Predictors of Urinary Tract Infection after Menopause: A Prospective Study Sara L. Jackson, MD, MPH, Edward J. Boyko, MD, MPH, Delia Scholes, PhD, Linn Abraham, MS, Kalpana Gupta, MD, MPH, Stephan D. Fihn, MD, MPH PURPOSE: To describe the incidence of and risk factors for acute cystitis among nondiabetic and diabetic postmenopausal women. METHODS: We conducted a population-based, prospective co- hort study of 1017 postmenopausal women, aged 55 to 75 years, who were enrolled in a health maintenance organization and fol- lowed for 2 years. A wide range of behavioral and physiologic ex- posures were assessed at baseline interview and follow-up clinic visits; the main outcome measure was microbiologically confirmed acute symptomatic cystitis. Follow-up was 87% at 12 months and 81% at 24 months. RESULTS: During 1773 person-years of follow-up, 138 symp- tomatic urinary tract infections occurred (incidence, 0.07 per per- son-year). Independent predictors of infection included insulin- treated diabetes (hazard ratio [HR] = 3.4; 95% confidence interval [CI]: 1.7 to 7.0) and a lifetime history of urinary tract infection (HR for six or more infections = 6.9; 95% CI: 3.5 to 13.6). Borderline associations included a history of vaginal estrogen cream use in the last month (HR = 1.8; 95% CI: 1.0 to 3.4), a history of kidney stones (HR = 1.9; 95% CI: 1.0 to 3.7), and asymptomatic bacteri- uria at baseline (HR = 1.8; 95% CI: 0.9 to 3.5). Sexual activity, urinary incontinence, parity, postcoital urination, vaginal dryness, use of cranberry juice, vaginal bacterial flora, and postvoid residual bladder volume were not associated with incident acute cystitis after multivariable adjustment. CONCLUSION: Insulin-treated diabetes is a potentially mod- ifiable risk factor for incident acute cystitis among postmeno- pausal women, whereas a lifetime history of urinary tract infec- tion was the strongest predictor. Use of oral or vaginal estrogen was not protective, and a wide range of behavioral and physio- logic factors was not associated with acute cystitis episodes in this generally healthy sample. Am J Med. 2004;117:903–911. ©2004 by Elsevier Inc. U rinary tract infection is one of the most common community-acquired infections among women of all ages, affecting an estimated 11.3 million women in the United States annually, at a cost of $1.6 billion (1). As the numbers of postmenopausal women is projected to in- crease sharply in the coming decades (2), greater under- standing of the frequency of and risk factors for common infection, such as acute cystitis, is important. Among young, sexually active women, the major factors predisposing to urinary tract infection are frequency of sex- ual intercourse, type of contraceptive used, and prior symp- tomatic cystitis (3). The risk profile for postmenopausal women, however, is different. In case-control studies, peri- and postmenopausal women with acute cystitis have been more likely than controls to report urinary incontinence, a history of urinary tract infection, treated diabetes, a recent history of antibiotic use, recent sexual activity, and cold tem- perature exposure (4–6). Case-control studies, however, are limited by potential recall bias and difficulty ascertaining the temporal sequence between the exposure and occur- rence of acute cystitis. A large prospective cohort study in- volving women with coronary heart disease found that par- ity, vaginal itching, dryness, urge incontinence, treated diabetes, and poor overall health were associated with self- reported symptomatic cystitis (7). We conducted a prospective evaluation of microbio- logically confirmed urinary tract infection among com- munity-dwelling postmenopausal women. This popula- tion-based cohort study of 1017 women sought to determine the incidence of, and to evaluate a wide variety of potential risk factors for, acute cystitis. METHODS Study Design This 2-year prospective study was conducted at Group Health Cooperative, a group model health maintenance organization with about 450,000 members. Women aged 55 to 75 years were eligible to participate if they had no natural menstrual cycle in the preceding 12 months (oral or vaginal estrogen users were not excluded); resided in the Pierce, King, or Snohomish counties of Washington state; and had been enrolled in the group for at least 1 year. From Northwest Health Services Research and Development Program (SLJ, SDF), Epidemiologic Research and Information Center (EJB), VA Puget Sound, Seattle, Washington; Departments of Medicine (SLJ, EJB, SDF) and Epidemiology (DS), University of Washington, Seattle; Cen- ter for Health Studies (DS, LA), Group Health Cooperative of Puget Sound, Seattle, Washington; and Department of Medicine/Infectious Diseases (KG), Yale University, West Haven, Connecticut. Funding was provided by National Institutes of Health grants DK43134 and DK02660 to Dr. Gupta. This material is also the result of work supported with resources from and the use of facilities at the VA Puget Sound, Seattle, Washington. Dr. Jackson is a VA Health Services Research and Development Fellow. Requests for reprints should be addressed to Sara L. Jackson, MD, MPH, HSR&D (152), VA Puget Sound Health Care System, 1825 North 52nd Street, Seattle, Washington 98103, or sljack@u.washington.edu. Manuscript submitted February 3, 2004, and accepted in revised form July 9, 2004. © 2004 by Elsevier Inc. 0002-9343/04/$–see front matter 903 All rights reserved. doi:10.1016/j.amjmed.2004.07.045