Therapeutic effect of α-blockers and antimuscarinics in male lower urinary tract symptoms based on the International Prostate Symptom Score subscore ratio.
ABSTRACT To investigate if the International Prostate Symptom Score (IPSS) voiding-to-storage subscore ratio (IPSS-V/S) can help to guide the treatment for male lower urinary tract symptoms (LUTS).
Men aged 40 years or older with a total IPSS (IPSS-T) 8 or more were constitutively enrolled from January 2010 to December 2010. The IPSS voiding (IPSS-V) and storage subscore (IPSS-S) were recorded separately, and the IPSS-V/S was calculated. Patients were divided into two groups according to the baseline IPSS-V/S value. First-line doxazosin (4 mg per day) and tolterodine (4 mg per day) monotherapy were given to patients with IPSS-V/S > 1 and IPSS-V/S ≤ 1, respectively. The IPSS-T, IPSS-V, IPSS-S, quality of life (QoL), maximum flow rate (Qmax), voided volume and postvoid residual (PVR) were measured at 1 month (visit 1) and 3 months (visit 2) after treatment.
After medical treatment for 1 month, 89/116 (76.7%) patients receiving tolterodine and 218/279 (78.1%) patients receiving doxazosin reported an improved outcome (global response assessment, GRA ≥ 1 point). The mean IPSS-T, IPSS-S decreased, and QoL improved significantly in both groups. Significant increased Qmax, voided volume, decreased IPSS-V and PVR were noted only in patients receiving doxazosin. There was no significant increase of PVR (from 50.1 to 60.4 ml, p = 0.106), and no patient developed urinary retention after tolterodinie monotherapy for 1 month. However, patients aged more than 70 years had significant association with increased PVR (≥ 50 ml).
Initial treatment with doxazosin for patients with IPSS-V/S > 1 and tolterodine for patients with IPSS-V/S ≤ 1 is safe and feasible. Elderly people (≥ 70 years) and patients with Qmax < 10 ml/s are more likely to have increased PVR (≥ 50 ml).
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ABSTRACT: Chronic inflammation is considered as one of the contributing mechanisms of lower urinary tract symptoms (LUTS). Serum C-reactive protein (CRP) level is the widely used biomarker of inflammatory status. This study investigated the association between serum CRP level in men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) before and after medical treatment. A total of 853 men with BPH and LUTS were enrolled. All patients completed the International Prostate Symptoms Score (IPSS) questionnaire and urological examinations. The parameters of uroflowmetry (maximum flow rate, Qmax; voided volume, VV), post-void residual (PVR), total prostate volume (TPV) and transition zone index (TZI), serum prostate specific antigen (PSA), and serum CRP levels were obtained. All patients were treated with alpha-blocker or antimuscarinic agent based on the IPSS voiding to storage subscore ratio (IPSS-V/S). Correlation analyses were performed between serum CRP levels with age, IPSS, TPV, TZI, Qmax, PVR, VV, PSA and between baseline and post treatment. The mean age was 66.9±11.6 years old and the mean serum CRP levels were 0.31±0.43 mg/dL. Univariate analyses revealed serum CRP levels were significantly associated with age (p<0.001), PSA levels (p = 0.005) and VV (p = 0.017), but not significantly associated with TPV (p = 0.854) or PVR (p = 0.068). CRP levels were positively associated with urgency (p<0.001) and nocturia (p<0.001) subscore of IPSS, total IPSS (p = 0.008) and storage IPSS (p<0.001) and negatively associated with IPSS- V/S ratio (p = 0.014). Multivariate analyses revealed that serum CRP levels were significantly associated with age (p = 0.004) and storage IPSS subscore p<0.001). Patients with IPSS-V/S<1 and treated with tolterodine for 3 months had significant decrease of CRP levels after treatment. Serum CRP levels are associated with storage LUTS and sensory bladder disorders, suggesting chronic inflammation might play a role in the patients with storage predominant LUTS.PLoS ONE 01/2014; 9(1):e85588. · 3.53 Impact Factor
