Accepted Manuscript

Title: Obesity and recurrent urinary tract infections in

premenopausal women: a retrospective study
Author: William Nseir Raymond Farah Mahmud Mahamid
Helal Sayid Ahmad Julnar Mograbi Mohamed Taha Suheil
Artul
PII:
DOI:
Reference:

S1201-9712(15)00248-9
http://dx.doi.org/doi:10.1016/j.ijid.2015.10.014
IJID 2459

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International Journal of Infectious Diseases

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Revised date:
Accepted date:

17-9-2015
21-10-2015
21-10-2015

Please cite this article as: Nseir W, Farah R, Mahamid M, Ahmad HS, Mograbi J,
Taha M, Artul S, Obesity and recurrent urinary tract infections in premenopausal
women: a retrospective study, International Journal of Infectious Diseases (2015),
http://dx.doi.org/10.1016/j.ijid.2015.10.014
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Obesity and recurrent urinary tract infections in premenopausal women: a retrospective
study

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Highlights

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* The overall prevalence of RUTI in premenopausal women was 23.4 %.

* About a half of premenopausal women with recurrent urinary tract infections were

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obese.

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* Multivariate regression analysis showed that obesity (odds ratio = 4.00; 95% CI:

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3.24.61; p=0.001) was associated with RUTIs in premenopausal women.

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Obesity and recurrent urinary tract infections in premenopausal women: a

retrospective study

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William Nseir a, b, Raymond Farah b, c, Mahmud Mahamid b, d, Helal Sayid Ahmad a,

Julnar Mograbi a, Mohamed Tahaa, Suheil Artul a, b

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Division of Internal Medicine, EMMS, The Nazareth Hospital, Nazareth, Israel

Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel

Internal Medicine Department B, Ziv, Safed, Israel

Internal Medicine Department, Holy Family Hospital, Nazareth, Israel

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Dr. William Nseir

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Correspondence to

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Internal Medicine Department

EMMS, The Nazareth Hospital

Nazareth, P.O.B. 11, 16100, Israel

Tel: +972-4-602-8851, Fax: +972-74-755-9051
w.nseir@yahoo.com

Keywords: Obesity; Premenopausal women; Recurrent UTIs

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Obesity and recurrent urinary tract infections in premenopausal women: a

retrospective study

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Abstract

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Objectives: Data regarding the association between obesity and the risk of urinary
tract infections (UTIs), showing inconsistent results. This study aims to examine

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whether there is any association between obesity and recurrent UTIs (RUTIs) among

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premenopausal women.

Methods: A retrospective, case-control study which was conducted at outpatient

clinics of Internal Medicine of three hospitals. All consecutive premenopausal

women, nonpregnant aged 2055 years with RUTIs during two years were included

and compared with randomly selected women from outpatient clinics of internal

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medicine with no history of RUTI, age-matched 5 years. RUTI was defined as

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symptomatic UTI that follows the resolution of a previous UTI or three or more
symptomatic episodes over a 12-month period.

Results: We evaluated 691 premenopausal women with UTI during the study period.

Finally, 122 of 162 subjects with RUTIs were included in our study and compared
with 122 control cases without a history of RUTIs. The overall prevalence of RUTIs
among the premenopausal women was 23.4% (162/691). About a half of those with
RUTIs were obese. The mean age of women with RUTIs was 43.8 9 vs. 40 10 years
among the controls (p = 0.839). The mean BMI among women with RUTIs was

significantly higher than that of controls (35 4 vs. 26 3; P < 0.001). Multivariate

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regression analysis showed that obesity (odds ratio = 4.00; 95% CI: 3.24.61;
p=0.001) was associated with RUTIs in premenopausal women.

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Conclusions: Obesity was associated with RUTIs in premenopausal women.

1. Introduction

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Obesity has become a serious and worldwide public health problem 1-3. Obesity is

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associated with increasing mortality and morbidity from a variety of diseases

including: hypertension, diabetes mellitus, dyslipidaemia, metabolic syndrome,

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cardiovascular disease, and stroke 4-6. Recently, several studies have shown that
obesity was associated with infections. A retrospective study showed that obesity is

an independent predictor of blood stream infection 7. Other previous studies have

shown a correlation between obesity and septic shock, ventilator-associated

pneumonia 8, catheter-associated sepsis 9, H1N1 influenza infections 10, and

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Clostridium difficile infection 11. Moreover, obesity may alter the course of infection

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and seems to contribute to the progression of some chronic viral infections such as
hepatitis C 12-14.

