ANALYSIS OF RISK FACTORS FOR RECURRENT URINARY TRACT INFECTION IN WOMEN OF REPRODUCTIVE AGE : A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS AND PRIMARY OBSERVATIONAL STUDIES

Abstract

Introduction: Recurrent urinary tract infection is among the most common reasons for an otherwise healthy woman to consult a physician, and it is a principal driver of outpatient antimicrobial consumption worldwide. More than half of all adult women experience at least one urinary tract infection during their lifetime and approximately one quarter go on to experience recurrence. Although frequently framed as a disorder of the postmenopausal years, contemporary cohorts demonstrate a bimodal incidence with a distinct peak in the reproductive-age decades. The determinants operating in this younger stratum are behavioural, sexual, microbiological, and constitutional. This review aimed to identify, appraise, and quantitatively pool the risk factors for recurrent urinary tract infection in women of reproductive age.

Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020. Eligible designs included randomised controlled trials, cohort studies, case-control studies, cross-sectional studies, and other analytical observational designs. The population was premenopausal women aged 15–49 years. The outcome was recurrent urinary tract infection (≥2 episodes within 6 months or ≥3 within 12 months). Two reviewers independently screened, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale, RoB 2, and AXIS. Effect estimates were pooled on the logarithmic scale using DerSimonian-Laird random-effects models. Heterogeneity was quantified with Q, τ², and I²; small-study effects were examined with funnel plots and Egger's test. Certainty of evidence was rated with GRADE.

Results: Of 4,247 records, 32 studies met the criteria, with 18 contributing to at least one of six pooled outcome domains. Recent or frequent sexual intercourse was associated with a pooled odds ratio of 6.78 (95% CI 1.80–25.49; P = 0.005; I² = 90.5%). Exposure to spermicide, diaphragm, or spermicide-coated condoms yielded a pooled odds ratio of 2.78 (95% CI 1.70–4.57; P < 0.001; I² = 67.0%), with a clear exposure-response gradient. A prior history of urinary tract infection or a first infection at or before the age of 15 years gave a pooled odds ratio of 3.36 (95% CI 2.16–5.22; P < 0.001) with no detectable heterogeneity. A history of infection in first-degree female relatives yielded a pooled odds ratio of 3.26 (95% CI 2.14–4.97; P < 0.001; I² = 62.9%). Randomised modification of candidate risk factors (increased water intake, intravaginal lactobacillus repletion, cranberry proanthocyanidins, and D-mannose) produced a pooled risk ratio of 0.61 (95% CI 0.43–0.87; P = 0.006). The association between diabetes mellitus and recurrence differed markedly by stratum: the adjusted risk ratio was 1.07 (95% CI 1.04–1.10) in a reproductive-age-inclusive cohort of 374,171 women but 2.04 (95% CI 1.59–2.62) in pooled postmenopausal data, a ratio of ratios of 1.91 (95% CI 1.49–2.45; P = 4.2 × 10⁻⁷). Vaginal colonisation with Escherichia coli was present in 35% of cases versus 11% of controls.

Conclusion: In women of reproductive age, recurrent urinary tract infection is driven by a small number of strong, consistently replicated determinants. Spermicide-containing contraception, coital frequency, a personal or familial history of infection, vaginal lactobacillus depletion, low fluid intake, and recent antimicrobial exposure together account for most of the identifiable risk, and several of these are directly modifiable. Diabetes mellitus and other factors that dominate guidance written for older women should not be allowed to displace these determinants in the consultation with a younger woman. Clinicians should routinely elicit a contraceptive and sexual history and a structured family history, should advise an additional 1.5 litres of water daily where baseline intake is low, should consider intravaginal lactobacillus or cranberry preparations as antibiotic-sparing options, and should apply rigorous antimicrobial stewardship.