Silodosin is a new selective therapy with a high pharmacologic selectivity for the α1A-adrenoreceptor.
Our aim was to test silodosin's superiority to placebo and noninferiority to tamsulosin and discuss the findings in the context of a comprehensive literature review of the new compound silodosin.
Design, setting, and participants
We conducted a multicenter double-blind, placebo- and active-controlled parallel group study. A total of 1228 men ≥50 yr of age with an International Prostate Symptom Score (IPSS) ≥13 and a urine maximum flow rate (Qmax) >4 and ≤15
We calculated the change from baseline in IPSS total score (primary), storage and voiding subscores, quality of life (QoL) due to urinary symptoms, and Qmax. Responders were defined on the basis of IPSS and Qmax by a decrease of ≥25% and an increase of ≥30% from baseline, respectively.
Results and limitations
The change from baseline in the IPSS total score with silodosin and tamsulosin was significantly superior to that with placebo (p
Active treatments were well tolerated, and discontinuation rates due to adverse events were low in all groups (2.1%, 1.0%, and 1.6% with silodosin, tamsulosin, and placebo, respectively). The most frequent adverse event with silodosin was a reduced or absent ejaculation during orgasm (14%), a reversible effect as a consequence of the potent and selective α1A-adrenoreceptor antagonism of the drug. The incidence was higher than that observed with tamsulosin (2%); however, only 1.3% of silodosin-treated patients discontinued treatment due to this adverse event.
Silodosin is an effective and well-tolerated treatment for the relief of both voiding and storage symptoms in patients with lower urinary tract symptoms suggestive of bladder outlet obstruction thought to be associated with benign prostatic hyperplasia. Its overall efficacy is not inferior to tamsulosin. Only silodosin showed a significant effect on nocturia over placebo.
ClinicalTrials.gov Identifier NCT00359905.
Keywords: Silodosin, Tamsulosin, BPH, LUTS.
Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate caused by cellular hyperplasia of both glandular and stromal elements . As the prostate increases in size, it may occlude the lumen of the prostatic urethra, obstructing urine flow . However, studies have shown that prostate size and urinary flow rate usually do not correlate with the severity of lower urinary tract symptoms (LUTS), which may vary from subject to subject . In clinical practice, patients are treated for LUTS suggestive of bladder outlet obstruction (BOO) due to BPH, often called “LUTS/BPH.”
Even if voiding symptoms are the most prevalent in cases of LUTS/BPH, patients usually perceive the storage symptoms as the most bothersome group of symptoms . The objective of therapy for such patients is to improve LUTS/BPH and hence quality of life (QoL). In addition, treatment is aimed at preventing complications such as acute urinary retention or upper urinary tract dilation consequent to BOO. Existing medical therapy includes α-blockers, which are currently the preferred first-line therapy for all men with moderate or severe LUTS/BPH , and 5α-reductase inhibitors (5-ARIs), which are a recommended treatment option for men with moderate or severe LUTS/BPH and an enlarged prostate. α-Blockers can be used regardless of prostate size because they act on the dynamic/neurally mediated contraction of the muscular stroma that is increased in BPH; 5-ARIs act by shrinking the stromal component of the gland. Both components are thought to contribute to the symptoms and impairment of outflow in patients with LUTS/BPH .
Nonselective α1-adrenoceptor blockers increase urinary flow rate and improve symptoms in men with symptomatic BPH; however, they may be associated with side effects related to peripheral vasodilation, such as postural hypotension, dizziness, and headache , , and . Conversely, drugs with a high affinity for α1A-adrenoceptors may be more prostate specific and may maintain the therapeutic response in the treatment of symptomatic BPH with less effect on blood pressure and fewer cardiovascular side effects  and .
Silodosin is a new agent with high selectivity for α1A-receptors, which predominate in the male bladder outflow tract relative to α1B-receptors. It has been demonstrated in vitro that silodosin's α1A-to-α1B binding ratio is extremely high (162:1), suggesting the potential to markedly reduce dynamic neurally mediated smooth muscle relaxation in the lower urinary tract while minimizing undesirable effects on blood pressure regulation . In this context, the evaluation of the uroselectivity of silodosin versus that of tamsulosin and prazosin in vivo has shown good uroselectivity (determined from the ratio of the dose-reducing intraurethral pressure as contrasted to blood pressure) in rats and dogs  and .
This paper reports the results of the first randomized placebo-controlled European study with silodosin in the treatment of patients with LUTS/BPH. The study compared silodosin with the effective and widely used drug tamsulosin .