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ABSTRACT: Differentiation of different lower urinary tract dysfunctions (LUTD) is essential for selecting the optimal first-line medical treatment of lower urinary tract symptoms (LUTS). This study analysed the association of the severity of LUTS with LUTD and therapeutic results based on the International Prostate Symptom Score (IPSS) voiding to storage (V/S) ratio. Lower urinary tract symptoms were evaluated in 849 men using the IPSS questionnaire and the IPSS-V/S ratio. The prostate measures, urinary flow measures, and C-reactive protein (CRP) were investigated at baseline and 1 month after treatment. Therapeutic results were assessed by changes in the quality of life index (QoL-I). The associations of the severity of LUTS with LUTD and therapeutic results were analysed. Mild (IPSS ≤ 7), moderate (8 ≤ IPSS ≤ 19) and severe LUTS (IPSS ≥ 20) were noted in 215, 461 and 173 men. IPSS-V/S ≤ 1 was noted in 81.4% of patients with mild LUTS, while IPSS-V/S > 1 was noted in 71.1% of patients with severe LUTS. After treatment with alpha-blockers in patients with IPSS-V/S > 1 and antimuscarinic agents in patients with IPSS-V/S ≤ 1 for 1 month, 84.0% and 88.8% of patients with mild LUTS had effective therapeutic results, respectively. In contrast, the therapeutic results were less effective in patients with moderate (64.9% and 63.8%, respectively) or severe LUTS (50% and 33.3%, respectively). Patients with benign prostatic hyperplasia (BPH) and mild LUTS have more bladder storage dysfunction, whereas patients with BPH and severe LUTS had higher grade of bladder outlet disorders in associated with storage symptoms. Treatment based on the IPSS-V/S ratio results in good therapeutic results in men with mild and moderate LUTS, but not in men with severe LUTS.International Journal of Clinical Practice 01/2014; · 2.54 Impact Factor
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ABSTRACT: To summarize data concerning the medical treatment of men with overactive bladder symptoms published in peer-reviewed journals between January 2012 and March 2013. Results of large, randomized trials of solifenacin in combination with tamsulosin in men with lower urinary tract symptoms, including voiding and storage ones, have dominated the medical literature on the subject for the past 12-16 months. Solifenacin in upfront combination with alpha-blockers or as add-on therapy in men with residual storage symptoms despite alpha-blockade offers additional benefits in symptom control. In accordance with data from previous studies on other antimuscarinics, improvements are significant only for some of the efficacy outcomes. Solifenacin in combination with alpha-blockers is associated with an increase in postvoid residual urine volume but not a significantly increased risk of retention. Recent data also indicate that the combination of antimuscarinics with alpha-blockers is cost-effective with long-term efficacy and safety. Recent evidence further supports the efficacy and safety of antimuscarinics in combination with alpha-blockers in treating storage symptoms in men with lower urinary tract symptoms. More studies are needed to evaluate criteria for selecting men likely to benefit more from antimuscarinics and investigate other overactive bladder treatments in male populations.Current opinion in urology 07/2013; · 2.12 Impact Factor
Therapeutic Effect of α-blockers and Antimuscarinics in Male
Lower Urinary Tract Symptoms based on International Prostate
Symptom Score (IPSS) Subscore Ratio
Chun-Hou Liao1,Shiu-Dong Chung2, Chia Hsiang Lin3, Hann-Chorng Kuo4
