JOURNAL OF ENDOUROLOGY

Volume 28, Number 8, August 2014 Transurethral and Lower Tract Procedures
ª Mary Ann Liebert, Inc.
Pp. 962–968
DOI: 10.1089/end.2014.0090

Efficacy and Safety of Local Steroids for Urethra Strictures:

A Systematic Review and Meta-Analysis

Kaile Zhang, MD, Er Qi, MD, Yumeng Zhang, MD, Yinglong Sa, MD, PhD, and Qiang Fu, MD, PhD

Abstract
Introduction: Local steroids have been used as an adjuvant therapy to patients undergoing internal urethrotomy
(IU) in treating urethral strictures. Whether this technique is effective and safe is still controversial. The aim of
this study is to determine the efficacy and safety of local steroids as applied with the IU procedure.
Methods: A systematic review of the literature was performed by searching Medline, Embase, Cochrane
Library Databases, and the Web of Science. We included only prospective randomized, controlled trials that
compared the efficacy and safety between IU procedures with applied local steroids and those without.
Results: Eight studies were found eligible for further analysis. In total, 203 patients undergoing IU were treated
with steroid injection or catheter lubrication. Time to recurrence is statistically significant (mean: 10.14 and
5.07 months, P < 0.00001).The number of patients with recurrent stricture formation significantly decreased at
different follow-up time points (P = 0.05).No statistically significant differences were found between the re-
currence rates, adverse effects, and success rates of second IUs in patients with applied local steroids and those
without.
Conclusion: The use of local steroids with IU seems to prolong time to stricture recurrence but does not seem to
affect the high stricture recurrence rate following IU. When local steroids are applied with complementary
intention, the disease control outcomes are encouraging. Further robust comparative effectiveness studies are
now required.

Introduction suggest the need for the development of additional new

techniques and complementary strategies to prevent wound
U rethral stricture is one of the most common causes
of lower urinary tract symptoms among male patients.
The etiologies of this disease usually include perineal trauma,
contraction and recurrent stricture formation. The purpose of
the present meta-analysis is to identify and summarize the
evidence of the efficacy and safety of local steroids applied to
urethral catheterization, and chronic inflammatory diseases.1
patients with urethra stricture while undergoing IU.
The natural history of the disease often begins with a lesion of
the urethral mucosa and infection followed by scar formation.
Materials and Methods
As a result, scar tissue forms in the urothelium, which leads to
a decrease in the caliber of the urethral lumen. Eligibility criteria
Various techniques have been described for treatment of
The following eligibility criteria were used to identify
urethral strictures, depending on the stricture length, location,
relevant studies: (1) The target population was male indi-
and depth of the scar. Open urethroplasty of urethral stric-
viduals with urethra strictures undergoing IU with a cold
tures has been dramatically developed worldwide and re-
knife or laser. (2) The intervention involved local steroid
mains the gold standard for urethral reconstruction. This
application, either through injection or lubricated catheter, to
surgery is often carried out in high-volume, dedicated cen-
the fibrotic tissue of the stricture site (versus no steroid ap-
ters. Internal urethrotomy (IU), however, is still a worthwhile
plication). (3) The trial was a case-control study.
method for treating urethral strictures and is the first choice in
many secondary centers. According to the results of a na-
Information sources and selection of studies
tionwide survey, IU is used for most urethral strictures in the
United States.2 However, high recurrence rates have been We conducted our search in four databases: Pubmed
reported with this technique and its effectiveness is being (1950–February 2014), Embase (1974–February 2014), Web
questioned by many urologists.3 These low success rates of Science (1985–February 2014), and the Cochrane Library

Department of Urology, Sixth People’s Hospital, affiliated to Shanghai Jiaotong University, Shanghai, China.

962
EFFICACY AND SAFETY OF LOCAL STEROIDS FOR URETHRA STRICTURES 963

(including the Cochrane Central Register of Controlled

Trials, 1800–February 2014). Our searches used the terms
‘‘urethrotomy AND steroid,’’ ‘‘urethra AND steroid’’ and the
mesh words ‘‘steroids’’ AND ‘‘urethral Stricture/therapy.’’
No language restrictions were applied in the search strategy.
Two reviewers (K.L. Zhang and E. Qi) independently
searched the four databases. The search strategy found titles
and abstracts. Irrelevant and repeated titles and abstracts were
excluded. A consensus was obtained through discussion to
solve disagreements between the two reviewers.

Methodological quality assessment

Methodological quality was assessed by following the
guidelines of the Jadad criteria (maximum score 5).4 The
evaluation of the study’s quality was done independently by
two reviewers (K.L. Zhang and Y.M. Zhang). Randomiza-
tion, double-blind design, and description of dropouts of each
trial were assessed by the criteria. A trial with a score of 3 or
more is regarded as high quality. Each trial was given an
overall quality score, which was then used to rank the trials.