2. Patients and methods
2.1. Study design
A multicenter double-blind, placebo- and active-controlled parallel group clinical study was conducted in 72 hospital clinics and inpatient units in 11 countries in Europe. After a wash-out phase of 14 d and a 4-wk single-blind placebo run-in period, subjects who met the selection criteria were randomly assigned (in a ratio of 2:2:1, with stratification by center, with blocks of five assigned to each center, produced and managed centrally by an international contract research organization) to a 12-wk treatment with silodosin 8
Eight visits were foreseen: at day −42 (start of the wash-out period) and day −28 (start of the placebo run-in period); at baseline (pre- and postrandomization); and after 7, 14, 28, 56, and 84 d of treatment (or in the case of premature study termination).
Prerandomization procedures consisted of the collection of a medical history (including a urologic history), a check of concomitant medications, a physical examination (including a digital rectal examination), and a postvoid residual volume determination by ultrasound.
The International Prostate Symptom Score (IPSS) questionnaire (including question 8, BPH-related health status), a validated instrument widely used for the assessment of symptom severity in patients with BPH , was administered to the patients at screening, at baseline, and after 7, 14, 28, 56, and 84 d of treatment (or in the case of premature study termination). Because the study was performed in several European countries and involved patients speaking different languages, the questionnaire was linguistically validated by the MAPI Institute (an international company that specialized in linguistic validation for appropriate cross-cultural use and interpretation of patient-reported assessments) in the relevant languages.
Peak urine maximum flow rate (Qmax) was also measured once 2–6
Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured at each visit, with the subject supine at rest for at least 5
2.2. Study population
Men ≥50 yr of age with LUTS (defined by a stable IPSS total score ≥13 points), BOO (defined by a Qmax between 4 and 15
2.3. Study end points and statistical analyses
The primary end point of the study was to demonstrate the superiority of silodosin to placebo and its noninferiority to tamsulosin for the relief of LUTS associated with BPH and suggestive of BOO. This was measured by a change from baseline in the total score (questions 1–7) of the IPSS questionnaire (primary efficacy parameter).
The total number of subjects to be randomized was set at 820 (328 for silodosin 8
Secondary efficacy parameters were as follows: improvement in storage and voiding symptoms subscores, QoL due to urinary symptoms (question 8 of the IPSS), Qmax, and percentage of treatment responders by IPSS (decrease from baseline ≥25%) and by Qmax (increase from baseline ≥30%).
Statistical analyses were performed using the following procedures. For the analysis of the primary efficacy variable, the superiority of the active treatments (silodosin and tamsulosin) versus placebo was tested first in the intent-to-treat (ITT) population (all subjects who had a baseline IPSS assessment and at least one valid postbaseline IPSS assessment). Next, the noninferiority of silodosin versus tamsulosin was tested in the PP population (all subjects who completed the study without any major protocol violation). Last, because all the planned tests were satisfied, the superiority of silodosin versus tamsulosin was tested (ITT population). For the secondary efficacy variables, the superiority of the active treatments (silodosin and tamsulosin) versus placebo was tested first, followed by the comparison between silodosin and tamsulosin.
The overall treatment group comparisons of the change from baseline in the IPSS total score, by visit and at end point (in both ITT and PP populations), were estimated based on adjusted means obtained from the main analysis of the covariance model, which included terms for treatment, pooled center, and baseline value.
The percentage of responders to IPSS and the percentage of responders to Qmax were summarized at each visit and at end point by treatment group; comparisons between each of the active treatment groups and placebo and between silodosin and tamsulosin were made using the Cochran Mantel Haenszel test, stratified by pooled center, for both populations.
A post hoc analysis was conducted in the subgroup of patients with nocturia at baseline (defined as at least two voids per night), as assessed by question 7 of the IPSS.
In terms of safety, the safety population was defined as all subjects who were randomized and who received at least one dose of double-blind study medication. Safety was assessed primarily on the basis of TEAEs occurring in the different groups postrandomization. In addition, the change from baseline was evaluated for the following safety parameters: DBP, SBP, and HR in a supine position and after standing (orthostatic test), laboratory determinations, ECG findings, and physical examination.
