Int Urol Nephrol
DOI 10.1007/s11255-016-1248-5
UROLOGY - REVIEW
Urological complications of uterine leiomyoma: a review
of literature
Gautam Dagur1 · Yiji Suh1 · Kelly Warren1 · Navjot Singh1 · John Fitzgerald2 ·
Sardar A. Khan1,2,3 
Received: 13 January 2016 / Accepted: 13 February 2016
© Springer Science+Business Media Dordrecht 2016
Abstract  results in urological and sexual symptoms. Leiomyoma
Introduction  Uterine leiomyomas are common gyneco-
logic tumor in reproductive-aged women, by age 50, diag-
nosis shared by urologist, gynecologists and radiologists.
Objective  The goal of this article is to review the current
literature, study the impact of leiomyoma on female lower
urinary tract, examine the cause female sexual dysfunction
and provide a comprehensive review of current diagnostic,
imaging studies, and current treatment of leiomyoma.
Methods  Clinical leiomyoma studies published from
1956 through 2015 were identified using the PubMed
search engines and the key words leiomyoma, fibroid in
the current literature. Impact of leiomyoma on the lower
urinary tract including female sexual dysfunction was
reviewed with terms of “urinary retention”, “bladder”,
“urethra”, “dyspareunia”, “incontinence”, “incomplete
bladder emptying”, “female sexual dysfunction”, and
“lower urinary tract” to study the urological and sexual
effects of leiomyoma. Literature related to leiomyoma was
reviewed from 1965 to present.
Results  Women with uterine leiomyomata complained of
pelvic pain, menstrual irregularities, infertility, lower uri-
nary tract symptoms and sexual dysfunction.
Conclusion  Leiomyoma is a common tumor of the uterus
that often clinically impacts on the lower urinary tract and
* Sardar A. Khan
skysalik@gmail.com
1
Department of Physiology and Biophysics, SUNY at Stony
Brook, Stony Brook, NY 11794, USA
2
Department of Urology, SUNY at Stony Brook, Stony Brook,
NY 11794, USA
3
HSC Level 9 Room 040 SUNY at Stony Brook, Stony
Brook, NY 11794‑8093, USA
can compress and grow into and become adherent to the
bladder and surrounding pelvic organs or metastasize into
peritoneal organs. Leiomyoma can enlarge and compress
the urinary bladder, urethra, and lower end of the ureters.
Leiomyoma can cause embarrassing sexual dysfunction
in females. Current literature of non-surgical and surgical
therapy of leiomyoma is described.
Keywords  Uterine leiomyoma · Hydronephrosis · Acute
urinary retention · Hematuria · Hysterectomy · Lower
urinary tract symptoms
Abbreviations
ECM Extracellular matrix
Bcl-2 Beta cell lymphoma-2
GPER G-protein estrogen receptors
AUR Acute urinary retention
LUTS Lower urinary tract symptoms
BN Barrington’s nucleus
Introduction
Uterine leiomyomas are benign neoplasms of smooth mus-
cle that originate in the myometrium [1]. They are also
known as fibroids, referring to the amount of collagen
found within the masses. Incidence of leiomyomas can be
as high as 70–80 % in women by age of 50, with highest
rates among African-American women [2]. Leiomyomas
can become symptomatic, with greater incidence among
nulliparous women. Although specific causes of uterine lei-
omyomas are unknown, leiomyomas may be due to hormo-
nal and genetic factors [3, 4]. Our objective is to compile
recent literature to provide a comprehensive understanding
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 Int Urol Nephrol