Data abstraction
All relevant data regarding patients’ interventions, char-
acteristics, and outcomes were extracted by using a stan-
dardized extraction form previously used by two reviewers
(K.L. Zhang and E. Qi). The outcomes of steroid use with IU
for urethra stricture contained the recurrence rate, the time to
recurrence, the adverse effects, and maximum flow rate
(Qmax) at each follow-up. Disagreement between the re-
viewers was resolved by discussion with senior investigators
(Q. Fu, and Y.L. Sa).

Quantitative data synthesis

Meta-analysis was done using Review Manager 5.2 soft-
ware (The Cochrane Collaboration, Oxford, UK). The
weighted mean differences (WMD) and odds ratio (OR) were FIG. 1. Flow chart depicting systematic incorporation of
used for the analysis of continuous and dichotomous vari- articles into the review.
ables, respectively. The confidence interval (CI) was estab-
lished at 95%. P values less than 0.05 were considered an
studies were included for quantitative synthesis and meta-
indication of statistical significance. The Cochran Q test was
analysis.5–9
used to assess the statistical heterogeneity among studies.
Statistical heterogeneity was assessed using I2 statistics: If
Study characteristics
the I2 value was less than 50%, the fixed effects of meta-
analysis were applied; if the I2 value was 50% or more, the Table 1 lists characteristics of the included studies. There
random effects of meta-analysis were used. The overall ef- were 469 participants in the eight studies; all of these patients
fects were tested by z test. Sensitivity analysis was used to were scheduled to receive IU and 203 of the patients were in
find out the statistical heterogeneity. experimental groups with local steroid treatment. The steroid
supplementations and procedures are described in Table 1. In
five studies, steroids were injected into the fibrotic tissue of
Results
the stricture site of patients after IU. In the other three studies,
Literature search and trial flow the catheters for dilatation were lubricated with steroid
ointment. The methodological quality scores of eight studies
We identified 1012 potentially relevant studies from the
are also displayed in Table 1. Scores lower than 3 indicate a
databases and obtained 49 full texts based on the title and
poorer quality of methodology. Disagreement between two
abstract reviews (Fig. 1.). During subsequent reviews of the
assessors was resolved by discussion with two senior authors
full texts, 10 studies were excluded for ‘‘laser versus cold
(Q. Fu, and Y.L. Sa).
knife,’’ 8 studies were excluded due to ‘‘dilation versus IU,’’
9 studies were excluded for contents about ‘‘IU and catheter
Recurrence rates
without steroid,’’ 3 studies were excluded because of sup-
plementation of other medications. Eleven remaining studies Recurrence rates were recorded in the follow-up period.
were excluded for not being controlled trials. Finally, 8 Eight studies with a total of 469 patients were eligible to
964 ZHANG ET AL.

Table 1. Characteristics of Eight Studies

Follow-up Jadad
Study Method Participants Length (mm) Site Intervention (month) score
Mazdak8 RCT 23 Steroid: 9.5 – 1.7 Bulbar Submucosal 24 4
(range: 6–15) triamcinolone
Control: 8.8 – 2.3 injection
(range: 5–15)
Hradec27 Retrospective 46 1–20 Multiple Submucosal 36 1
study triamcinolone
injection
Tavakkoli RCT 34 5–15 Bulbar, Submucosal 25 4
Tabassi6 penile triamcinolone
injection
Korhonen7 Case-control 17 5–30 Multiple Submucosal 12 1
study methylprednisolone
injection
Yesil28 RCT 22 < 15 Bulbar Catheter coated with 36 3
triamcinolone
Gucuk5 RCT 15 8.4 – 2.3 Bulbar Catheter coated with 18 4
triamcinolone
Hosseini9 RCT 30 Steroid: 8.5 – 4.0 Multiple Catheter coated with 12 4
(range: 3–15) triamcinolone
Control: 9.0 – 3.0
(range: 4–15)
Rivers21 Retrospective 16 — Multiple Submucosal 9–40 1
study fluorohydrocortisone
injection
RCT = randomized, controlled study.

FIG. 2. Comparison of recurrence rates between local steroid application and no steroid application. A square indicates
dichotomous outcomes, and the size of each square indicates the weight of each study. The diamond signifies that the mean
difference is in favor of the local steroid application group.
EFFICACY AND SAFETY OF LOCAL STEROIDS FOR URETHRA STRICTURES 965

FIG. 3. Comparison of time to recurrence between local steroid injection and no steroid use. SD = standard deviation.