1 Department of Urology, Cardinal Tien Hospital and Fu-Jen Catholic University, Taipei, Taiwan; 2Department of Urology, Far Eastern Memorial Hospital, Taipei, Taiwan; 3
Department of Urology, E-Da Hospital, Kaohsiung City, Taiwan;4Department Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
Total (N=395)IPSS-V/S>1 (N=279) IPSS-V/S<=1 (N=116) P value
Age (years)66.4± ±10.8 65.6± ±10.5 68.4± ±11.3 0.017
IPSS-T17.1± ±6.3418.0± ±6.4714.8± ±5.400.000
IPSS-V10.3± ±5.2312.3± ±4.375.31± ±3.51 0.000
IPSS-S6.82± ±3.535.70± ±3.099.51± ±3.050.000
QoL3.89± ±0.883.88± ±0.82 3.91± ±1.01 0.835
TPV (ml)39.2± ±19.9 38.9± ±18.339.9± ±23.3 0.672
TZI 0.34± ±0.140.34± ±0.14 0.33± ±0.13 0.921
PSA (ng/ml) 2.45± ±2.34 2.37± ±2.272.65± ±2.490.270
Qmax (ml/s)12.0± ±6.79 11.4± ±6.0213.3± ±8.210.027
Volume (ml) 234.5± ±156.4 242.7± ±150.1 214.8± ±169.6 0.114
Table 3. Comparisons of baseline parameters between GRA >=1 and GRA<1 at 1 month
52.7± ±59.054.1± ±57.949.4± ±61.6 0.471
Pre-TxPost-Tx P-value Pre-TxPost-TxP-value
IPSS-T18.0± ±6.4710.8± ±6.36 0.00014.8± ±5.4011.2± ±6.810.000
IPSS-V12.3± ±4.376.49± ±4.970.0005.31± ±3.514.84± ±4.750.272
IPSS-S5.70± ±3.094.31± ±2.800.0009.51± ±3.056.40± ±3.470.000
Qmax11.4± ±5.9513.6± ±6.630.000 13.1± ±8.1013.6± ±7.90 0.357
Volume 244.0± ±148.3268.3± ±150.70.004 212.5± ±168.8231.6± ±163.60.056
PVR53.9± ±58.742.9± ±49.3 0.00250.1± ±62.660.4± ±60.40.106
QoL3.88± ±0.82 2.82± ±0.960.000 3.91± ±1.012.82± ±1.18 0.000
Age65.9± ±10.664.5± ±10.2 0.35368.8± ±11.367.3± ±11.1 0.555
IPSS-T 17.9± ±6.5118.4± ±6.360.62814.9± ±5.4914.6± ±5.220.774
IPSS-V12.3± ±4.40 12.6± ±4.300.6415.40± ±3.59 5.00± ±3.270.602
IPSS-S5.66± ±3.095.82± ±3.13 0.7239.49± ±3.13 9.56± ±2.810.928
TPV40.0± ±18.4 35.0± ±17.70.06239.8± ±24.239.9± ±20.5 0.986
TZI0.35± ±0.140.30± ±0.130.0370.34± ±0.130.31± ±0.140.226
Qmax 11.4± ±6.1411.5± ±5.610.88014.0± ±8.7511.1± ±5.670.046
Volume 238.9± ±140.7256.6± ±181.60.499217.2± ±167.9207.1± ±178.10.791
PVR 56.4± ±59.545.7± ±51.20.21549.6± ±60.148.6± ±67.60.943
Antimuscarinics, alone or in combination with α-blockers, appear to be effective and safe for male storage LUTS in men without elevated postvoid residual (PVR) [1-3]. Total prostate volume
(TPV), serum prostate specific antigen (PSA) level, maximum flow rate (Qmax), and PVR were commonly used parameters to guide the initial treatment choice for male LUTS [2-3]. But the definite
cut-off values of these parameters avoiding first-line antimuscarinics therapy are still controversial. In addition, determining the presence and the degree of BOO is occasionally difficult for primary
care physicians (PCPs), especially for non-urologists without urological diagnostic equipment for uroflowmetry, bladder scanning, or transrectal ultrasound.
We had reported that measuring International Prostate Symptom Score (IPSS) subscores and calculating the IPSS voiding to storage subscore ratio (IPSS-V/S) is a simple and useful method to
differentiate failure to voiding and failure to storage lower urinary tract dysfunction . Failure to voiding dysfunction was found in 81.2% of patients with IPSS-V/S >1, while failure to storage
dysfunction was found in 75.7% of patients with IPSS-V/S<=1. To further investigate if IPSS-V/S can be used to help guiding the initial treatment of male LUTS, we conduct a prospective open-
labeled study using first-line α-blockers for men with IPSS-V/S>1 and antimuscarinics monotherapy for those with IPSS-V/S<=1, regardless of their TPV, serum PSA levels, PVR, or Qmax.
• Materials and Methods
Men aged 40 years or older with a total IPSS (IPSS-T) 8 or more were constitutively enrolled from January 2010 to December 2010. The IPSS voiding (IPSS-V) and storage subscore (IPSS-S)
were recorded separately, and the IPSS-V/S was calculated. Baseline TPV, transition zone index (TZI), Qmax, PVR, voided volume, serum PSA levels, and quality of life (QoL) index were obtained.
