FEMALE UROLOGY Risk Factors for Women to Have Urodynamic Stress Urinary Incontinence at A Turkish Tertiary Referral Center: A Multivariate Analysis Study Sinharib Citgez,1* Bulent Onal,1 Sarper Erdogan,2 Cetin Demirdag,1 Merve Korkmaz,3 Oktay Demirkesen,1 Zubeyr Talat,1 Ahmet Erozenci,1 Bulent Cetinel1 Purpose: To investigate the risk factors in women with urodynamic stress urinary incontinence (USTIC) at a Turkish tertiary referral center. Materials and Methods: The urodynamic records of 3038 consecutive women were analyzed between 1990 and 2011. The patients who had etiological factor of neurologic disease were excluded. There were 1187 women who had USTIC after urodynamic investigation and 274 women who had no incontinence symptoms were included in the study. Multivariate analyses were done using logistic regression test to determine the risk factors for USTIC. Results: The mean age was 50.1 years (range, 86-18). Increased age, vaginal delivery, cesarean section, anterior prolapse existence in physical examination, previous anti-incontinence surgery, and previous pelvic organ prolapse surgery was found to be significant risk factors for USTIC at multivariate analyses. Conclusion: There are risk factors for women to have USTIC. Increased age, having vaginal delivery, having cesarean section, anterior prolapse, previous anti-incontinence surgery and previous prolapse surgery were found to be risk factors for women to have USTIC at this study. Keywords: Turkey; epidemiology; health behavior; pelvic floor; physiopathology; prevalence; prospective studies; urinary ıncontinence; stress. INTRODUCTION Stress urinary incontinence (SUI) is urinary incon-tinence (UI) during exertion, straining, exercise, coughing or sneezing.(1) SUI is a non-life threatening condition, but can have negative impacts on social and psychological status. UI will occur without detrusor contraction, if there is an inability of urethral closure mechanism (sphincter in- sufficiency) when abdominal pressure increases due to exertion, straining, exercise, coughing or sneezing un- der urodynamic observation. This type of incontinence is defined as urodynamic stress urinary incontinence (USTIC) in terminology of International Continence Society (ICS).(2) USTIC is an objective and valuable data for physicians to start treating SUI in patients. Many epidemiological studies have investigated po- tential risk factors for UI.(3-6) Increased age, gyneco- logical surgery, menopausal status, multiparity and etc. have been proposed as risk factors. We aimed to select frequently seen variables. We investigated the age, diabetes mellitus and pelvic organ prolapse (POP) as non-modifiable variables; and vaginal de- livery, cesarean section, previous anti-incontinence or POP surgery, previous pelvic surgery and hyster- ectomy as modifiable variables to be a risk factor for USTIC in this study. We aimed to investigate the risk factors in women with USTIC and help the other phy- sicians use our findings at their daily examinations. MATERIALS AND METHODS Study Population A total of 3038 women who had urodynamic tests in our clinic between 1990 and 2011 were retrospectively reviewed. Our urodynamic unit is a specialized clinic at our department. The archives of the patients are col- lected by a specialized nurse at our urodynamic unit. The cases were selected depending on our present mul- tivariate analyses study. Women who had neurological diseases were excluded. There were 1187 women who were diagnosed as USTIC after urodynamic examina- tion, and 274 women without urinary incontinence com- plaint were included in the study out of 1461 women. Vaginal examination with cough stress test, measure- ment of urine volume, urinary flow study and measure- ment of post voiding residual urine (PVR) were per- formed prior to multi-channel urodynamic study in our urodynamic unit. A multichannel urodynamic study, including the pressure-flow study, was also performed, if it is required. All urodynamic studies were performed according to the guidelines of the ICS.(7) Three physi- cians (BC, OD, BO) who were experienced and well trained in urodynamic study, analyzed patient’ medical records including questionnaires and the urodynamic studies of the patients retrospectively. All terms and definitions are in accordance with the ICS terminology. (2) The term USTIC, which was used in this study, was defined by ICS as the involuntary leakage of the urine 1 Department of Urology, Cerrahpasa School of Medicine, University of Istanbul, Istanbul, Turkey. 2 Department of Public Health, Cerrahpasa School of Medicine, University of Istanbul, Istanbul, Turkey. 