3.1. Disposition of patients
A total of 1228 patients were screened, 955 of whom were randomized to receive silodosin 8
3.2. Demographics and other baseline characteristics
Table 1 summarizes the demographic and baseline characteristics of the safety population. No statistically significant differences were seen between the three treatment groups with respect to age, body mass index, IPSS total score, storage and voiding subscores, and QoL due to urinary symptoms. Of note, 424 patients (44.4%) were hypertensive, and many subjects were on concomitant antihypertensive medications. At baseline, many patients had a past or current history of erectile dysfunction (24.0%) or complained of ejaculation disorders. These included orgasm semen quantity reduced (8.3%), orgasm semen force reduced (6.9%), and orgasm with no semen (0.8%), with an overall 24.0% rate of pretreatment ejaculatory disorders.
|Silodosin 8 mg||Tamsulosin 0.4 mg||Placebo||Total||p value|
|Age, yr, n (%)|
|158 (41.5)||157 (40.9)||75 (39.5)||390 (40.8)|
|168 (44.1)||183 (47.7)||93 (48.9)||444 (46.5)|
|55 (14.4)||44 (11.5)||22 (11.6)||121 (12.7)|
|Race, n (%)|
|381 (100.0)||384 (100.0)||190 (100.0)||955 (100.0)||Not estimable|
|BMI, kg/m2, n (%)|
|84 (22.0)||109 (28.4)||46 (24.2)||239 (25.0)|
|238 (62.5)||214 (55.7)||118 (62.1)||570 (59.7)|
|59 (15.5)||61 (15.9)||25 (13.2)||145 (15.2)||0.624|
|IPSS total score|
|IPSS storage subscore|
|IPSS voiding subscore|
|QoL due to urinary symptoms, n (%)|
|0 (0.0)||3 (0.8)||0 (0.0)||3 (0.3)|
|2 (0.5)||6 (1.6)||0 (0.0)||8 (0.8)|
|27 (7.1)||23 (6.0)||12 (6.3)||62 (6.5)|
|98 (25.7)||105 (27.3)||44 (23.2)||247 (25.9)|
|140 (36.7)||135 (35.2)||65 (34.2)||340 (35.6)|
|98 (25.7)||95 (24.7)||57 (30.0)||250 (26.2)|
|16 (4.2)||17 (4.4)||10 (5.3)||43 (4.5)|
|0 (0.0)||0 (0.0)||2 (1.1)||2 (0.2)|
|Urine Qmax, ml/s|
3.3. Efficacy results
3.3.1. Change from baseline in International Prostate Symptom Score total score (primary efficacy parameter)
|Silodosin 8 mg||Tamsulosin 0.4 mg||Placebo|
|Change from baseline to end point, adjusted means||−7.0||−6.7||−4.7|
|Difference active vs placebo (95% CI)||−2.3 (−3.2, −1.4)*||−2.0 (−2.9, −1.1)*||–|
|Difference tamsulosin vs silodosin (95% CI)||0.3 (−0.4, 1.0)†||–||–|
|Change from baseline to week 12, adjusted means||−7.0||−6.7||−4.8|
|Difference active vs placebo (95% CI)||−2.2 (−3.2. −1.3)*||−1.9 (−2.8, −0.9)*||–|
|Difference tamsulosin vs silodosin (95% CI)||0.4 (−0.4, 1.1)†||–||–|
For all treatment groups, there was no plateau in response; however, the largest decreases in the total IPSS score occurred rapidly, within the first 2 wk of treatment. Superiority of active treatments versus placebo was observed with highly statistically significant differences at all weeks (p
3.3.2. Responder rates according to International Prostate Symptom Score total score
In all three treatment groups, the percentage of IPSS responders progressively increased from baseline to week 12. At study end, 66.8% and 65.4% of the patients receiving silodosin or tamsulosin were responders (respectively), compared with 50.8% in the placebo group.
The differences versus placebo were highly significant (p
3.3.3. Voiding and storage subscores
Table 3 shows the mean change from baseline to end point in the IPSS subscore of voiding symptoms (questions 1, 3, 5, and 6) and of storage symptoms (questions 2, 4, and 7). The statistically significant superiority of both active treatments versus placebo on voiding and storage subscores was observed at all weeks of treatment. The comparison between silodosin and tamsulosin did not show a statistically significant difference, even if a numerical difference in favor of silodosin was observed in the voiding subscore. Of note, in the subgroup of patients with nocturia at baseline (n
|Treatment arm||IPSS storage symptoms||IPSS voiding symptoms|
|Difference (95% CI) vs placebo||Change
|Difference (95% CI) vs placebo|
|Silodosin||−2.5||−0.7† (−1.1, −0.2)||−4.5||−1.7* (−2.2, −1.1)|
|Tamsulosin||−2.4||−0.6† (−1.1, −0.2)||−4.2||−1.4* (−2.0, −0.8)|
3.3.4. Quality of life
An improvement in the change from baseline in QoL due to urinary symptoms (question 8 of the IPSS) was reported for all treatment groups (−1.1 for silodosin, −1.1 for tamsulosin, and −0.8 for placebo). Once again, highly statistically significant differences were observed between active treatments and placebo at all weeks (at end point p
|No. (%)||No. (%)||No. (%)|
|29 (7.8)||32 (8.5)||12 (6.5)|
|94 (25.3)||103 (27.4)||43 (23.2)|
|248 (66.9)||241 (64.1)||129 (69.7)|
|163 (44.0)||168 (44.7)||63 (34.0)|
|82 (22.1)||99 (26.3)||38 (20.5)|
|126 (34.0)||109 (29.0)||84 (45.4)|
* Data analysis for week 12 was based on last observation carried forward.