Urinary tract infection (UTI) is one of the most commonly acquired bacterial
infections in ambulatory and hospitalized populations. Approximately 11% of all
women aged 18 years in the United States have a UTI each year. The incidence of
UTI is highest among women aged 1824 years, approaching 1 of 5 infections per
year 15.Among healthy women aged 1839, the 6-month risk of recurrence following
a first UTI is 24% 16. Approximately 5% of women with an initial UTI have multiple
episodes within a year. A recent large cohort study indicated that obesity is a risk

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factor for UTI 17. As regards pyelonephritis, the obese were nearly five times more
likely to be diagnosed than were the nonobese, females were at particularly higher
risk. Recently, a retrospective study done in Israel (using a computerized database)

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showed that obesity is independently associated with UTI particularly in males18.

Against this background, we conducted a retrospective study in order to examine

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whether there is any association between obesity and RUTIs in premenopausal

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women.

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2. Materials and methods

2.1. Subjects

We included consecutive premenopausal women with RUTIs who were presented

between June 2012 and May 2014 at outpatient clinics of Internal Medicine

Department of three hospitals (EMMS, The Nazareth Hospital, Nazareth; The Holy

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Family Hospital, Nazareth; Ziv Medical Centre, Safed) in Israel, with follow- up of at

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least one year for each case, aged 2055 years, and who did not receive antibiotic
prophylaxis for RUTIs. The exclusion criteria are: (1) pregnancy; (2) postmenopausal
women (3) women with malignancy with life expectancy less than one year, a human
immunodeficiency virus infection, using cranberry juice, permanent urinary catheter,
urinary tract stent, nephrostomy tube, urinary incontinence, neurogenic bladder,
asymptomatic bacteriuria, sexual transmitted diseases, connective tissue diseases,
kidney malformations, kidney stones, organ transplant, chronic use of corticosteroid
therapy, and substance abusers. Control cases (premenopausal women) randomly
selected from the same outpatient clinics of Internal Medicine Department, agematched 5 years without medical history of RUTI using the same exclusion criteria.

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The study was approved by each Hospital review board. The data were coded to
keep anonymity of the patients; informed consent was waived because of the noninterventional study design.
Study design

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2.2.

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This was a retrospective study, conducted in outpatient clinics of Internal Medicine

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Departments of three hospitals which aimed to examine the association between

obesity and RUTIs in premenopausal women. We compared between

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premenopausal women with and without RUTIs in term of maternal history of RUTIs,
use of contraceptive, use of probiotics, sexual intercourse, diabetes mellitus,

3.2. Clinical and laboratory data

metabolic syndrome and obesity.

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Data were obtained from the charts of all enrolled patients. The following
information was extracted: demographic, anthropometric measures, underlying

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diseases such as: diabetes mellitus, hypertension, hyperlipidaemia, and maternal

history of RUTIs. In addition we collected information about the drug therapy, use of
contraceptive, sexual intercourse, use of probiotics, results of laboratory analysis
including urinalyses and urine cultures were collected from medical charts. Any
covariate in the medical information or laboratory analysis that was not noted as
present was considered to be absent.
2.3.

Definitions

UTI was defined by clinical signs of dysuria and the urgency, frequency of urination
and the presence of fever, chills, and /or loin pain (pyelonephritis). The bacterial UTI

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included cystitis, urethritis, and acute pyelonephritis19. RUTI was defined as

symptomatic UTI that follows the resolution of a previous UTI or of three or more
symptomatic episodes over a 12-month period 20. All case patients had to have at

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least one culture-confirmed UTI. Obesity was defined as BMI 30 kg/m2. Diagnosis
of metabolic syndrome was based on the presence of at least three of the following

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indices: BMI 30 kg/m2, fasting blood glucose level > 100 mg/dL, serum triglyceride

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level >150 mg/dL, blood pressure >135/85 mmHg and serum high-density

lipoprotein cholesterol level < 50 mg/dL. These cut-off values for serum HDL

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cholesterol levels were based on those recommended by the National Cholesterol

Education Program Adult Treatment Panel III 21.

Statistical analysis

WinSTAT (Kalamia, Cambridge, MA, USA) was utilized for data handling and analysis.

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Mean values, standard deviations (SDs), and p values were calculated. We compared

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the two groups of premenopausal women with and without RUTIs in term of:
maternal history of RUTIs, use of contraceptive, use of probiotics, sexual intercourse,
diabetes mellitus, metabolic syndrome and BMI. For categorical variables the 2 test

was performed and for continuous variables Students t- test was used. Spearman
rank correlation and univariate regression analysis were used to determine the
strength of the relationship between the different risk factors including BMI and
RUTIs. A risk factor associated with a p value < 0.05 in univariate analysis was used
for feature analysis. Multivariate regression analysis was performed to determine
the association between the risk factors and RUTIs. Statistical significance was set at
5%.

