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-Adrenergic Antagonists in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Meta-Analysis of Randomized Controlled Trials
From the Department of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
| Correspondence to: Dr Qiang Dong, Department of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China (e-mail: dqiang{at}gmail.com). |
| Received for publication March 27, 2006; accepted for publication July 11, 2006. |
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Abstract |
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 Top Abstract Materials and MethodsResultsDiscussionReferences |
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-adrenergic antagonists on patients with
chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has not been
supported by well-evaluated study. The meta-analysis was performed to supply
the best evidence about use of this class of drugs in CP/CPPS. A fully
recursive literature search to June 2005 was conducted in PubMed, EMBASE, the
Cochrane Controlled Trials Register, and the Chinese Biomedicine Database to
identify potentially relevant randomized controlled trials. RevMan4.2 was used
for statistical analysis. Nine studies with 734 patients were included.
Combined analysis showed a significant reduction of total NIH-CPSI or I-PSS in
patients with treatment duration of more than 3 months. There were also
valuable results in urinary symptom alleviation. Alph-adrenergic
antagonists did not show benefit in pain. The meta-analysis revealed that the
use of -adrenergic antagonists was warranted in CP/CPPS, and the
treatment duration should be long enough (more than 3 months).
Key words: Evidence-based medicine, prostate, drug treatment
CP/CPPS is also refractory and puzzles urologists. Because the cause is
unknown at present, various empirical treatments are adopted in clinical
practice, such as -adrenergic antagonists, antibiotics, nonsteroidal
anti-inflammatory agents, finasteride, hyperthermia, and surgery
(Pontari, 2003;
El-Hakim, 2004). Nevertheless,
none of them are supported by credible evidence. Therefore, evidence-based
management is essential for both clinicians and patients. We evaluated all the
acquirable studies to try to supply the best evidence for the treatment of
CP/CPPS.
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Materials and Methods |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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Inclusion Criteria
The following are the criteria for the included studies. First, they should
be open or blind randomized studies. Second, patients should be diagnosed with
chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS), category III.
Chronic or acute bacterial prostatitis, acute urinary retention, urethral
stricture, benign enlargement, bacteriuria, prior prostate surgery, and cancer
were excluded. Third, patients randomly received -adrenergic
antagonists and placebo. The details of treatment methods should be described
and raw data was available in included studies.
Assessment of Methodological Quality
The assessment of methodological quality was undertaken by 2 of the authors
independently, and differences in assessment were solved by consensus. From
each study, data were extracted on the type of patients, the method of
treatment, and the effectiveness of treatment.
Jadad score and allocation concealment were adopted to evaluate the methodological quality of each trial (Moher et al, 1996): 0 for nonrandomized controlled trials, 1–2 for poor-quality trials, and 3–5 for high-quality trials. The concealment of allocation also was divided into 3 grades: A for adequate concealment, B for unclear concealment, C for inadequate concealment.
Statistical Methods
RevMan 4.2 software supplied by Cochrane Collaboration (Oxford, United
Kingdom) was used. The effect size of categorical variables was odds ratio
(OR) and 95% confidence intervals (CI) calculated from the raw data of the
selected studies. For numerical variables, if the unit was identical, weighed
mean difference (WMD) was used, and standardized mean difference (SMD) was
used when the unit was different. The homogeneity of adopted trials was tested
before meta-analysis. If the heterogeneity had no statistical significant
difference, a fixed-effects model was used during meta-analysis. Otherwise, a
random-effects model or subgroup analysis was adopted.
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Results |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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The Effects of -Adrenergic Antagonists
Nine studies compared the value of -adrenergic antagonists in
treatment of CP/CPPS with placebo; a total of 734 patients were randomly
assigned to receiving one kind of -adrenergic antagonists or placebo.
All studies were finished in the past 8 years. They were conducted in the
United States (Alexander et al,
2004), Canada (Nickel et al,
2004), Turkey (Gul et al,
2001; Evliyaoglu and Burgut,
2002), Finland (Mehik et al,
2003), Malaysia (Cheah et al,
2003), and China (Wang et al,
2002; Lu et al,
2004; Shen et al,
2004), respectively. Five studies are high-quality (Jadad score
3); none of them adopted intention-to-treat analysis. Criteria for
including or excluding in each study design were clear. The allocation
concealment in 1 study is adequate, but not mentioned in the others. The
duration of -adrenergic antagonist treatment varied from 4 weeks to 6
months. NIH-CPSI or I-PSS scores were adapted to evaluate the severity of
symptoms. Six articles supplied the NIH-CPSI or I-PSS scores before and after
treatment. Two supply the change of score before and after treatment. Three
did not supply the raw data in text, but the figures in 2 articles can be
measured for raw data. One study was excluded in meta-analysis for failure to
get the data (as shown in Figure
1 and Figure
2).
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-adrenergic
antagonists after being managed for more than 3 months; the combined SMD was
–2.00 (95% CI = –3.19 to –0.82). Meta-analysis of all 6
studies showed that the combined SMD was –1.73, favoring treatment (95%
CI = –2.52 to –0.94), but heterogeneity existed.
Figure 2 shows the outcome of 2 studies comparing the change of score before and after treatment. A total of 211 patients were included. There was heterogeneity, so SMD was adopted. The combined SMD was –4.16 (95% CI = –12.57 to 4.25).