3.3.5. Maximum flow rate
A larger increase from baseline in Qmax (milliliters per second) was observed for both active treatment groups compared with placebo but was not statistically significant. The adjusted mean change from baseline to end point was 3.77
3.4. Safety results
3.4.1. Treatment-emergent adverse events
Overall, the percentage of subjects who reported at least one TEAE was 34.9% (133 of 381) for subjects in the silodosin group, 28.9% (111 of 384) in the tamsulosin group, and 24.2% (46 of 190) in the placebo group (silodosin vs placebo: p
The percentage of subjects who discontinued the study due to a TEAE was small and not statistically different in all treatment groups (silodosin 2.1%, eight subjects; tamsulosin 1.0%, four subjects; placebo 1.6%, three subjects). The most common TEAE leading to discontinuation was failure of ejaculation (five subjects in the silodosin group and one in the tamsulosin group). This TEAE was reversible after study discontinuation.
Nine subjects of 955 (0.9%) experienced a serious TEAE; of these, three were considered possibly related to the study drug by the treating investigator: prostate cancer and supraventricular arrhythmia (silodosin) and anxiety (tamsulosin). Two subjects died during the study; both deaths were unrelated to the drugs used in the study.
3.4.2. Other safety parameters
No clinically meaningful changes were recorded for any of the laboratory parameters, vital signs, or ECGs observed during the study in any of the treatment groups. Table 5 presents the supine DBP, SBP, and HR and the change from baseline in DBP, SBP, and HR observed with the silodosin, tamsulosin, and placebo groups. No clinically relevant or statistically significant differences versus placebo were observed with silodosin. An important characteristic of silodosin is the lack of clinically relevant or statistically significant changes in blood pressure or heart rate versus placebo. However, a minor but statistically significant difference versus placebo was observed with tamsulosin.
|Supine systolic BP|
|133.8 (12.61)||133.0 (13.29)||132.8 (13.57)|
|−1.4 (−3.0, 0.1)||−1.8 (−3.4, −0.3)||–|
|−0.4 (−1.7, 0.9)||–||–|
|Supine diastolic BP|
|80.6 (7.47)||80.5 (7.99)||80.6 (7.70)|
|−0.3 (−1.4, 0.7)||−1.0 (−2.1, 0.0)||–|
|−0.7 (−1.5, 0.2)||–||–|
|Supine heart rate|
|67.4 (8.83)||67.8 (9.10)||67.3 (8.43)|
|−0.3 (−1.6, 1.0)||0.2 (−1.1, 1.5)||–|
|0.5 (−0.5, 1.5)||–||–|
No subject experienced a marked decrease in blood pressure when performing the postrandomization orthostatic test after the first dosing of the drug. Only a few subjects in both active treatment groups reported an increase in HR >20 beats per minute without any clinically important change in SBP or DBP.
This prospective statistically well-powered study evaluated the efficacy and safety of the new highly selective agent silodosin, an α1A-receptor, for the treatment of moderate to severe LUTS due to BPH. A population of patients with LUTS/BPH who were representative of those seen in clinical practice in terms of age, concomitant diseases, and medication was selected. In the patient group, approximately 60% were elderly, and about 57% were on concomitant antihypertensive medication.
In this study, silodosin proved to be an effective drug for the treatment of both storage and voiding LUTS associated with BPH because a statistically significant and potentially clinically relevant difference versus placebo was observed in the IPSS total score, in the storage and voiding subscores, and in QoL due to urinary symptoms. The improvement became evident soon after the initiation of therapy. The treatment effect with silodosin appeared to be at least equivalent to and numerically consistently greater than that seen with tamsulosin when considering the change from baseline in the IPSS total score, in the voiding subscore, and in the responder rates, even if the differences were not statistically significant. There was also a greater benefit seen when considering the QoL on active therapy with either silodosin or tamsulosin as compared with placebo.