Men with documented genitourinary cancer, acute or chronic urinary retention, diabetes mellitus, frank neuropathy, urinary tract infection, previous urethral surgeries, abnormal findings on digital
rectal examination or elevated serum PSA levels (>= 10 ng/ml) were excluded. Patients were divided into 2 groups according to baseline IPSS-V/S value. First-line doxazosin 4mg and tolterodine
4mg per day monotherapy were given to patients with IPSS-V/S>1 and IPSS-E/S<=1, respectively, regardless of their TPV, TZI, Qmax, PVR, or serum PSA levels. The IPSS-T, IPSS-V, IPSS-S,
QoL, Qmax, voided volume, and PVR were measured at 1 month (visit 1) and 3 months (visit 2) after treatment. Patients rated their symptoms after treatment compared to baseline using a
validated global response assessment (GRA), a 7-point scale ranging from markedly worse (−3) to markedly improved (+3). Combination therapy with α-blockers and antimuscarinics was
prescribed for those with GRA<1 at 1 month after treatment based on investigator’s choice.
Table 1 showed the baseline parameters and comparisons between men with IPSS-V/S>1 and IPSS-V/S <=1. IPSS-T and IPSS-V were significantly higher in patients with IPSS-V/S>1, while
IPSS-S was significantly greater in those with IPSS-V/S<=1 (p<0.001). Patients with IPSS-V/S<=1 had higher Qmax (p=0.027). There were no significant differences of baseline age, QoL, TPV, TZI,
serum PSA levels, voided volume, or PVR between both groups (Table 1). After medical treatment for 1 month, 89/116 (76.7%) patients receiving tolterodine and 218/279 (78.1%) patients receiving
doxazosin reported an improved outcome (GRA >= 1 point).
Figure 1 showed the parameters at baseline and changes of parameters after treatment for 1month (visit 1) and 3 months (visit 2) in both groups. The mean IPSS-T, IPSS-S decreased, and QoL
improved significantly in both groups. Significant increased Qmax, voided volume, decreased IPSS-V and PVR were noted only in patients receiving doxazosin. There was no significant increase of
PVR (from 50.1 to 60.4 ml, p=0.106), and no patient developed urinary retention after tolterodinie monotherapy for 1 month (Table 2). The reported adverse effects (AE) including 13 dry mouth
(9.8%), 10 blurred vision (7.6%), 7 dry eye (5.3%), 6 dysuria (4.5%), 3 constipation (2.3%) in patients received tolterodine; and 2 dizziness (1.5%), 1 general weakness (0.8%), and 1 palpitation
(0.8%) in patients received doxazosin. No significant differences of reported AE between both groups.
When comparing baseline parameters between those with GRA>=1 and GRA<1 after treatment, patients with higher baseline Qmax receiving tolterodine (p=0.046) and those with higher TZI
receiving doxazosin (p=0.037) more likely to have GRA>=1 after treatment (Table 3). For those with GRA<1 after first-line doxazosin, 89% of patients continuing doxazosin monotherapy reported
GRA>=1 and 70% of patients received additional antimuscarinic therapy had GRA>=1 at 3 months. For those with GRA<1 after first-line tolterodine monotherapy, 78% of patients continuing
tolterodine monotherapy reported GRA>=1 at 3 months and 73% of patients received additional doxazosin therapy had GRA>=1 at 3 months.
Table 1. Baseline parameters between IPSS-V/S>1 and IPSS-V/S<=1
Table 2. Parameters changes after medical treatment for 1 month
Initial treatment with doxazosin for patients with IPSS-V/S>1 and tolterodine for patients with
IPSS-V/S<=1 and is safe and feasible. Using IPSS-V/S ratio can help to guide the initial medical
treatment of male LUTS, especially for the PCPs.
1.McVary KT et al, Update on AUA Guideline on the Management of Benign Prostatic Hyperplasia. J Urol. 2011;185:1793-803.
2.Djavan B et al, An algorithm for medical management in male lower urinary tract symptoms. Curr Opin Urol. 2011;21:5-12.
3.Kaplan SA et al, Antimuscarinics for treatment of storage lower urinary tract symptoms in men: a systematic review. Int J Clin Pract.
4.Liao CH, Chung SD, Kuo HC. Diagnostic value of International Prostate Symptom Score voiding-to-storage subscore ratio in male lower urinary
tract symptoms. Int J Clin Pract. 2011;65:552-8.
Figure 1. Parameters changed after treatment, and the comparison between two
groups by multiple measurement test.