25Archivio Italiano di Urologia e Andrologia 2018; 90, 1

ORIGINAL PAPER

Comparison of three most frequently used alpha blocker
agents in medical expulsive therapy for distal ureteral
calculi, result of a retrospective observational study 

Aykut Buğra Sentürk 1, Cemil Aydin 1, Musa Ekici 1, Muhammet Yaytokgil 2, Ali Akkoc 3, 
Mehmet Murat Baykam 1

1 Hitit University Corum Training and Research Hospital, Turkey;
2 Rize State Hospital, Turkey;
3 Alanya Alattin Keykubat University, Turkey.

Purpose: In this  study, we compared the
effects of three agents frequently used in

daily life for medical expulsive therapy.
Materials and methods: A total of 143 patients meeting the cri-
teria were included in the study. Patients were divided into
three homogeneous drug groups which were tamsulosin group
(n:48), alfuzosin group (n:47) and silodosin group (n:48). 
The time of stone expulsion, analgesic needs, side effects of the
medicine and endoscopic intervention needs of the patients
were recorded.
Results: The rate of stone expulsion was 70.8% (n:34) in tamsu-
losin group, 70.2% (n:33) in alfuzosin group, and 75% (n:36) in
silodosin group. No significant difference was observed among
the rates of stone expulsion in three groups, and the rates of
stone expulsion were similar (p = 0.778). The duration of stone
expulsion was significantly different in the groups (p = 0.012):
the time of stone expulsion for tamsulosin was 2.33 ± 0.78 days
longer than for Silodosin, indicating a significant difference.
There was no significant difference between tamsulosin-alfu-
zosin and silodosin-alfuzosin (respectively p = 0.147, 
p = 0.925).
Conclusions: The results of this study showed that medical
expulsive therapy by using alpha blocker agents is safe and
efficacious. This option must be kept in mind for patients who
do not ask for surgery as the first-step treatment for eligible
patients.

KEY WORDS: Urology; Ureter; Stone.

Submitted 13 February 2018; 24 February 2018

Summary

No conflict of interest declared.

expulsive therapy, extracorporeal shock wave and lithotrip-
sy (ESWL), retrograde ureterorenoscopy, antegrade per-
cutaneous ureterorenoscopy, and laparoscopic and open
ureterolithotomy (3).
The location and the size of the stone, the availability of
the technology, the treatment cost, the experience of the
surgeon, and the preference of the patients are consid-
ered when a treatment is chosen among the other alter-
natives (4).
The probability of spontaneous expulsion of the ureteral
calculi has two factors: the size of the calculi and the
anatomic location of the calculi. According to a meta-
analysis, the rate of spontaneous expulsion of the stones
smaller than 5 mm is 68% while it is 47% for the stones
bigger than 5 mm and smaller than 10 mm (5). When
anatomic location is considered, it is seen that 71% of the
distal ureteral calculi and 22% of the proximal ureteral cal-
culi expulse spontaneously (6). Therefore, spontaneous
expulsion of the stone protects the patient from surgical
intervention, anesthesia risk and additional costs, who
does not have infection history and who has pain control
and small size of calculi. By this way, with the under-
standing of the ureter physiology in detail, the concept of
medical expulsive therapy has been developed in order to
make the spontaneous expulsion of the stone easier. 
The purpose of the medical expulsive therapy is to
increase the spontaneous probability of the stone expul-
sion by enabling relaxation in the ureter smooth muscle
structure and eventually it reduces the pain level and fre-
quency felt by the patient, shorten the time of stone
expulsion, reduces the need of operation, prevents the
risk and complications related with the operation and
reduces the cost of the treatment. Some main points
need attention during the medical expulsive treatment.
The most important two factors of them are the location
of the calculi in the ureter and the size of the calculi. The
maximum upper limit recommended for the treatment of
the medical expulsive is 10 mm (7).
Many treatment alternatives are available for medical
expulsive treatment. Calcium channel blockers, alpha
blockers, phosphodiesterase type 5 inhibitors and corti-
costeroids are the most frequently used drugs. In the
guide of European Society of Urology, it is mentioned that

DOI: 10.4081/aiua.2018.1.25

INTRODUCTION
Urolithiasis is one of the most common disorders of uri-
nary tract affecting about 5%-10% of the population.
Renal stones are most prevalent between the ages of 20
and 40 years and are three times greater in men than
women (1). Women typically excrete more citrate and
less calcium than men, which may explain the higher
incidence of stone diseases in men. Twenty-two percent
of all urinary tract stones are found in ureter, of which
68% are seen in the distal ureter (2).
The treatment of urinary stones basically varies depend-
ing on the anatomic location of the stone, the size of the
stone and the factors related with the patient. The treat-
ments of the ureteral calculi are observation, medical