Effect of -Adrenergic Antagonists on Pain
Four studies compared the effect of -adrenergic antagonists on pain
in patients with CP/CPPS. Meta-analysis of 3 studies including 183 cases
showed that the combined SMD was –2.44 (95% CI = –4.93 to 0.05)
(Figure 3).
|
-Adrenergic Antagonists on Urinary Symptoms-adrenergic antagonists on urinary symptoms of CP/CPPS. The combined
SMD was –1.60 (95% CI = –2.24 to –0.96)
(Figure 4).
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Effect of -Adrenergic Antagonists on Quality of Life
Three studies compared the effect of -adrenergic antagonists on
quality of life. Meta-analysis of 2 studies showed that the combined WMD was
–1.40 (95% CI = –1.47 to –1.33)
(Figure 5).
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Discussion |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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For this meta-analysis, a specific research question was defined, a
comprehensive literature search was conducted, and explicit criteria for study
selection and methodological quality assessment were used. In the overall
analysis, it was revealed that long-term use of -adrenergic receptor
blockers (more than 3 months) had an effect on improvement of symptoms in
patients with CP/CPPS, mainly in voiding symptoms. However, the conclusions
from overall analysis were weakened by the degree of heterogeneity of the
results.
Subgroup analyses were performed in an attempt to explain the heterogeneity
present and understand which subgroups might benefit the most. The most
prominent limitation in this meta-analysis was the different approaches used
in the raw data supplements, that is, mean score and change of score. The
results of studies had to be processed respectively according to the raw data
supplement when analyzing, rather than conducting an overall analysis.
Therefore, the value of conclusions was influenced.
Figure 1 shows the
-blockers can reduce the total score. Nevertheless, one study, the
Chronic Prostatitis Collaborative Research Network conducted by the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a
high-quality, multicenter, randomized, placebo-controlled trial, did not show
any benefit of -blockers in terms of total NIH-CPSI, pain score,
urinary score, or quality-of-life score. It is should be noted that treatment
duration of -blockers in this study conducted by NIDDK was only 6
weeks. Therefore, the treatment duration may be one important factor to
achieve satisfactory effectiveness. It is suggested that management with
-blockers in CP/CPPS should continue for not less than 3 months.
NIH-CPSI can be employed to evaluate the severity of CP/CPPS symptoms
quantitatively, and some authors have adopted I-PPS to evaluate them. They are
both excellent choices for evaluating the effectiveness of treatment. NIH-CPSI
evaluates the symptoms of CP/CPPS in 3 aspects, pain, urinary symptoms, and
quality-of-life; hence, the analysis is also conducted on the 3 aspects
respectively (Krieger et al,
1999). But I-PSS was designed for evaluation of benign prostatic
hypertrophy; it does not include the measurement of pain. A study conducted by
Evliyaoglu designed a pain questionnaire as well. Meta-analysis suggests that
there is no significant improvement in pain compared to placebo by treatment
of -adrenergic antagonists. The study conducted by NIDDK shares the
same conclusion. This may be attributed to the fact that the pain of CP/CPSS
was not only caused by the abnormal of smooth muscle tone within the prostate
gland and prostatic capsule and in the region of the bladder neck. Various
factors play a role in the mechanism of pain in CP/CPPS, such as inflammation
and other neuromuscular diseases. Further evaluation is needed in this
conclusion, because the other articles did not supply the details of NIH-CPSI
results.
Alph-adrenergic receptor blockers such as tamsulosin and terazosin
have been proved effective in treating voiding symptoms attributed to benign
prostatic hypertrophy (McConnell et al,
2003). These drugs are used empirically in patients with CP/CPPS
because such patients have similar voiding symptoms. The analysis showed that
-blockers may be helpful to the improvement of urinary symptoms in
patients with CP/CPPS. The conclusion supported the empirical use of
-blockers in CP/CPPS in practice. Although the data from the NIDDK
study do not support such results, the treatment duration in the NIDDK study
was only 6 weeks, so a longer treatment with -blockers may be warranted
in CP/CPPS. The pharmacologic effect of selective -blockers is to relax
the smooth muscle tone within the prostate gland and prostatic capsule and in
the region of the bladder neck in patients with benign prostatic hyperplasia,
which leads to the alleviation of obstructive and irritative voiding symptoms
of the lower urinary tract in men with benign prostatic hyperplasia; it may
also reduce voiding pressures and improve voiding flow dynamics in men with
CP/CPPS (Lowe, 2004). The
mechanism of -blockers in the treatment of CP/CPPS may be that they can
relax the neck of the urinary bladder and prostatic urethra, prevent the
reflux of urine, and improve the stability of the detrusor muscle.
According to the meta-analysis, -adrenergic antagonists are
warranted in treatment in patients with CP/CPPS. Longer duration of treatment
with -adrenergic antagonists may be beneficial. Alleviation of the
tension generated by edema of noninfectious inflammation through relaxation of
smooth muscles of the stroma may be speculated to contribute to the subjective
response of the prostatitis to -adrenergic receptor blockers
monotherapy. However, a number of factors are involved in the mechanisms of
the symptoms of CP/CPPS; therefore, more treatment strategies proved by
meta-analysis based on high-quality, randomized, controlled trials are
essential for CP/CPPS.
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  J. C. Nickel, J. N. Krieger, M. McNaughton-Collins, R. U. Anderson, M. Pontari, D. A. Shoskes, M. S. Litwin, R. B. Alexander, P. C. White, R. Berger, et al. Alfuzosin and Symptoms of Chronic Prostatitis-Chronic Pelvic Pain Syndrome N. Engl. J. Med., December 18, 2008; 359(25): 2663 - 2673. [Abstract] [Full Text] [PDF]
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