3 Cerrahpasa School of Medicine, University of Istanbul, Istanbul, Turkey. *Correspondence: Kocamustafapasa Cd. No:53 34098 Fatih, Istanbul, Turkey. Tel: + 90 212 571 3570 . E-mail: drsinharib@yahoo.com. Rceived October 2014 & Accepted March 2015 Vol 12 No 03 May-June 2015 2187 during increased abdominal pressure in the absence of a detrusor contraction.(2) Approval for this study was given by Ethical Committee of Cerrahpasa School of Medicine, Istanbul University (IRB number: 32821). Statistical Analysis The dependent variable of the study was having USTIC. The independent variables of this study were age, vag- inal delivery, cesarean section, diabetes mellitus, POP, previous anti-incontinence surgery, previous POP sur- gery, previous pelvic surgery (colorectal operations and other gynecological operations such as oophorectomy), and hysterectomy. Numerical variables were expressed with mean and standard deviation (SD), while cate- gorical variables were expressed with frequency and percentage (%) values in this study. All independent variables were included in the logistic regression test. Menopausal status which can be independent variable of the study, was not included in multivariate analysis because of its correlation with age. Risk analysis was done separately for vaginal delivery and cesarean sec- tion. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Risk factors for USTIC were examined by using backward logistic regression in multivariate analysis. The entry and removal threshold P values were .05 and .10 for this study. Statistical analyzes were per- formed using Statistical Package for the Social Science (SPSS Inc, Chicago, Illinois, USA) version 15.0. The P value < .05 was accepted as statistically significant. RESULTS The mean age was calculated as 50.1 years (range, 18-86). In multivariate analysis; age, vaginal delivery, cesarean section, anterior prolapse finding in physical examination, previous anti-incontinence surgery and previous POP surgery were the significant risk factors for USTIC (Table 1). Increasing age was associated with increased detection of USTIC (OR = 1.03, 95% CI: 1.02-1.04; P < .001). Vaginal delivery and cesarean section were found to be independent risk factors for USTIC (OR = 2.81, 95% CI: 2.08-3.78; P < .001 and OR = 2.51, 95% CI: 1.47-4.30; P < .001, respectively). Anterior prolapse was found to be an independent risk factor for USTIC (OR = 2.56, 95% CI: 1.78- 3.76; P < .001), however posterior or apical prolapse were not. Previous anti-incontinence surgery and previous POP surgery were as independent risk fac- tors for USTIC (OR = 2.69, 95% CI: 1.18-6.15; P < .019 and OR = 2.30, 95% CI: 1.08-4.92, respective- ly), however hysterectomy or previous pelvic sur- gery were not. In addition, diabetes mellitus did not reach statistical significance as a risk factor for SUI. The risk analysis for vaginal delivery and cesarean sec- tion was assessed separately with univariate analysis. Calculated OR value was 3.66 (95% CI: 2.75-4.87) for having birth (Table 2). In addition, while OR for vaginal delivery was 3.09 (95% CI: 2.35-4.07), the value for ce- sarean delivery was not statistically significant (Table 3). DISCUSSION SUI is a common condition in women with a preva- lence of 35.5% in urology and obstetrics and gyne- cology outpatient clinics in our country.(8) It is similar in the other European countries with a prevalence of 35%.(9) The potential risk factors for SUI have been investigated in some epidemiological studies.(3-6) Age, diabetes mellitus, menopause, genetic factors, ischem- ic heart disease and lung disease have been considered as non-modifiable variables and pregnancy/childbirth, obesity/body mass index, hormone replacement thera- py, hysterectomy, smoking, diet and many other var- iables have been considered as modifiable variables risk factors for UI in existing literature,.(10-16) In this multivariate analysis study that we investigated the risk factors for USTIC in women, age was as a non-modi- fiable variable and vaginal delivery, cesarean section, Variables Number Adjusted Odds P Value Ratio (95% CI) Age 1461 1.03 (1.02-1.04) < .001 Vaginal delivery No 386 Reference < .001 Yes 1075 2.81 (2.08-3.78) Cesarean section No 1328 Reference < .001 Yes 133 2.51 (1.47-4.30) Anterior prolapse No 446 Reference < .001 Yes 1015 2.56 (1.78-3.76) Previous anti-incontinence surgery No 1364 Reference .019 Yes 97 2.69 (1.18-6.15) Previous pelvic organ prolapse surgery No 1336 Reference .032 Yes 125 2.30 (1.08-4.92) Previous pelvic surgery No 1093 Reference .067 Yes 368 0.54 (0.28-1.05) Previous hysterectomy No 1280 Reference .064 Yes 181 1.94 (0.96-3.94) Table 1. The multivariate predictors of urodynamic stress urinary incontinence (USTIC). Abbreviation: CI, confidence interval. Variables USTIC Total No Yes Number To have a birth No 113 (37.2) 191 (62.8) 304 (100.0) Yes 161 (13.9) 996 (86.1) 1157 (100.0) Total 274 (18.8) 1187 (81.2) 1461 (100.0) Abbreviations: USTIC, urodynamic stress urinary incontinence; OR, odds ratio; CI, confidence interval. * Data are presented as no (%). OR was 3.66 (95% CI: 2.75-4.87) for having a history of birth.