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Archivio Italiano di Urologia e Andrologia 2018; 90, 1

A. Buğra Sentürk, C. Aydin, M. Ekici, M. Yaytokgil, A. Akkoc, M. Murat Baykam

26

alpha blockers are more successful for medical expulsive
treatment and calcium channel blockers are successful
only when nifedipine is used for medical expulsive treat-
ment. Also corticosteroids are recommended to be used
not alone but with other drugs for medical expulsive
treatment purpose (8).
In the various studies, it was shown that phosphodiesterase
type 5 inhibitors increase the spontaneous stone expulsion
by causing the relaxation of ureter smooth muscles; how-
ever, there is no sufficient data for its clinical use (9).
Although alpha adrenergic receptors are available in all
ureter segments, these receptors are usually located at
distal ureter (10). Density order in distal ureter is alpha-
1d> alpha-1a>alpha-1b (11).
In this retrospective study, we investigated the effects of
three agents frequently used in daily life for medical
expulsive therapy on each other.

MATERIALS AND METHODS
The study was undertaken retrospectively in accordance
with the principles of the Declaration of Helsinki.
Between January 2013 and October 2017, the data of
365 patients who were admitted to a polyclinic with dis-
tal ureter calculi size between 4-10 mm were investigat-
ed retrospectively. 
They were grouped homogeneously in terms of calculi
size, patient age and gender. Those patients who had
bilateral ureter calculi, severe urinary tract infection,
severe colic attack, fever, severe hydronephrosis, renal
impairment, history of endoscopic surgery due to ureter
calculi, and history of drug which interact with alpha
blockers were excluded from the study. Urine analysis,
blood urea and creatinine values and complete blood
count of all the patients were recorded before the treat-
ment. Those patients who had calculi with the size of 4-
10 mm which were located under the common iliac
arteries and confirmed by computarized tomography,
and those responding to the analgesic treatment were
included in the study. A total of 143 patients meeting the
criteria were included in the study. Patients were divided
into three homogeneous drug groups which were tamsu-
losin group (n:48), alfuzosin group (n:47) and silodosin
group (n:48).
The patients in tamsulosin group received one dose of 0.4
mg/day tamsulosin orally, the patients in alfuzosin group
received one dose of 10 mg/day alfuzosin orally, and those
in silodosin group received one dose of 8 mg/day silodosin
orally. In each group, the medical treatment was main-
tained until the patients expulsed the stone or for four
weeks. When the patients had pain, they were adminis-
tered analgesic. 
The time of stone expulsion, analgesic
needs, side effects of the drug and endo-
scopic intervention needs of the patients
were recorded. The expulsion of the
non-transparent stones was confirmed
by ultrasonography and transparent
stones were confirmed by unenhanced
tomography. 
All statistical analysis were performed
with SPSS statistical software (Version

22.0, SPSS Inc., Chicago, IL, USA). Descriptive statistics
were presented as mean ± standard deviation (SD) values.
Shapiro-Wilk test was used to check for normality of dis-
tribution. Patient characteristics in the three age groups
were compared using Pearson's chi-squared test in case
of discrete variables. 
The significance of the difference between three groups
were assessed by using one-way analysis of variance
(ANOVA) in case of normal data distribution, or Kruskal-
Wallis test (non-parametric analysis of variance) in case
of non-normal distribution for continuous variables.
Bonferroni post hoc test was applied to determine the
differences between the pairwise groups. P values < 0.05
were considered to be statistically significant. 

RESULTS
In each group, the sizes of the stones were similar (p =
0.224) (Table 1). 
The sizes of the stones were 7.10 ± 1.80 mm in tamsu-
losin group, 6.55 ± 1.58 mm in alfuzosin group, and
6.65 ± 1.57 mm in silodosin group. 
The rate of stone expulsion was 70.8% (n:34) in tamsu-
losin group, 70.2% (n:33) in alfuzosin group, and 75%
(n:36) in silodosin group. No significant difference was
observed among the rates of stone expulsion in the three
groups, and the rates of stone expulsion were similar
(p = 0.778). Despite the medical expulsive treatment last-
ing for four weeks, the rates of ureterorenoscopy opera-
tions due to non-expulsing stone was 29.2% (n:14) in
tamsulosin group, 10.6% (n:14) in alfuzosin group and
25% (n:12) in silodosin group. 
The duration of stone expulsion was 10.41 ± 3.61 days
in tamsulosin group, 8.87 ± 3.54 days in alfuzosin
group, and 8.09 ± 3.66 days in silodosin group. 
The duration of stone expulsion was significantly differ-
ent in the groups (p = 0.012). According to post hoc test
results, the difference between silodosin and tamsulosin
groups was (p = 0.010). So, the time of stone expulsion
in tamsulosin was 2.33 ± 0.78 days longer than the one
in silodosin, indicating a significant difference. 
There was no significant difference between tamsulosin-
alfuzosin and silodosin-alfuzosin (respectively p = 0.147,
p = 0.925).
No statistical difference was found between 3 drug groups
in terms of frequency of colic attack and analgesic usage
(respectively p = 0.25, p = 0.45). Hypotension which is a
major adverse effect of the drug was 8.5% in tamsulosin
group, 4.5% in silodosin group, and 6.4% in alfuzosin
group. Although retrograde ejaculation was seen more fre-
quently in silodosin group than the other groups, there
was no statistical difference (p = 0.35).

