Article Type: Clinical Article

CLINICAL ARTICLE
Accepted Article
Association of uterine leiomyoma and overactive bladder syndrome 

Marianne Koch 1,2,Tina Rauchenwald 1, Danijel Kivaranovic 3, Stephanie Schwab 4,5,

Wolfgang Umek 1,2, Heinz Koelbl 1, Michael Rauchenwald 6, Samir Helmy 1,5,*

1
Department of Obstetrics and Gynecology, Clinical Division of General Gynecology

and Gynecologic Oncology, Medical University of Vienna, Vienna, Austria

2
Karl Landsteiner Institut fuer Spezielle Gynaekologie und Geburtshilfe, Vienna,

Austria
3
Center for Medical Statistics, Informatics and Intelligent Systems, Medical

University of Vienna, Vienna, Austria

4
Department of Obstetrics and Gynecology, St. Josef Spital, Vienna, Austria
5
Karl Landsteiner Institut fuer Diagnostik und Therapie in der Frauenheilkunde,

Vienna, Austria
6
Department of Urology and Andrology, Sozialmedizinisches Zentrum Ost-

Donauspital, Vienna, Austria

* Corresponding author: Samir Helmy

Department of Obstetrics and Gynecology, Medical University of Vienna, Spitalgasse

23, 1090 Vienna, Austria

E-mail: samir.helmy@meduniwien.ac.at
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lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/ijgo.12545
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 Keywords: Benign pelvic tumor; Fibroid; Incontinence; Lower urinary tract
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symptoms; Overactive bladder syndrome; Transvaginal ultrasonography; Uterine

leiomyoma

Synopsis: The presence of anterior and/or fundal leiomyoma was found to be

significantly associated with overactive bladder syndrome.

 These data were presented as a poster at the Annual Meeting of the International

Urogynecology Association; June 9–13, 2015; Nice, France (2015-A-509-IUGA), and

at the Annual Meeting of the Austrian Society for Urogynecology and Reconstructive

Pelvic Floor Surgery; September 23–24, 2016; Baden, Austria.

Abstract

Objective: To assess associations between anterior and/or fundal uterine

leiomyoma and overactive bladder syndrome.

Methods: The present cohort study recruited women diagnosed with fundal/anterior

uterine leiomyoma by standardized transvaginal ultrasonography at the Medical

University of Vienna, Austria, between January 1, 2010, and December 31, 2013, in

addition to an age-matched control group of women without uterine leiomyoma. The

International Consultation on Incontinence Questionnaire Overactive Bladder Module

(ICIQ-OAB) was mailed to all eligible participants. The main outcome was the ICIQ-

OAB sum score.

Results: Among 304 questionnaires sent out, 129 were returned. After the exclusion

of incomplete datasets, 80 women were included in the analysis (uterine leiomyoma

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 group, 43; control group, 37). The mean±SD ICIQ-OAB sum score was 9.7±10.2 for

women with uterine leiomyoma and 4.2±5.3 for women in the control group; thus, the
Accepted Article
ICIQ-OAB sum score was on average 5.5 points higher in the uterine leiomyoma

group (P=0.003). The Spearman correlation coefficient between the total volume of

leiomyoma per woman and the ICIQ-OAB sum score was 0.072 (P=0.645).

Conclusion: The study found a significant association between anterior and/or

fundal leiomyoma and overactive bladder syndrome. The presence of uterine

leiomyoma should be ruled out during the evaluation of overactive bladder.

1 INTRODUCTION

Uterine leiomyoma are benign tumors that form in smooth muscle tissue within the

uterine myometrium. They represent the most common pelvic tumor in women of

reproductive age with an estimated prevalence of 20% among women older than 30

years [1,2].

Overactive Bladder (OAB) is defined by the International Continence Society as

symptoms of “urgency, with or without urge incontinence, usually with frequency and

nocturia.” Among women, OAB has an estimated prevalence of 13% (increasing to

20% for those older than 70 years) but can be as high as 48% if associated with

obesity [3,4]. The causes of non-neurogenic OAB are unknown, although neuronal,

myogenic, and inflammatory factors are likely to be involved in its development [5,6].

In addition, uterine leiomyoma may be associated with lower urinary tract symptoms

(LUTS) owing to the close anatomic relationship between, specifically, anterior

and/or fundal leiomyoma (hereafter anterior/fundal leiomyoma) and the urinary

bladder [7–9]. In a recent study of the prevalence of LUTS among women

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 undergoing surgery for uterine leiomyoma, the mean voiding subscale score was

higher for women with anterior fibroids than for women with fibroids in other locations
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[10].