It is noteworthy that the selective effect of α1A-receptor antagonism seemed to offer a clinically relevant benefit not only on voiding but also on storage symptoms. Of note, only the effect of silodosin (and not of tamsulosin) on nocturia was significantly better than that of placebo. The mechanism of this action remains to be clarified.
In this study, treatment with silodosin also showed an early and sustained increase in Qmax; however, the difference versus placebo was not statistically significant. A similar order of magnitude for the flow rate was seen with the active comparator tamsulosin, which has been clearly documented in the past to produce significant changes when compared with placebo.
The first randomized double-blind, placebo-controlled study that was conducted with silodosin in Japan recruited men ≥50 yr of age with an IPSS of ≥8 and a QoL score of ≥3. Patients were randomized to receive silodosin 4
Marks and colleagues assessed the efficacy and safety of silodosin 8
A long-term open-label extension study of patients from these two studies was conducted over 40 wk, with all patients receiving silodosin 8
Because the efficacy of both tamsulosin and silodosin appear to be very similar, the question has to be posed regarding the potential additional advantage of silodosin. Studies conducted recently have suggested that silodosin as a consequence of its high subtype selectivity is less likely than tamsulosin to have significant cardiovascular side effects either when used alone or in combination with other agents, which may affect blood pressure. This is particularly important and relevant in more elderly patients.
Kobayashi et al.  provided evidence for this suggestion. They evaluated the efficacy on the urethra (intraurethral pressure) and cardiovascular system (hypotension) of silodosin (α1A-adrenoceptor antagonist) and tamsulosin (α1A+1D-adrenoceptor antagonist) in dogs with BPH altered with age. Under anesthesia, the increase in intraurethral pressure evoked by hypogastric nerve stimulation was measured, together with the level of systemic mean blood pressure. Each drug was administered intravenously in progressively increasing doses. Silodosin (0.3–300
In a placebo-controlled open-label clinical crossover study evaluating potential interaction with a phosphodiesterase inhibitor , 22 healthy men 45–78 yr of age received 8
Although it is a widely held view among clinicians that EjD is a consequence of an effect on the bladder neck, it is in fact not true retrograde ejaculation but rather “anejaculation” caused by an effect on the ejaculatory apparatus (prostate, seminal vesicles, and vasa) and indeed has been coded incorrectly as retrograde ejaculation in several clinical studies . It has been recognized for many years that the vas is an excellent pharmacologic model for the α1A-receptor . Although it is possible that the clinical differences between silodosin and tamsulosin as compared with other α1-adrenoceptor antagonists do not exclusively relate to their subtype selectivity , additional properties of these drugs such as a proposed insurmountable antagonism in the vas deferens  or additional effects on other receptor systems (eg, dopamine and/or serotonin ) should be considered. Finally, it has been proposed that abnormal ejaculation is not primarily regulated at the level of the vas deferens but rather at central nervous sites that control its function .
This is clearly a typical side effect of α1-adrenoreceptor antagonists, particularly those with selectivity for α1A-adrenoreceptors, because this subtype is distributed throughout the organs participating in the emission phase of ejaculation . Nonclinical studies have shown that α-adrenoreceptors, particularly α1A-adrenoreceptors, are essential for the physiologic contraction of the vas deferens and hence for sperm delivery from the testes to the urethra . Reduced ejaculation is caused by an impaired function of the vas deferens rather than by alterations in sperm formation, number, or function . This effect does not represent a safety concern because it indicates only a reduction in semen volume that is reversible (within a few days) upon discontinuation of treatment  and , and it is not perceived as particularly bothersome (in this study, the discontinuation rates were very low in all groups and were comparable with placebo).
It is now well established that EjD is commonly associated with both increasing age and the presence of LUTS , , , and . The Multinational Survey of the Aging Male-7 results confirmed the significant relationship between LUTS and EjD in aging men.
A post hoc analysis of the North American studies on silodosin  suggested that EjD may be a predictor of the efficacy of the α1-adrenoreceptor blockade. Roehrborn and colleagues found that 28.1% of patients in these studies experienced EjD and reported that these patients experienced a greater improvement in symptoms and a clinically meaningful greater improvement in flow rate than those who did not experience EjD . Homma et al.  carried out a similar analysis evaluating improvements in symptoms in the Japanese study . The silodosin subgroup with failure of ejaculation experienced a greater reduction in total IPSS than the silodosin subgroup without impairment of ejaculation and the placebo subgroup (−11.8 vs −7.2 vs −5.3, respectively). Interestingly, the dropout rates in both of the silodosin groups were very similar.