of uterine leiomyoma as well as its urological manifesta- tamoxifen in cancer cell creation [13]. Although this study
tions and complications of the urinary tract. Clinical mani- conducted focused primarily on breast cancer progression,
festations of uterine leiomyoma on female urinary tract there may be a correlation with uterine leiomyomas as the
have not been addressed in major textbooks. GPER in cancerous fibroblasts can produce collagen that
eventually metastasizes to uterine walls. It is also interesting
to note that elevation of estrogen levels correlate not only to
Molecular and genetic aspects of uterine breast cancer but also to uterine leiomyomas [14]. Targeting
leiomyomas future research on GPER represents possible development
for future potential uterine leiomyoma therapy.
The specific etiology of leiomyomas is currently unknown,
but studies suggest that leiomyoma may arise by pheno-
typic mutation of a single myometrial smooth muscle cell, Anatomical classification of leiomyomas
which stimulates cell proliferation and results in production
of excess extracellular matrix (ECM). Leiomyomas create Leiomyomas are divided based on location and position in
a hyperestrogenic environment necessary for leiomyoma the uterus (Table 1).
growth and maintenance. Leiomyomas have high con-
centrations of estrogen and progesterone receptors which
assists in greater estradiol binding [5]. Increased estrogen Clinical examination
and progesterone production leads to leiomyoma growth;
therefore, it is not uncommon for women on oral contra- Symptoms
ceptive to see increased growth of leiomyomas [6, 7]. In the
past, progesterone influenced the production of leiomyoma Leiomyomas tend to be asymptomatic in most women but
with apoptosis and generation of extraneous cells. How- a third of women experience further growth and symptoms
ever, Bulun et al. [3] suggests progesterone may have a role (Table 2).
in the growth of leiomyomas. Highly expressed beta cell
lymphoma-2 (Bcl-2) is able to prevent apoptosis. This gene Physical examination
is prevalent during the secretion phase of the menstrual
cycle and less when progesterone is released. Increase in Physical examination may fail to detect small leiomyomas.
Bcl-2 protein may be the cause of increased cell growth by Palpation of leiomyoma is dependent on the anatomical
prevention of cell death [8].
Table 1  Anatomical classification of leiomyomas
ECM proliferation, in uterine leiomyomas, is upregu-
lated by the promoter protein TGFβ3 [9] which is known Extrapelvic leiomyoma Intrapelvic leiomyoma
to interact with dermatopontin and thrombospondin [10]. Round ligament myomata [15] Intramural myomata [16]
Integrin proteins play a critical role in the shape and growth Submucosal myomata [16]
of leiomyomas. The most critical integrin protein is integ-  Protruding myomata [17]
rin β1, which is upregulated in leiomyomas [11].
Subserosal myomata [18, 19]
Alterations in chromosomes have been linked to leio-
Pedunculated myomata
myoma growth. Chromosomes 6, 7, 12, and 14 are found to
 Subserosal [18]
correlate with rates of leiomyoma growth [12]. Mehine et al.
 Submucosal [17]
[4] suggest that there are four emerging molecular classifi-
Parasitic myomata [1, 20]
cations: high rates of MED12 gene mutations, deletions of
Interstitial myomata [21]
COL4A5-COL4A6 genes, increased HMGA2 expression,
Cervical myomata [22]
and FH inactivation. More studies are necessary to compre-
Broad ligament myomata [23]
hend the genetic pathogenesis of uterine leiomyoma.
Wu et al. state G-protein estrogen receptors (GPER)
play an important role in tamoxifen-related uterine pathol- Table 2  Common symptoms of uterine leiomyomas
ogy, causing thickening and bleeding of the endometrium. Symptoms
Tamoxifen is a selective estrogen receptor modulator that
 Menorrhagia [24]
functions as an agonist and antagonist depending on the
 Pelvic discomfort [25]
target tissue. In endometrium, tamoxifen works as an estro-
 Dysmenorrhea [26, 27]
gen receptor antagonist. Changing estrogen receptor-α and
 Infertility [28]
isoforms of the receptor along with G-protein-coupled
 Miscarriage [29, 30]
receptor 30 in endometrial cells has been proven to control