measure the recurrence rate of IU with local steroid appli-
cation, as seen in Figure 2. Recurrence of urethra stricture
was defined by the need for a new procedure in the follow-up
period. We applied the fixed model because the quantity of I2
was less than 50%. The difference between recurrence rates
was not statistically significant between IUs with steroids and
IUs without steroids in each subgroup. The differences be-
tween subgroups of steroid injections with either Jadad
scores ‡3 (WMD = 0.53; 95% CI, 0.25–1.13, P = 0.10) or
those with Jadad scores <3 (WMD = 0.6; 95% CI, 0.27–1.35,
P = 0.22) were not significant. Similarly, there was no sta-
tistically significant difference in the subgroup with catheters
coated with the steroid lubrication (WMD = 0.51; 95% CI,
0.24–1.10, P = 0.09).
Time to recurrence
The time to recurrence after initial IU was analyzed in
three studies. In two studies of steroid injection (Fig. 3), the
time of recurrence was reported with continuous variable.
The months of recurrence of the steroid groups in two con-
tinuous variable studies were longer than the group without
local steroid use. The difference was statistically significant
(WMD = 4.43; 95% CI, 2.77–6.09, P < 0.00001). In the study
that used catheters, time was recorded with dichotomous
variable (Fig. 4); the number of patients with recurrence was
recorded and valued at three follow-up time points. The
differences between the patients with recurrence at the
follow-up time points were statistically significant (WMD =
0.29; 95% CI, 0.08–1.00, P = 0.05).
Adverse effects
Adverse effects of IU with local steroid application were
reported in three out of eight studies (Fig. 5) Of the 24 pa-
tients with recorded adverse effects, 10 contracted an infec-
tion, 6 experienced bleeding, and 8 had extravasation. The
adverse effects rate was similar between the patients treated
with steroids and those without steroids. There was no sta-
tistically significant different between the two groups’ total
number of adverse effects (WMD = 1.59; 95% CI, 0.71–3.58,
P = 0.26).
Qmax
In two studies, Qmax was recorded preoperatively and at
each follow-up (Fig. 6). The preoperative baseline of Qmax
was similar (P = 0.53), and all the Qmax time points between
the patients treated with steroids and those without steroids
was similar without statistically significant difference
(WMD = 0.11; 95% CI, 0.49–0.72, P = 0.71).
Discussion
Our meta-analysis of the currently available literatures
indicates that local steroid injection or lubrication could be a
safe adjuvant therapy. The outcomes showed that it could not
affect the recurrence rate and Qmax significantly; however, it
could significantly delay the time to recurrence in patients
undergoing IU for urethra stricture.
IU has gained an important place in the management of
urethral stricture since the 1980s.10 Although it has been
suggested as the procedure of choice for correction of ure-
thral strictures shorter than 1.5 cm, recurrence of strictures
has remained a major drawback.11 Pansadoro et al.12 reported
a curative success rate of 30% to 35%, and in 2010 Santucci
et al.13 published even worse success rates of less than 10%.
These low success rates suggest the need for the development
of adjuvant techniques to prevent wound contraction and thus
recurrent stricture formation. Even the use of techniques such