Various other studies have reported postoperative changes in LUTS [11–13], and a

potential relationship between leiomyoma/large uterine volumes and increased LUTS

by using magnetic resonance imaging and ultrasonography [14, 15]. However, those

results were only secondary findings and were inconclusive on the type of LUTS.

To our knowledge, no study has prospectively investigated whether there is an

association between anterior/fundal uterine leiomyoma and overactive bladder

syndrome. The aim of the present study was therefore to investigate whether the

presence of anterior/fundal uterine leiomyoma is associated with this disorder.

2 MATERIALS AND METHODS

The present questionnaire-based cohort study recruited women who underwent

standardized transvaginal ultrasonography (TVUS) by a single expert sonographer

(SH) at the Department of Obstetrics and Gynecology at the Medical University of

Vienna, Vienna, Austria, between January 1, 2010, and December 31, 2013.

Institutional review board approval was obtained from the ethics committee of the

Medical University of Vienna (1443/2014). All participants gave written informed

consent before participating.

The following inclusion criteria were applied: age, 18–65 years, previous

standardized TVUS by a single expert sonographer, and diagnosis of fundal/anterior

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 uterine leiomyoma by TVUS. The exclusion criteria were diagnosis of any leiomyoma

other than anterior/fundal, diagnosis of neurologic disease affecting the lower urinary
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tract, and malignant disease of the lower urinary tract.

In addition to the study cohort, an age-matched control group of women was

recruited. The control group was selected from the same database on the basis of

the following criteria: previous TVUS within the selected time frame for gynecologic

reasons without a diagnosis of anterior or fundal leiomyoma, TVUS performed by the

same expert sonographer, age-matching to women in the leiomyoma group (±1

year).

Patient data regarding TVUS were retrospectively retrieved from the software

program PIA version 5.6.5.319 (GE Healthcare, View Point, Vienna, Austria)

including number, location (fundal, anterior, posterior), type (subserous, intramural,

submucous) and the dimensions of the uterine leiomyoma (in mm). Further patient

data were retrieved from the in-house hospital information system (KIS, Vienna,

Austria), including date and type of previous gynecologic surgery.

Each participant was sent the following documents by postal mail: a cover letter, two

copies of informed consent (one for return, one to keep), a specific study

questionnaire for assessment of general patient history, the International

Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB)

[16,17], and a sufficiently franked envelope with the hospital address to return the

questionnaire.

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 Women diagnosed with fundal or anterior leiomyoma who had had a previously

documented in-house operation for removal of leiomyoma (including hysterectomy,

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myoma enucleation and embolization) were sent two copies of the ICIQ-OAB

questionnaire. One was marked as “before surgery” and one as “after surgery” in

order to detect a possible difference in ICIQ-OAB score after the removal of uterine

leiomyoma. If, in the return mail, participants reported previous surgical removal of

leiomyoma that had been undertaken in a different hospital, they were sent an

additional mail including two ICIQ-OAB questionnaires (“before surgery” and “after

surgery”) and instructions for filling these in. Participants received a follow-up

telephone call if an answer was not received within 4 weeks.

All analyses were performed using R version 3.0.2 (The R Foundation, Vienna,

Austria). The main outcome measure was the ICIQ-OAB sum score. ICIQ-OAB

scores were compared between women with diagnosed uterine leiomyoma and

control women by t test. Paired t test was used to assess changes in the ICIQ-OAB

sum score after surgical removal of uterine leiomyoma. The χ2 test was used to

compare categorical variables. Spearman rank correlation was used to assess an

association between the volume of the largest uterine leiomyoma and ICIQ-OAB

sum score. P<0.05 or less was considered statistically significant.

3 RESULTS

The database search identified 193 women with fundal/anterior leiomyoma

diagnosed by TVUS during the study period. Of these, 40 were excluded for non-

documented postal address (n=13), not meeting the inclusion criteria (n=26), and

death (n=1). Consequently, 153 women diagnosed with fundal/anterior leiomyoma

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 were included in the study; accordingly, 153 patients without any uterine leiomyoma

were contacted for recruitment to the control group. Two women with leiomyoma
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were subsequently excluded because their documented addresses were not in

Austria. Therefore, the final study eligible population consisted of 304 women (151 in

the leiomyoma group and 153 in the control group).