* Table 2. The risk analysis for birth and USTIC. Risk Factors For SUI in Turkish Women-Citgez at al. Female Urology 2188 anterior prolapse, previous anti-incontinence surgery and previous POP surgery were modifiable variables. Recent many studies have found increased preva- lence of UI with increasing age.(3-5) Notwithstanding, UI is not inevitable with increasing age. However the bladder and the pelvic structures change with age, and these changes contribute to UI.(10) While stress type UI is common in young and middle-aged wom- en, urge type and mixed type UI is common in mid- dle-aged and older age.(5) Increasing age was found as a significant risk factor for USTIC in women in our study (OR = 1.03, 95% CI: 1.02-1.04; P < .001). SUI can be seen throughout pregnancy, especially in third trimester and generally improves after delivery. However, they may occur after delivery again and con- tinue.(11,12) In addition, women who have SUI in preg- nancy have higher risk for SUI throughout life, even if they recover after delivery.(13) The reason for this is un- clear. Physiological changes during pregnancy may be the cause of SUI. The patients who have chance to get SUI, might result in having the SUI because of the phys- iological changes regardless the pregnancy, or pregnan- cy might trigger the existing problem. There are many studies about UI at delivery and after delivery in exist- ing literature.(14,15) OR was 2.81 (95% CI: 2.08-3.78; P < .001) for vaginal delivery in our study. Some studies emphasized that the increased risk of UI by one labor, has not more increased even if the number of parity in- crease.(15) However, some contrary studies have demon- strated the increased risk of UI with increasing parity.(17) It is difficult to differentiate the risk at pregnancy and vaginal delivery. The risk at vaginal delivery may be explained by the injury caused by stretching of pu- dendal and other nerves or tissue damage that support pelvic floor.(18) The women who had vaginal delivery are compared to those who have cesarean section by the authors to reveal the differentiation between the impact of vaginal delivery separately from the impact of pregnancy itself for the risk of UI. Vaginal delivery compared with cesarean section was found to be a risk factor for incontinence in postpartum period, later in life and particularly for SUI in most of these studies.(19) Rortveit and colleagues, in their comprehensive studies that involved more than 15,000 women, have demon- strated increased risk for SUI and mixed UI (OR = 1.5) in women who had only cesarean section compared with nulliparous.(19) Furthermore, they demonstrated that those women who had only vaginal delivery have higher risk for SUI than women who had only cesarean section (OR = 2.4). The effects of different types of de- livery on UI have been addressed in some studies. The women, with vaginal delivery have greater risk (1.7 to 2.8 folds) for developing SUI compared with the wom- en who had cesarean section.(5,19) In the present study OR for vaginal birth was 2.81 (95% CI: 2.08-3.78; P < .001) and OR for cesarean section was 2.51 (95% CI: 1.47-4.30; P < .001) which demonstrates statistically significant difference. In addition, we performed uni- variate analysis to assess the risk analysis separately for vaginal and cesarean birth. As a result, calculated OR value was 3.66 (95% CI: 2.75-4.87) for having birth (Table 2). The estimated relative risk for vaginal birth was 3.09 (95% CI: 2.35-4.07), while the risk for cesar- ean section was not statistically significant (Table 3). POP and UI are common conditions in women and mostly seen together. Pelvic floor with fascia and mus- cles is important in maintaining continence and pelvic support. Due to factors such as changing of pelvic floor muscles and collagen structure, deterioration of conti- nence and pelvic support may be possible with aging and delivery. Support for the bladder neck is important, especially for SUI. The signs of pelvic denervation have been shown with increasing age and after birth,(20,21) and these changes are more common in women with POP or SUI.(22) In addition, authors against denervation hypoth- esis couldn’t find signs of denervation in pelvic floor at biopsies of women with POP and UI.(23) In Samu- elsson and colleagues’ studies that involves 641 young and middle-age women, demonstrated that women with anterior prolapse had higher risk for SUI and estimated relative risk was 2.5-fold (95% CI: 1.5-4.2).