientific exploration in urologic research.

The female urinary microbiome: a comparison of women with and without urgency urinary incontinence.

Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus. Nine genera (Actinobaculum, Actinomyces, Aerococcus, Arthrobacter, Corynebacterium, Gardnerella, Oligella, Staphylococcus, and Streptococcus) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. Importance: New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by urgency, frequency, and urinary incontinence. Given the significant overlap of UUI symptoms with those of urinary tract infections, it is possible that UUI may have a microbial component. We compared the urinary microbiomes of women affected by UUI to those of a comparison group without UUI, using both high-throughput sequencing and extended culture techniques. We identified statistically significant differences in the frequency and abundance of bacteria present. These differences suggest a potential role for the urinary microbiome in female urinary health.

[Treatment of chronic cystitis in postmenopausal women].

A randomized double blind controlled trial of intravaginal cream ovestin (estriol) was conducted in 102 postmenopausal females with chronic cystitis. The patients were divided into two groups. Group 1 (n = 52) received standard therapy, group 2 (n = 50) received standard therapy plus ovestin (daily intravaginal administration for 2 weeks, then twice a week). Final results were evaluated 1 year after therapy. Before the treatment 94% patients had subnormal levels of blood estradiol. One year after the treatment positive results were achieved in 91.3% patients of group 2 and 65.8% of group 1 (p < 0.001). In group 2 patients ovestin significantly reduced pollakiuria, nocturia, episodes of urgent urinary incontinence, painful voiding. Percentage of patients with leukocyturia diminished from 100 to 8%, bacteriuria--from 74 to 4%, with vaginal lactobacilli increased from 0 to 56%, enterobacterial contamination of the vagina fell from 66 to 12%. Vaginal pH decreased from 6.0 to 3.6. Addition of ovestin to standard therapy reduced the number of cystitis recurrences 11-fold, days of antibacterial therapy--12.4-fold. Side effects of ovestin (vaginal pruritus) were seen in 4% patients.