Among the 304 questionnaires that were mailed, 129 were returned to the study

center (68 in the leiomyoma group and 61 in the control group), a follow-up rate of

42%. Among the women with leiomyoma, 43 return mailings were complete

(correctly filled-in ICIQ-OAB questionnaire and general questionnaire, with signed

informed consent) and 25 were excluded (12 had missing data, one had an ongoing

pregnancy, seven did not give informed consent, and five letters were returned as

undeliverable). Of the 43 complete returns, 29 women had not undergone surgical

removal of leiomyoma, whereas 14 reported having had surgical removal of

leiomyoma (11 of intramural leiomyoma, one of submucous leiomyoma, and two of

subserous leiomyoma). Three of these women, including the patient with submucous

leiomyoma, reported a hysterectomy. Each of the 14 women with surgical removal of

leiomyoma completed two ICIQ-OAB questionnaires, corresponding to before

surgery and after surgery.

In the control group (61 patients), 37 return mails were complete, and 24 were

excluded (14 for missing data, one had an ongoing pregnancy, one did not provide

informed consent, seven were undeliverable, and one patient had died).

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 Overall, data from 80 women (43 in the leiomyoma, group, and 37 in the control

group) were included in the statistical analysis. There were no significant differences
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in demographic characteristics between the two groups of women (Table 1).

The mean ± SD ICIQ-OAB sum score among women with leiomyoma was 9.7 ±

10.2, whereas that among control women was 4.2 ± 5.3 (Figure 1). Thus, the ICIQ-

OAB sum score was on average 5.5 points higher in the uterine leiomyoma group

than in the control group (P=0.003).

The group of women with uterine leiomyoma was subdivided into those with and

those without surgical removal of uterine leiomyoma. The mean difference in ICIQ-

OAB sum score between those with leiomyoma prior to surgical removal (i.e.,

women who completed the ICIQ-OAB questionnaire for before surgery, n=14) and

those with leiomyoma but no surgical removal (n=29) was 3.3 (P=0.400).

The mean difference in ICIQ-OAB sum score differed significantly when compared

between the pre-surgical scores of women with leiomyoma who underwent surgical

removal and the control group (7.7; P=0.048), and when compared between women

with leiomyoma who did not undergo surgical removal and the control group (4.4;

P=0.020).

ICIQ-OAB sum scores were compared among the 14 women with uterine leiomyoma

who underwent surgical removal. The ICIQ-OAB score decreased by 4.4 points on

average following surgery; however, the difference was not statistically significant

(paired t test P=0.078) (Figure 2).

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 Whereas the mean number of uterine leiomyoma did not differ between patients who
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underwent surgical removal and those who did not (1.4±0.7 vs 1.6±0.9, respectively;

P=0.653), women who under surgical removal demonstrated a significantly higher

total volume of leiomyoma compared with women who did not undergo surgical

removal (161.8± 190.2 cm3 vs 17.1±33.2 cm3, respectively; P=0.014). There was no

correlation between the total volume of uterine leiomyoma and the ICIQ-OAB sum

score (r=0.07; P=0.645) (Figure 3).

4 DISCUSSION

The study found that women with anterior/fundal leiomyoma presented significantly

higher ICIQ-OAB sum scores compared with those without uterine leiomyoma

(P=0.003). The ICIQ-OAB sum score was, on average, 5.5 points higher for women

with uterine leiomyoma than for those without. Thus, the present findings suggest

that there is an association between the presence of anterior/uterine leiomyoma and

overactive bladder syndrome. The findings are most probably explained by the

anatomic proximity of the uterus to the urinary bladder such that the uterine

leiomyoma compress the urinary bladder wall and trigger symptoms of urinary

urgency and/or frequency [7–9].

It has been speculated that the volume of the uterus and/or total volume of

leiomyoma, as well as the location, has an impact on the development of LUTS [10].

The present study did not find a correlation between the volume of uterine

leiomyoma and the ICIQ-OAB sum score, although there was an association

between the presence of anterior/fundal leiomyoma and OAB. These findings

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 suggest that the total volume of leiomyoma might have less impact on the

development of OAB relative to their location. This is the first study, to our
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knowledge, to address this issue specifically rather than as a secondary outcome.

The study had some strengths. All ultrasonography measurements of uterine

leiomyoma were standardized and performed by one expert sonographer, and a

validated standardized questionnaire (ICIQ-OAB) was used to evaluate overactive

bladder syndrome among women with and without uterine leiomyoma. Demographic

characteristics (including age, body mass index, menopausal status, obstetric

history, and other diseases) were similar between women with uterine leiomyoma

and those without, indicating equal exposure to risk factors for uterine leiomyoma

and OAB (Table 1).

The study also had limitations. First, the follow-up rate of 42% was low.

Nevertheless, 80 patients were included in the final analysis, representing one of the

largest study populations on this topic. Second, participants were not interviewed

directly by a medical doctor but completed the forms independently; this could

introduce a bias. However, the ICIQ-OAB is a validated questionnaire designed for

independent use by patients [17]; further, participants who returned incomplete or

inadequately filled questionnaires were excluded.