FIG. 4. Comparison of the number of recurrence at each follow-up time point between catheters coated with steroids and
no steroid use.
966
FIG. 5. Comparison of adverse effects between steroid injection and no steroid use.
as Foley catheter placement, self-catheterization, and the use
of urethral stents has unfortunately proven to be insufficient
in the long-term.5
Local steroid therapy for urethral strictures without IU
originated in 1965.14,15 In their 1976 retrospective study of
steroid management of urethral strictures, Sharp and Fin-
ney16 observed 96 patients for 1 year after urethral injection
with triamcinolone. The authors suggested that this treatment
was especially helpful in cases with strictures in the distal
urethra or the meatus. Uemura and colleagues17 reported
three cases of urethral stricture due to balanitis xerotica ob-
literans after hypospadias repair. They employed topical
steroid ointment or sublesional triamcinolone injection after
complete excision of the affected urethra and achieved sat-
isfactory outcomes. Garcia-Alix et al.18 reported three pa-
tients with severe hypospadias (scrotal and perineal) with
histories of multiple operations for that condition and post-
operative urethral stenosis at different sites. Enlargement was
performed using oral mucosa graft in two cases and a local
flap in the third. Urethral stricture recurred in all cases very
soon after surgery, and repeated dilations did not improve the
symptoms. Subsequently, the patients had repeated triam-
cinolone injections at hypertrophic scar and keloid sites in the
urethral lumen every 2 to 3 months. Follow-up ranged be-
tween 5 and 20 months, by the end of which all patients were
symptom free.
More researchers would like to combine injection of tri-
amcinolone or other steroids with IU. In their retrospective
study of patients from 1976 to 1978, Hradec and colleagues19
observed 149 patients with IU and followed up 1 to 3 years
postoperatively. In the series of patients treated by ure-
throtomy without corticoid injection, the rate of recurrent
stricture was 19.4%. Using a specially constructed needle for
injection of triamcinolone acetonide, the recurrence rate
ZHANG ET AL.
was reduced to 4.3%. Gaches et al.20 reported a multicenter
survey of 197 cases involving 322 urethrotomy procedures
from 5 urological departments in England. The authors re-
commended the additional injection of triamcinalone acetate
into the strictured area before urethrotomy in resistant cases.
Rivers and colleagues21 achieved less encouraging results,
however. In their study, the combination of IU with intrale-
sional corticosteroid injections resulted in a failure rate of
44%. Tavakkoli Tabassi et al.6 performed a double-blind,
randomized, placebo-controlled study on 70 patients with
urethral stricture. Complication and recurrence rates in the
experimental group were lower than the control group, but
the difference was not statistically significant. Whereas, time
to recurrence decreased significantly in the experimental
group. No complications could be attributed to the steroid
injections, so it seems that steroid injection is a safe method
and may delay the recurrence of urethral stricture. Korhonen
and associates7 treated one group in their study with IU and
intralesional methylprednisolone injections with a flexible
needle through the cystoscope. The total success rate was
only 11%, and 71% of patients in this group had to be treated
operatively for a recurrent stricture.
Gucuk and colleagues5 suggested using a catheter coated
with steroid to dilate the urethra instead of injection because
the effect of steroid injections is short and difficult to repeat.
Furthermore, injections themselves might contribute to scar
formation via the traumatic effect of the needle. Mazdak
et al.8 randomized 50 male patients with anterior urethral
stricture into 2 groups. The authors demonstrated that the
injection of triamcinolone significantly reduced stricture re-
currence after IU, with a mean follow-up of 13.5 ( – 5.5)
months postoperatively. In 2012, Kumar et al.22 evaluated the
outcome of IU with the holmium laser along with intrale-
sional triamcinolone injection in 50 patients. All patients
EFFICACY AND SAFETY OF LOCAL STEROIDS FOR URETHRA STRICTURES
FIG. 6. Comparison of Qmax between catheters coated with steroids and no steroid use. SD = standard deviation.
were followed up for 12 months postoperatively by history
and uroflowmetry. Twelve patients (24%) developed recur-
rent urethral strictures. The authors discovered that the suc-
cess rate in patients with strictures <1 cm in length was
95.8%. Kamp and colleagues23 used IU with a holmium:
YAG laser as a minimally invasive treatment for urethral
stricture in 32 male patients. Triamcinolone was instilled
intraurethrally after removal of the catheter. After a mean
follow-up of 27 months (range 13–38 months) 24 of the 32
patients were considered successful, although a urinary tract
infection was diagnosed in 5% of patients postoperatively.
Overall, the efficacy and safety of local steroid injection after
IU is still a controversial issue.
The present study demonstrated that no life-threatening
adverse effects occurred in patients undergoing IU with the
lubrication of steroid. The reported adverse effects in local
steroid injection included local infection, bleeding, and ex-
travasation. These were similar to the data of the placebo or
control group. This result suggested that these adverse effects
967
could be the result of the IU procedure instead of the steroid
supplementation. Augspurger et al.,24 however, reported two
cases of Cushing syndrome following intralesional triam-
cinolone acetonide injections of urethral strictures in chil-
dren. Graversen et al.25 reported that 11 out of 104 patients
(10.6%) experienced partial or total erectile dysfunction
following IU; most of these patients had distal and long
strictures. There was no report of sexual potency in the eight
studies included within our study.
The limitations of this meta-analysis include the small
number of participants in each study, which could be insuf-
ficient to achieve a conclusive result. There are also relevant
differences in the reviewed literature. For example, Gucuk5
discharged patients with the indwelling catheter within 2
weeks. Considering Albers’ paper,26 catheters should not be
left more than 3 days. Hosseini and colleagues9 included 35
patients after urethroplasty, but this is a completely different
situation than a primary urethral stricture that could influence
the outcome of IU. Tabassi6 had only a mean follow-up of
968
8.68 months, which seems to be not long enough given that
recurrence occurs within the first 12 months.
Conclusion
Altogether, IU does not appear to be an ideal treatment
option and should only be applied in selected cases with very
short strictures, no stricture recurrence, or older and unfit
patients. Steroid application might be considered in con-
junction with IU in order to prolong stricture recurrence.
Robust and well-designed randomized, controlled trials are
still warranted.
Disclosure Statement
No competing financial interests exist.
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Address correspondence to:
Qiang Fu, MD, PhD
Department of Urology
Sixth People’s Hospital affiliated
to Shanghai Jiaotong University
No. 600 Yishan Road
Xuhui District
Shanghai
China
E-mail: jamesqfu@aliyun.com
Abbreviations Used
CI ¼ confidence interval
IU ¼ internal urethrotomy
OR ¼ odds ratio
Qmax ¼ maximum flow rate
SD ¼ standard deviation
WMD ¼ weighted mean differences