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Int Urol Nephrol
Table 3  Imaging modalities for uterine leiomyomas
Imaging modalities
Dynamic real time transvaginal ultrasound [31, 32]
 With empty bladder
 With bladder distension
Abdominal ultrasound [31]
Transrectal ultrasound [33]
 With bladder distension
 With empty bladder
Plain radiography [19]
Computerized tomography (CT) [34]
CT with 3-dimensional reconstruction
Magnetic resonance imaging (MRI) [34, 35]
Stand up MRI with valsalva
MRI with 3-dimensional reconstruction
MR angiogram [36]
Hysterosalpingography [19]
location of leiomyoma. Bimanual pelvic examination,
including rectal and pelvic examination, may reveal palpa-
ble leiomyoma with pelvic tenderness. Speculum examina-
tion and optional proctoscopy may complete the physical
diagnosis.
Imaging methods
Leiomyomas are often detected during a pelvic exam.
However, imaging studies are utilized to identify anatomi-
cal locations, size, and impact on urinary tract (Table 3).
Instrumental exam
Diagnosis for leiomyomas with instruments and video-
urodynamics helps identify their anatomical locations and
impact on bladder-urethra and upper urinary tract (Table 4).
Urological complications of leiomyomas
Pathogenesis of urological complications
Urological complications may develop depending on the
anatomical locations, size, growth, and the leiomyoma sar-
comatous changes. Growth of a leiomyoma in the broad
ligament can result in obstruction of the bladder outlet and
paravaginal obstruction, resulting in urinary retention [41].
Intrapelvic leiomyoma can protrude anteriorly and inferiorly
from the uterus and press onto the bladder. Leiomyomas
rely on angiogenesis to allow for growth [42]. Therefore,
Table 4  Instrumentation for diagnosis of uterine leiomyomas
Instruments for diagnosing
 Hysteroscopy [37]
 Speculum examination [38]
 Cystoscopy [39]
 Diagnostic laparoscopy [40]
 Video-urodynamics
angiogenesis occurs upon protruding onto the bladder, and
contraction of the bladder ruptures these vessels which may
result in hematuria. Parasitic leiomyoma dislodges from
their site of origin and can travel to a different region of the
body. Certain times, they can result in unilateral ureteral
obstruction [43]. Uterine leiomyoma, growing superiorly,
can protrude onto the ureter and result in obstruction. This
may cause urine backflow and hydronephrosis.
Urethral obstruction
Several case reports describe acute urinary retention (AUR)
in patients with leiomyoma [13, 44, 45]. Yazdany et al.
[46] states, AUR can be caused when uterine leiomyomas
cause a superior and anterior rotation of the cervix, which
ultimately causes urethral or bladder-neck compression.
During urination, the cervix rotates away from the urethra.
Proposed mechanism relating AUR secondary to uterine lei-
omyomas results from obstruction of proximal urethra and
bladder neck, associations with premenstrual pelvic conges-
tion, and neuropathy of the pudendal or sacral nerves [13].
Angle variations of the bladder neck and urethral mobility
demonstrate the physical differences between continent and
incontinent women. Straining while in the supine position
does not cause obstruction in the urethral range of motion as
the average rotational angle of the bladder neck ranges from
21° to 44°, with an average of 32°. The bladder neck angle,
the angle of the urethrovesical junction located behind the
pubic symphysis, ranges at a normal level between 83° and
107° with an average of 95°. In contrast, continent pregnant
females have different ranges of −8° to 56° with an aver-
age of 19° for the urethral mobility, and a range of 38°–80°
with an average of 65° for the resting bladder neck angle.
The range of urethral mobility is more limited in incontinent
patients, while bladder neck angle is greater in range [47,
48]. If untreated, AUR can result in permanent damage to the
detrusor muscle, resulting in bladder trabeculation, bladder
diverticula, and vesicoureteral reflux [49].
Ureteral obstruction/hydronephrosis
Patients with uterine leiomyoma can develop obstruc-
tive uropathy, either unilateral or bilateral secondary
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 Int Urol Nephrol

ureteral obstruction causing hydronephrosis. Mirsadraee

et al. discuss 10 patients suffering from hydronephrosis.
Patient complaints include menorrhagia, dysmenorrhea,
pain, and mild renal impairment. In all cases, large leio-
myomas compressed the ureter at the pelvic brim. Uter-
ine artery embolization resolved the hydronephrosis and
relieved ureteral obstruction, relieving symptoms as well
[50].
Lai et al. [51] suggest that hypertension, resulting from
obstruction of the kidneys, leads to decreased glomerular
filtration rate by increased pressure in the Bowman’s cap-
sule. More studies are necessary to determine the relation-
ship between hypertension and hydronephrosis. Prolonged
uterine prolapse, due to uterine leiomyoma, can result in
hydronephrosis [52].

Lower urinary tract symptoms (LUTS)

Stewart et al. present a case in which a woman experiences

heavy menstrual bleeding, nocturia, and urinary frequency.
Diagnostic study indicated uterine leiomyoma could poten-
tially have caused these symptoms [53]. Parker-Autry et al.
conducted a survey where patients with uterine leiomyoma
experience LUTS. Study was concluded due to the location
and type of leiomyoma. Patients with intramural leiomy-
oma and anterior fibroids had worse symptoms of LUTS.
More prominent symptoms included: nocturia, urinary
urgency, frequency, and incontinence [54]. It can be con-
cluded that bladder compression due to anterior leiomyoma
resulted in LUTS (Fig. 1).
Vesicouterine fistula
A degenerating leiomyoma or leiomyosarcoma can cause a
fistula between the uterus and bladder, causing hematuria,
abdominal pain, and vaginal urine leakage [39]. Fistulas
may be confirmed with cystoscopy, cystogram methylene
blue test, or CT scan. Surgery is the preferred treatment,
utilizing omental flap interpositions in certain situations
[55].
Renal failure
If uterine leiomyomas are left untreated for prolonged
period of time, it could result in renal failure and renal
hypertension [56]. Leiomyoma may cause renal impair-
ment with good prognosis [57].
Hematuria
Hematuria may be a significant manifestation of leiomy-
oma, invading the bladder wall during degeneration, sarco-
matous changes, and vesico-uterine fistula [39, 58].
Fig. 1  Uterine leiomyoma, identified by the arrow, compressing and
adhering to the bladder presenting irritative and obstructive urinary
symptoms. This can interfere with storage and emptying of the blad-
der
Female sexual dysfunction
Masters and Johnson reported four stages of the female
sexual cycle which consisted of excitement, plateau,
orgasm, and resolution [59]. Female sexual response results
in increased pelvic blood flow, vaginal lubrication, and clit-
oral and labial engorgement. Increase in pelvic blood flow
is by hypogastric arterial bed [60].
Barriers to sexual function in female patients with leio-
myoma include pelvic pain, dyspareunia, orgasmic dis-
orders, decreased libido, decreased vaginal lubrication,
urinary incontinence, and obstructive and irritative blad-
der symptoms. Sexual dysfunction can occur secondary
to uterine leiomyomas when a large retroperitoneal mass
impinges upon the vagina. Repetitive contact can irritate
the lumen of the vagina, as projecting parietal peritoneum
cause pain and discomfort [61]. Currently, there is no treat-
ment for dyspareunia, which makes surgery an option.
Eight months are needed after surgery to resume normal
sexual intercourse [62]. Nerve sparing surgery of leiomyo-
mas may preserve sexual function in females [63].
Neurogenic bladder
Increased pressure within the bladder acts on the pro-
prioceptive sensory receptor signals onto the Barrington’s