Finally, for the 14 patients with uterine leiomyoma who had had previous surgery

including leiomyoma removal, the ICIQ-OAB marked as before surgery was used for

statistical analysis. This could introduce recall bias because the women might have

undergone surgery several years before the date of investigation. However, there

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 was no significant difference in the ICIQ-OAB symptom score between women with

previous removal (score before surgery) and those without previous removal
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(P=0.3999). In addition, the maximum interval between surgery for uterine

leiomyoma and date of investigation was 4 years, because only women from the

database who had undergone transvaginal ultrasonography after 2010 were

included.

Among the 14 women with previous removal of uterine leiomyoma, we observed that

the ICIQ-OAB sum score remained relatively unchanged before and after surgery for

women with previously low sum scores (indicating a good bladder function), whereas

an overall change of ICIQ-OAB sum score was observed in women with a high pre-

operative ICIQ-OAB sum score (indicating a poor bladder function). The ICIQ-OAB

sum score decreased by 4.4 points on average, however, the finding was not

significant. The lack of significance of these findings could be explained by the low

sample size. However, the data suggest, collectively, that women with OAB

symptoms could benefit from surgical removal of their fibroids.

In conclusion, a significant association between anterior/fundal leiomyoma and

overactive bladder syndrome was observed; however, there was no correlation

between the total volume of uterine leiomyoma and the ICIQ-OAB sum score. These

findings suggest that, as compared with location, the total volume of leiomyoma

could have less impact on the development of overactive bladder syndrome. Ruling

out the presence of anterior/fundal uterine leiomyoma during the evaluation of

overactive bladder in women is recommended because removal of leiomyoma could

lead to relief of symptoms and thus improvement in quality of life.

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 Author contributions
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MK and SH contributed to the conception and design of the study; the collection,

management, and analysis of data; and writing and revising the manuscript. TR

contributed to the conception and design of the study; the collection and

management of data; and revising the manuscript. DK contributed to the conception

and design of the study; the analysis of data; and revising the manuscript. SS and

WU contributed to the conception and design of the study; the collection of data; and

revising the manuscript. HK and MR contributed to the conception and design of the

study, and revising the manuscript.

Acknowledgements

Financial support for the conduction of this study was provided by the Department of

General Gynecology and Gynecologic Oncology, Medical University of Vienna,

Vienna, Austria.

Conflicts of interest

The authors have no conflict of interest.

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Figure 1 Boxplot of median ICIQ-OAB sum score for women with leiomyoma and

those without leiomyoma. The box indicates the upper and lower quartiles and

outliers are illustrated as dots. Abbreviation: ICIQ-OAB, International Consultation on

Incontinence Questionnaire Overactive Bladder Module.

Figure 2 Postoperative change in the ICIQ-OAB sum score among women with

leiomyoma (n=14). Abbreviation: ICIQ-OAB, International Consultation on

Incontinence Questionnaire Overactive Bladder Module.

Figure 3 Correlation between the total volume of uterine leiomyoma and ICIQ-OAB

sum score. Abbreviation: ICIQ-OAB, International Consultation on Incontinence

Questionnaire Overactive Bladder Module.

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 Table 1 Demographic characteristics of women with and without uterine leiomyoma a
Characteristic Leiomyoma (n=43) No leiomyoma (n=37) P value b
Age, y 48±8.0 45±8.1 0.138 c
BMI 23±3.3 23±3.4 0.556 c
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Parity 0.7±1.0 1.1±0.9 0.149 c
No. of prior cesarean 0.2±0.5 0.3±0.7 0.298c
deliveries
Menopause 0.344
Premenopausal 31 (72) 23 (62)
Postmenopausal 12 (28) 14 (38)
Current smoker 0.636
Yes 10 (23) 7 (19)
No 33 (77) 30 (81)
Medication 0.987
Yes 21 (49) 18 (49)
No 22 (51) 19 (51)
Neurologic disease 0.101
Yes 3 (7) 0
No 40 (93) 37 (100)
Diabetes
Yes 0 0
No 43 (100) 37 (100)
Previous urinary tract 0.151
infection d
Yes 7 (16) 11 (30)
No 36 (84) 26 (70)
Other diseases 0.162
Yes 2 (5) 5 (14)
No 41 (95) 32 (86)
Previous operations 0.076
Yes 37 (86) 36 (97)
No 6 (14) 1 (3)
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by the square of height
in meters).
a
Values are given as mean ± SD or number (percentage) unless stated otherwise.
b
Asymptotic (2-sided) χ2 test unless indicated otherwise.
c
t test of independent samples.
d
More than three urinary tract infections within the past year.

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