As expected for a highly uroselective drug, silodosin appears to be a safe drug that is at least equivalent to tamsulosin in efficacy. A major advantage of this drug is its lack of cardiovascular side effects. It has no clinically relevant effect on blood pressure when measured either in the supine position or during orthostatic testing. This is important because most patients treated for LUTS associated with BPH are elderly and often on concomitant antihypertensive therapy or taking agents such as phosphodiesterase inhibitors. No unfavorable effect has been observed on ECG or laboratory tests, including liver function tests and tests of creatinine and glucose levels.
This large multinational study has confirmed the results of previous studies, demonstrating silodosin to be an effective and safe treatment for the relief of both voiding and storage symptoms in patients with benign prostatic enlargement consequent upon BOO due to BPH. It may be particularly useful in more elderly patients where there is the potential for drug–drug interactions and where potential cardiovascular side effects need to be minimized.
Study concept and design: Chapple, Montorsi.
Acquisition of data: Chapple, Montorsi, Tammela, Wirth, Koldewijn, Fernández Fernández.
Analysis and interpretation of data: Chapple, Montorsi, Tammela, Wirth, Koldewijn, Fernández Fernández.
Drafting of the manuscript: Chapple, Montorsi, Tammela, Wirth, Koldewijn, Fernández Fernández.
Critical revision of the manuscript for important intellectual content: Chapple, Montorsi, Wirth, Koldewijn, Fernández Fernández.
Statistical analysis: None.
Obtaining funding: None.
Administrative, technical, or material support: None.
Other (specify): None.
Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Christopher R. Chapple and Francesco Montorsi are consultants and researchers for Recordati. Teuvo L.J. Tammela, Manfred Wirth, Evert Koldewijn, and Eldiberto Fernández Fernández are researchers for Recordati.
Funding/Support and role of the sponsor: Recordati Ireland Ltd, Ringaskiddy, County Cork, Ireland, was involved in the design and conduct of the study, collection of the data, management of the data, analysis, interpretation of the data, preparation, review, and approval of the manuscript.
Acknowledgement statement: The authors wish to thank Dr. Massimo Casi, senior clinical project leader, for his dedicated help and support in finalizing the manuscript.
Appendix A. Complete List of Study Participants
Finland: T. Forsell (Kotka); P. Hellström (Oys); M. Multanen (Kouvola); T.L.J. Tammela (Tampere)
France: H. Botto (Suresnes); D. Chevallier (Nice)
Germany: F. König (Berlin); M. Schulze (Markkleeberg); J. Willgerodt (Leipzig); M. Wirth (Dresden); A. Von Keitz (Marburg)
Italy: F. Gaboardi (Milan); V. Gentile (Rome); M. Motta (Catania); P. Rigatti (Milano); R.M. Scarpa (Orbassano); O. Risi (Treviglio)
The Netherlands: E. Koldewijn (Eindhoven); E. Meuleman (Amsterdam); V. Van de Walle (Geleen)
Poland: P. Chlosta (Kielce); B. Darewicz (Bialystok); A. Dobrowolski (Myslowice); W. Dudziak (Srem); A. Gajda (Warszawa); P. Wedzikowski (Lodz); R. Jarema (Warszawa); R. Szwedowski (Opole); J. Szyperski (Bydgoszcz); P. Trypens (Warszawa); M. Wyczółkowski (Krakow)
Romania: F. Bajan (Pitesti); N. Calomfirescu (Bucharest); M. Dinu (Bucharest); C. Gingu (Bucharest); V. Jinga (Bucharest); C. Nitoiu (Bucharest)
Russia: S. Al-Shukri (St. Petersburg); V.P. Avdoshin (Moscow); I.A. Gorelov (St. Petersburg); I.S. Gorelov (St. Petersburg); V.K. Kheifets (St. Petersburg); B.V. Kunin (St. Petersburg); V.I. Kuzmin (St. Petersburg); O.B. Loran (Moscow); E.B. Mazo (Moscow); L.S. Mikhailov (St. Petersburg); I. Sedavnykh (St. Petersburg); A.V. Shanava (St. Petersburg); V.N. Shirshov (Moscow); V.N. Surikov (Moscow); A. Zhivov (St. Petersburg); M. Forkampf-Laue (St. Petersburg)
Spain: J. Caballero Alcántara (Marbella); E. Leon Dueñas (Sevilla); E. Fernández Fernández (Madrid); J.M. Fernández Gómez (Oviedo); F. Jiménez Cruz (Valencia); J.A. Portillo Martín (Santander)
Ukraine: A.A. Lyulko (Zaporizhzhya); A.V. Lyulko (Dnipropetrovsk); I. Gorpynchenko (Kyiv); F. Kostyev (Odesa); V. Lesovoy (Kharkiv); S. Pasiechnikov (Kyiv); V. Pirogov (Kyiv); V. Zaytsev (Chernivtsi)
United Kingdom: C.R. Chapple (Sheffield); S. Natale (Plymouth); R. Persad (Bristol); M. Speakman (Taunton, Somerset); A. Thorpe (Newcastle upon Tyne)
-  C. Chapple. Medical treatment for benign prostatic hyperplasia. BMJ. 1992;304:1198-1199 Crossref.