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Int Urol Nephrol

Table 5  Non-urological complications of uterine leiomyomas nucleus (BN), within the brain. BN relays to the hypothal-
Non-urological complications amus and responding back to bladder to void. Both para-
sympathetic and sympathetic signaling aid in the contrac-
Cystic degeneration [65] tion of the bladder wall and relaxation of internal sphincter,
Torsion of uterine leiomyomas [40, 66] resulting in micturition [64]. Disruption of the pelvic auto-
Colorectal/anal difficulty [67] nomic pathways can result in neurogenic bladder and void-
Circulatory problems ing dysfunction. Leiomyoma can compress the bladder
 Deep-vein thrombosis [68, 69] and increase signaling of proprioceptive sensory receptors,
 Polycythemia [70] therefore causing increased frequency of micturition [44].
 Pelvic venous compression [71] Leiomyomas can also lead to urethral obstruction depend-
 Intravenous leiomyomatosis [25, 70] ing on the location of the growth [44].
 Thrombus extending into Right Heart [72]
 Thrombus extending into vena cava [73]
 Thrombophlebitis [74] Other complications of uterine leiomyomas
 Edema [75]
Leiomyomatosis peritonealis disseminata [76] Other, non-urological complications may present them-
Pregnancy complications selves due to uterine leiomyomas (Table 5).
 Miscarriage [29, 30]
 Prevention of implantation/infertility [77]
Uterine Prolapse [78] Treatment options
Anemia [79]
Pre-operative preparation for surgical management of com-
plicated uterine myomectomy or excision of leiomyoma
includes indwelling Foley catheter and insertion of ureteral
Table 6  Different treatment option for uterine leiomyomas stents to identify and prevent ureteral injury during com-
Treatment Options plicated surgery. Treatment options for management of
uterine leiomyomas range from observations and medical
Hormone therapy
management to invasive surgical options. The type of treat-
 Levonorgestrel-releasing intrauterine device [80]
ment used for a patient is dependent on several factors: age,
 Gonadotropin-releasing hormone agonist [81] health, symptoms, menopausal status, type of fibroids, if
 Progesterone-receptor modulators pregnant, and choice of future pregnancy (Table 6). Surgi-
  Mifepristone [82] cal controversies exist regarding best treatment options.
  Ulipristal acetate [83]
  Asoprisnil [84]
 Aromatase inhibitor Summary
  Letrozole [85]
Hifu of myoma [86] This paper examines the current literature of clinical mani-
Surgical procedures festations and impact of leiomyoma on urinary tract. Diag-
 Minimally invasive nostic and therapeutic options to relieve urologic symptoms
  Hysteroscopy [87] are discussed.
  Uterine artery embolization [88, 89]
  MRI-guided focused ultrasound surgery [90, 91] Acknowledgments  We gratefully acknowledge literature research
 Invasive assistance from Mrs. Wendy Isser and Ms. Grace Garey.
  Myomectomy
Author’s contributions  Gautam Dagur M.S. designed, organized,
   Open [92] and wrote the review article; corrected references; and solved queries
   Laparoscopy [93] related to scientific publications from the journals. Yiji Suh wrote the
   Robotic [94] review article and designed outline. Kelly Warren Ph.D. critiqued and
applied logical reasoning to the literature. Navjot Singh performed
  Hysterectomy [53, 95]
Medline searches, critiqued, and corrected the literature. John Fitzger-
Radiofrequency ablation [96] ald M.D. retrieved and evaluated scientific information related to
Guizhi Fuling Formula [26] the article. Sardar A. Khan M.D. FRCS FACS is the corresponding
author, formulated clinical concepts, reviewed the article, and cor-
rected the references.

13

Compliance with ethical standards  20. Temizkan O et al (2014) A case of parasitic myoma 4 years
Conflict of interest  The authors declare they have no conflict of
interest.
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