Table 1. 
Demographic values of groups.

Tamsulosin Alfuzosin Silodosin P value

Mean age ± SD (year) 40.37 ± 12.43 41.15 ± 12.15 41.46 ± 15.04 p = 0.919

Mean stone diameter ± SD (mm) 7.10 ± 1.80 6.55 ± 1.58 6.65 ± 1.57 p = 0.224

Male/female (n) 24/24 27/20 26/22 p = 0.778

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DISCUSSION
Due to risk of complications for ureteral stones less than
10 mm in size during minimal invasive treatments and
their high costs, nowadays the treatment of ureteral
stones vary in the direction of conservative treatment.
Management of ureteral stones depends on the size, loca-
tion, number, structure of the stone and presence of the
symptoms. Ureteral spasm, ureteral anatomy and mucos-
al edema by inflammation affect the rate of stone expul-
sion. Watchful waiting for distal ureteral stones is a good
option in patients with no infection, tolerable colic
attacks and small stone size. The aim of medical expul-
sive therapy is to facilitate spontaneous stone expulsion
by relaxing ureteral smooth muscle without any disrup-
tion of ureteral peristalsis and to reduce the severity of
pain of the patient.
This idea depends on good spontaneous expulsion rates
of small ureteral stones. Natural spontaneous expulsion
rate of distal ureteric calculi is 68% for stones less than 5
mm in size. And this rate is about 47% for stones with
sizes between 5 and 10 mm (5). Besides of the size, the
localization of the calculi is also an important factor for
spontaneous expulsion. The spontaneous expulsion rate
of proximal ureter stone is 21%, of middle ureter stone
46%, and of distal ureteral stone 71% (6).
Alpha-1 receptors have been classified into three subtypes,
which are alpha-1A, alpha-1B and alpha-1D. Alpha-1D
and alpha-1A are the most common adrenoceptors found
in the ureter (12) and the distributions of these receptors
are alpha-1D > alpha-1A > alpha-1B (11). Alpha-1D
receptors are found predominantly in the intramural
ureter and detrusor muscle and they are the target of med-
ical expulsive therapy as they are found generally in the
distal ureter (13). Itoh et al. reported that the distal part of
the ureter expresses the higher amount of alpha-1 adreno-
ceptor than the other parts. Also it was demonstrated that
alpha-1D adrenoceptor mRNA is much more common
than alpha-1A adrenoceptor mRNA in each part of the
ureter. Therefore, alpha-1D adrenoceptor blocker can be
more useful than alpha 1A adrenoceptor blocker to facili-
tate expulsion of ureteral calculi according to their study
(11). But in contrast, Tatemichi et al. reported that ureteral
motility is medicated more commonly by alpha 1A
adrenoceptors (14).

A study comparing the efficacy of silodosin to
tamsulosin including 136 patients with proxi-
mal ureter stone which are in diameter of 4-10
mm showed that the patients treated with silo-
dosin demonstrated a significant increase in
expulsion rate and a decrease in expulsion
duration of lower ureteral stones (61.2 versus
80.3%) (19). A meta-analysis involving eight
publications from Huang W et al. indicated that
silodosin was superior to placebo or tamsu-
losin in the efficacy for distal ureteral calculi
treatment with better control of pain (18).
Also, a multi-institutional, randomized, dou-
ble-blinded, placebo-controlled trial from Sur
RL et al. reported that silodosin was found to
be well tolerated and beneficial in facilitating
the expulsion of distal ureteral stones (17). 
In our study, we found a similar effect between