-  G.M. Clifford, R.D.T. Farmer. Medical therapy for benign prostatic hyperplasia: a review of the literature. Eur Urol. 2000;38:2-19 Crossref.
-  M.J. Barry, A.T. Cockett, H.L. Holtgrewe, et al. Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol. 1993;150:351-358
-  T.J. Peters, J.L. Donovan, H.E. Kay, et al. The International Continence Society “Benign Prostatic Hyperplasia” Study: the botherosomeness of urinary symptoms. J Urol. 1997;157:885-889
-  S. Madersbacher, G. Alivizatos, J. Nordling, C. Rioja Sans, M. Emberton, JJMC.H. de la Rosette. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol. 2004;46:547-554 Crossref.
-  H. Lepor. Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007;9:181-190
-  C.R. Chapple. Pharmacological therapy of benign prostatic hyperplasia/lower urinary tract symptoms: an overview for the practicing clinician. BJU Int. 2004;94:738-744 Crossref.
-  H. Lepor, S. Auerbach, A. Puras-Baez, et al. A randomised, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. J Urol. 1992;148:1467-1474
-  C.R. Chapple, P. Carter, T.J. Christmas, et al. A three-month double-blind study of doxazosin as treatment for benign prostatic bladder outlet obstruction. J Urol. 1994;74:50-56 Crossref.
-  Michel MC, Grübbel B, Möllhoff S, et al. 1-Adrenoceptor affinities of drugs for the treatment of benign prostatic hyperplasia in human prostate, rat tissues and at cloned subtypes. Abstract presented at: 23rd Congress of the Société Internationale d’Urologie; September 18–24, 1994; Sydney, Australia. Abstract 649.
-  A. Hatano, H. Takahashi, M. Tamaki, T. Komeyama, T. Koizumi, M. Takeda. Pharmacological evidence of district α1-adrenoceptors subtypes mediating the contraction of human urethra and peripheral artery. Br J Pharmacol. 1994;113:723-728 Crossref.
-  S. Tatemichi, K. Kobayashi, A. Maezawa, et al. α1-Adenoceptor subtype selectivity and organ specificity of silodosin (KMD-3213). Yakugaku Zasshi. 2006;126:209-216 Crossref.
-  K. Akiyama, M. Hora, S. Tatemichi, et al. KMD-3213, a uroselective and long-acting alpha(1a)-adrenoceptor antagonist, tested in a novel rat model. J Pharmacol Exp Ther. 1999;291:81-91
-  K. Akiyama, H. Noto, O. Nishizawa, et al. Effect of KMD-3213, an alpha1A-adrenoceptor antagonist, on the prostatic urethral pressure and blood pressure in male decerebrate dogs. Int J Urol. 2001;8:177-183 Crossref.
-  K. Kawabe, M. Yoshida, Y. Homma, Silodosin Clinical Study Group. Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int. 2006;98:1019-1024 Crossref.
-  L.S. Marks, M.C. Gittelman, L.A. Hill, W. Volinn, G. Hoel. Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol. 2009;181:2634-2640 Crossref.
-  C. Chapple. Andersson KE Tamsulosin: an overview. World J Urol. 2002;19:397-404
-  L.S. Marks, M.C. Gittelman, L.A. Hill, W. Volinn, G. Hoel. Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month, open-label extension study. Urology. 2009;74:1318-1322 Crossref.
-  S. Kobayashi, Y. Tomiyama, S. Tatemichi, Y. Hoyano, M. Kobayashi, Y. Yamazaki. Effects of silodosin and tamsulosin on the urethra and cardiovascular system in young and old dogs with benign prostatic hyperplasia. Eur J Pharmacol. 2009;613:135-140 Crossref.