(17) Anterior prolapse was as a significant risk factor with an OR of 2.56 (95% CI: 1.78-3.76; P < .001) at our present study. Prior incontinence surgery was also found as a risk factor in the present study (OR = 2.69, 95% CI: 1.18- 6.15; P < .019). In fact, treatment failure and relapses are not unexpected situations. In these patients, the rea- sons for incontinence are still discussed that if it’s due to treatment failure, relapse or damage in pelvic nerves and pelvic support due to operation. Since we think that all of these factors may play a role, previous in- continence surgery was added to the statistical analysis and found to be an independent risk factor for USTIC. Effects of pelvic surgery and especially hysterectomy on UI in women are situations that were investigated and are still being researched.(24,25) As an example, the effect of POP surgery in SUI is complex. Sometimes after POP surgery, USTIC will improve and sometimes due to POP, SUI that was hidden will occur.(26) The POP surgery’s approach, injury to pelvic nerves and supporting structures may affect this result. As a result, POP surgery may be a risk factor for SUI. Previous POP surgery was found to be a risk factor for USTIC in the present study, (OR = 2.30, 95% CI: 1.08-4.92; P < .032). However in multivariate analysis, previous other pelvic surgeries (e.g., other gynecological oper- ations) were not found to be a risk factor (P = .067). Hysterectomy is thought that may cause to UI because of the damage to pelvic nerves and pelvic support struc- Table 3. The correlation between type of delivery and USTIC. Variables USTIC* Total No Yes Number Cesarean section No 255 (19.2) 1073 (80.8) 1328 (100.0) Yes 19 (14.3) 114 (85.7) 133 (100.0) Total 274 (18.8) 1187 (81.2) 1461 (100.0) Vaginal delivery USTIC* Total No Yes Number No 127 (32.9) 259 (76.1) 386 (100.0) Yes 147 (13.7) 928 (86.3) 1075 (100.0) Total 274 (18.8) 1187 (81.2) 1461 (100.0) Abbreviations: USTIC, urodynamic stress urinary incontinence; OR, odds ratio; CI, confidence interval. * Data are presented as no (%). OR was 3.09 (95% CI: 2.35-4.07) for vaginal delivery. Risk Factors For SUI in Turkish Women-Citgez at al. Vol 12 No 03 May-June 2015 2189 tures.(24,25) However, in a large proportion of the stud- ies, significant increase in UI after hysterectomy has not demonstrated.(27) In addition, some studies have shown statistically significant decrease of UI after hys- terectomy.(28) Although content of these studies is not high quality; the more comprehensive and prospective studies also have not found any increase in rate of UI in follow-up of patients with a history of hysterecto- my.(29) While the relationship between hysterectomy and UI was not shown in these prospective studies, UI was related to women with previous hysterectomy and estimated relative risk was ranged from 1.2 to 2.1 in some studies.(30) In a prospective study, urge incon- tinence was found to be related with hysterectomy but not stress incontinence.(31) As a result, relation- ship between hysterectomy and UI is not clear. In our study the multivariate analysis showed that hysterec- tomy does not increase the risk of USTIC (P = .064). There are several limitations in our study. One weakness of our study is that our data were collected retrospec- tively. The data were verified retrospectively while they were collected longitudinally and that might cause error. Our center is one of the major hospitals in our region. A total of 1461 consecutive women were included in this study. However, the majority of our patients were re- ferred from other hospitals; this may create an extensive patient selection bias and may influence our results. Our results suggest that; age, vaginal delivery, cesarean sec- tion, anterior prolapse finding in physical examination, previous anti-incontinence surgery and previous POP surgery were statistically significant risk factor for US- TIC in women. However, future studies should be pro- spectively designed to overcome existing limitations. CONCLUSION In summary, there are risk factors for USTIC in wom- en. In this multivariate study, age, vaginal delivery, cesarean section, anterior prolapse finding in vaginal examination, previous anti-incontinence surgery and previous POP surgery have found to be statistically significant risk factors for USTIC. Physicians should remember these modifiable variables and share with patients who will have vaginal delivery, cesarean sec- tion or other surgeries, mentioned above. However, there is no consensus to prevent SUI or USTIC in this patient group. In addition, age is a non-modifiable var- iable risk factor for USTIC in women during their life. CONFLICT OF INTEREST None declared. REFERENCES 1. Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010;21:5-26. 2. Abrams P, Cardozo L, Fall M, et al. 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