silodosin and tamsulosin groups in terms of stone expul-
sion (p = 0.010). Stone expulsion duration was 10.41 +
3.61 days in tamsulosin group and 8.09 + 3.66 days in silo-
dosin group. The stone expulsion duration of tamsulosin
was significantly longer than the duration with silodosin
(2.33 ± 0.78 days). As mentioned in similar studies, we
consider that this finding is associated with the selective
alpha 1-A adenoceptor antagonist effect of silodosin rather
than the alpha-1 adrenoceptor antagonist effect of tamsu-
losin. We also did not found any statistical difference
between tamsulosin-alfuzosin and silodosin-alfuzosin in
terms stone expulsion duration (p = 0.147, p = 0.925
respectively).
In the study of Imperatore V et al., it was reported that
both tamsulosin and silodosin are equally effective as
medical expulsive treatment (MET) for distal ureteral cal-
culi sized < 10 mm. Stone-expulsion rate was 88% in
silodosin group and 82% in tamsulosin group (20).
Similarly, while stone expulsion rate was 70.8% in tam-
sulosin group, 70.2% in alfuzosin group and 75% in silo-
dosin group in our study, we found no statistical differ-
ence between three groups in terms of stone expulsion
rates (p = 0.778). 
Increase in intraureteral pressure due to obstruction causes
colic pain attacks. Alpha blockers which are used predom-
inantly for stone expulsion may also decrease analgesic
drug usage by expulsion of ureteral calculi (16). Kumar et
al. reported that stone expulsion by an alpha 1 adrenocep-
tor on the obstructed ureter is facilitated by increasing the
intaureteral pressure gradient around the stone and
decreasing peristalsis below the ureter (13) and alpha
blockade may decrease ureteric colic attacks by blocking
C fibers which are responsible for pain (15).
Although we could not find any statistical difference
between three groups in terms of the frequency of colic
attack in our study (p = 0.45). The medical expulsive
treatment should be discontinued in case of severe uri-
nary infection and hydronephrosis, and endoscopic sur-
gery should be considered. In our study, the rate of
patients who needed endoscopic procedure due to non-
expulsing stones was 29.2% (n:14) in tamsulosin group,
10.6% (n:14) in alfuzosin group, and 25% (n:12) in silo-
dosin group. Medical expulsive therapy is a cost-effective
non-surgical treatment for ureteral calculi less than 10

27Archivio Italiano di Urologia e Andrologia 2018; 90, 1

Alpha blockers in medical expulsive therapy

Figure 1. 
Stone expulsion duration in the groups.

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Archivio Italiano di Urologia e Andrologia 2018; 90, 1

A. Buğra Sentürk, C. Aydin, M. Ekici, M. Yaytokgil, A. Akkoc, M. Murat Baykam

28

mm in size. Several studies showed that alpha-1 adreno-
ceptor blockers can facilitate spontaneous passage of dis-
tal ureteral calculi with minimal side effects. A study
from Bensalah K et al. reported that medical expulsive
therapy using tamsulosin resulted in a cost advantage for
1,132 USD over observation in USA. Since the cost of
tamsulosin is only 2.08 USD per day whereas the esti-
mated cost of ureteroscopy is 4973 USD in USA (4).
According to a systematic review and meta-analysis based
on 21 studies, of which the main topic was to understand
the effect of medical expulsive treatment (MET) of ureter
stone, by Picozzi SC et al., it was reported that medical
expulsive therapy should be offered to patients who are
complaining about distal ureteral calculi (21).
Our study have some limitations. One of them is that we
do not have a control group since the main objective of
the study was to compare the effects of these three dif-
ferent type of alpha blockers. Other limitation was the
small number of the samples. However, the results of the
power analysis during the design of the study showed
that current numbers were not statistically problematic.

CONCLUSION
No significant difference was found between the three
groups in terms of the rate of stone expulsion (p =
0.778). However, the duration of stone expulsion had a
significant difference among the groups (p = 0.012).
Stone expulsion duration for tamsulosin was 2.33 ± 0.78
days longer than for silodosin, which is a considerable
difference (p = 0.010). There was no significant differ-
ence between tamsulusin-alfuzosin and silodosin-alfu-
zosin (p = 0.147 and p = 0.925, respectively). The results
of this study showed that medical expulsive therapy by
using alpha blocker agents are safe and efficacious. 
This option must be kept in mind who do not ask for
surgery as the first-step treatment for eligible patients.

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Correspondence
Aykut Buğra Sentürk, MD (Corresponding Author)
aykutbugra@gmail.com
Cemil Aydin, MD
cemilaydin78@yahoo.com.tr
Musa Ekici, MD
musaekici40@gmail.com
Hitit University Corum Training and Research Hospital, Turkey

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