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3. Results
We evaluated 691 premenopausal women with UTI during the study period. 162
subjects with RUTI were studied. Of them 40 cases were excluded (9 subjects with

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kidney stones; 8 with sexually transmitted diseases; 7 pregnant women; 6 on

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cranberry juice; 5 on antibiotic prophylaxis; 3 with neurogenic bladder; 2 with

malignancy). Finally, 122 premenopausal women with RUTIs met the inclusion and

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exclusion criteria of the study. The overall prevalence of RUTI among premenopausal
women was 23.4% (162/691). About a half of those with RUTI (49.5%) were obese,

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and the mean number of diagnosed episodes of UTIs was 3.90.4 per year. Table 1

shows the clinical and laboratory parameters of the cases with and without RUTIs.
No significant difference between the cases and controls in terms of age, use of

contraceptive, sexual intercourse, diabetes mellitus, and metabolic syndrome.

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However, maternal history of RUTIs, use of probiotics, and obesity were more

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significant in the cases of RUTIs than the controls.

Table 2 shows the results of multivariate regression analysis: maternal history of
RUTIs (odds ratio (OR) 1.6, 95% CI: 1.22.0, p = 0.05), no use of probiotics (OR = 1.90;
95% CI: 1.212.4, p = 0.05), and BMI > 30 kg/ m2 (OR = 4.0; 95% CI: 3.24.61, p =

0.001) were associated with RUTIs in premenopausal women.

Discussion

In this retrospective, case-control study we found that obesity was associated with
RUTIs in premenopausal women. According to our knowledge, this is the first study
evaluating the association between obesity and RUTIs in premenopausal women.

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The mechanisms underlying the association between obesity and infections are
under ongoing researches. Obesity is associated with a variety of diseases including
metabolic syndrome, and non-alcoholic fatty liver disease 4, 6, 22, 23. Obesity-related

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system dysregulation, decreased cell-mediated immune responses, and respiratory

dysfunction have been proposed as possible mechanisms 24- 26. The most important

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immunomodulatory adipokines in obesity are leptin, adiponectin, and the pro-

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inflammatory cytokines: TNF-, IL-6, and IL-1 27. Low levels of adiponectin in obesity
have been shown to alter the immune response, especially killer cell cytotoxicity and

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cytokine production by human myeloid cells 28.

Lactobacilli are the dominant bacteria of the vaginal flora and possess antimicrobial
properties that regulate the urogenital microbiota. Inadequate cure and recurrence

of genitourinary infections lead to a shift in the urogenital flora from a

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predominance of lactobacilli to coliform uropathogens. Therefore, the use of

lactobacillus-containing probiotics to restore the commensal urogenital flora has

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been proposed for the treatment and prophylaxis of RUTIs 29, 30. Recently, a meta-

analysis was done regarding Lactobacillus in the prevention of RUTIs in women 31.

Results showed that probiotics are safe and effective in preventing RUTIs. In our
study, the use of probiotics in the prevention of RUTIs was effective as we showed in
previous study32. However, there is a need for more RCTs in order to assess the use
of probiotics in UTIs.
Another finding of our study is the association between maternal history of UTI and
RUTIs. Several previous studies showed that a history of UTI in the mother is
associated with 23 fold increase in risk of UTI in her daughters 33, 34. This risk factor

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could reflect other shared environmental factors, or behaviours present in both

mothers and daughters. Genetic contribution in UTI has been studied in several
studies 35, 36. We believe that more genetic studies are needed in order to definitely

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evaluate this association.

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Our study has several limitations being a retrospective study with a relative small

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number of cases.

In conclusion, this study provides evidence that obesity could be associated with

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RUTIs in premenopausal women. However, more prospective studies are required to

assess this association and whether weight reduction will prevent the occurrences of

UTIs / RUTIs.

Competing interests

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The authors declare that have no competing interests.

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Table 1
Clinical and biochemical characteristics of study subjects

p-value

40 10
4 (3.2)
12 (9.8)
19 (15.7)
70 (57.4)
9 (7.3)
10 (8)
26 3

0.839
< 0.05
0.322
< 0.05
0.522
0.632
0.784
< 0.001

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43 9
21 (17.2)
15 (12.3)
5 (4.1)
65 (53.2)
8 (6.5)
13 (10.6)
35 4

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Age, years, mean SD

Maternal history of RUTIs, n (%)
Use of contraceptive, n (%)
Use of probiotics, n (%)
Sexual intercourse, n (%)
Diabetes Mellitus, n (%)
Metabolic syndrome, n (%)
Body mass index, (Kg/m2), mean SD

Controls
(n=122)

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Cases with RUTIs

(n =122)

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SD, standard deviation; RUTIs, recurrent urinary tract infections.

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TABLE 2

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Multivariate regression analysis showing the independent associations of BMI and RUTIs in
premenopausal women

1.60 (1.2-2.0)
1.90 (1.21-2.4)
4.00 (3.2-4.61)

0.05
0.05
0.001

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Maternal history of RUTIs

No use of probiotics
Body mass index > 30 kg/m2(obesity)

p-Value

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OR (95% CI)

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RUTIs, recurrent urinary tract infections; OR, odds ratio; CI, confidence interval.

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