-  S.A. MacDiarmid, L.A. Hill, W. Volinn, G. Hoel. Lack of pharmacodynamic interaction of silodosin, a highly selective alpha1a-adrenoceptor antagonist, with the phosphodiesterase-5 inhibitors sildenafil and tadalafil in healthy men. Urology. 2010;75:520-525 Crossref.
-  M.M. van Dijk, de la Rosette JJMCH, M.C. Michel. Effects of alpha-1 adrenoceptor antagonists on male sexual function. Drugs. 2006;66:287-301 Crossref.
-  K. Furukawa, D.J. Rosario, D.J. Smith, C.R. Chapple, T. Uchiyama, R. Chess-Williams. Alpha 1A-adrenoceptor-mediated contractile responses of the human vas deferens. Br J Pharmacol. 1995;116:1605-1610 Crossref.
-  M.C. Michel, G. Hanft, G. Groß. Functional studies on alpha-1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle. Br J Pharmacol. 1994;111:539-546 Crossref.
-  A.J. Noble, R. Chess-Williams, C. Couldwell, et al. The effects of tamsulosin, a high affinity antagonist at functional α1A- and α1D-adrenoceptor subtypes. Br J Pharmacol. 1997;120:231-238 Crossref.
-  A. Leonardi, J.P. Hieble, L. Guarneri, et al. Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity, part I. J Pharmacol Exp Ther. 1997;281:1272-1283
-  F.A. Giuliano, P. Clement, P. Denys, L. Alexandre, J. Bernabe. Comparison between tamsulosin and alfuzosin on the expulsion phase of ejaculation in rats. BJU Int. 2006;98:876-879 Crossref.
-  J. Miller, C.C. Carson. Alpha blockers and ejaculatory function: a state of the art review. Curr Sex Health Rep. 2007;4:141-144
-  A. Sanbe, Y. Tanaka, Y. Fujiwara, et al. α1-Adrenoceptors are required for normal male sexual function. Br J Pharmacol. 2007;152:332-340
-  M.C. Michel. α1-Adrenoceptors and ejaculatory function. Br J Pharmacol. 2007;152:289-290
-  S. Hisasue, R. Furuya, N. Itoh, K. Kobayashi, S. Furuya, T. Tsukamoto. Ejaculatory disorder caused by alpha-1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission. Int J Urol. 2006;13:1311-1316 Crossref.
-  K. Kobayashi, N. Masumori, S.I. Hisasue, et al. Inhibition of seminal emission is the main cause of anejaculation induced by a new highly selective α1A-blocker in normal volunteers. J Sex Med. 2008;5:2185-2190 Crossref.
-  W.J. Hellstrom, F. Giuliano, R.C. Rosen. Ejaculatory dysfunction and its association with lower urinary tract symptoms of benign prostatic hyperplasia and BPH treatment. Urology. 2009;74:15-21 Crossref.
-  M.H. Blanker, J.L. Bosch, F.P. Groeneveld, et al. Erectile and ejaculatory dysfunction in a community-based sample of men 50-78 years old: prevalence, concern, and relation to sexual activity. Urology. 2001;57:763-768 Crossref.
-  M.H. Blanker, A.M. Bohnen, F.P. Groeneveld, et al. Correlates for erectile and ejaculatory dysfunction in older Dutch men: a community- based study. J Am Geriatr Soc. 2001;49:436-442 Crossref.
-  R. Rosen, J. Altwein, P. Boyle, et al. Lower urinary tract symptoms and male sexual dysfunction: the Multinational Survey of the Aging Male (MSAM-7). Eur Urol. 2003;44:637-649 Crossref.
-  C.G. Roehrborn, H. Lepor, S.A. Kaplan. Retrograde ejaculation induced by silodosin is the result of relaxation of smooth musculature in the male urogenital tract and is associated with greater urodynamic and symptomatic improvement in male LUTS secondary to BPH. J Urol. 2009;181 Abstract 1922
-  Y. Homma, K. Kawabe, M. Takeda, M. Yoshida. Ejaculation disorder is associated with increased efficacy of silodosin for benign prostatic hyperplasia. Urology. 2010;76:1446-1450 Crossref.
a Department of Urology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK
b Department of Urology, Università Vita Salute San Raffaele, Milan, Italy
c Department of Urology, Tampere University Hospital, Tampere, Finland
d Department of Urology, University Hospital Carl Gustav Carus, Dresden, Germany
e Department of Urology, Catharina Hospital, Eindhoven, The Netherlands
f Department of Urology, University Hospital Ramón y Cajal, Madrid, Spain
A complete list of study participants is provided in the appendix.
© 2010 European Association of Urology, Published by Elsevier B.V.