今日の臨床サポート

頻尿

著者: 高澤直子 順天堂東京江東高齢者医療センター 泌尿器科

監修: 堀江重郎 順天堂大学大学院医学研究科 泌尿器外科学

著者校正済:2021/10/27
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. 頻尿に加えてその他の下部尿路症状(排尿症状、畜尿症状、排尿後症状)がみられる場合には、男性では前立腺肥大症か過活動膀胱、女性では過活動膀胱の可能性を考える。
  1. 頻尿のみで尿意切迫感がない場合には多尿による頻尿、自覚はないが排尿障害による多量の残尿のための頻尿、心因性頻尿が考えられる。
  1. 愁訴が夜間頻尿のみでその他の下部尿路症状に乏しい場合には、夜間多尿や睡眠障害が原因の可能性がある。
  1. 排尿と生活習慣との関連については、多くの報告があり、排尿障害を有する患者に対して、日常生活における注意点について指導することは、臨床医にとって重要な要素となる[1][2](推奨度3)。過剰な水分摂取やカフェイン摂取の抑制によって改善する可能性がある。夜間眠前飲水量の減少により、夜間頻尿の回数を減らすことはそれほど難しくない。
  1. 生活指導で頻尿の改善が認められない場合には薬物療法を開始する。中高年以降の男性であれば、前立腺肥大症に伴う下部尿路症状が主な原因と考え、残尿をみながらα1遮断薬が第1選択となる。女性であれば、性器脱などの基礎疾患の有無を確認し、尿失禁や残尿を考慮しながら抗コリン薬やβ3アドレナリン受容体作動薬を初期治療として開始する。
閲覧にはご契
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
高澤直子 : 未申告[2021年]
監修:堀江重郎 : 未申告[2021年]

改訂のポイント:
  1. 過活動膀胱に対する治療方法について新たに保険適応となった治療法を追記した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 頻尿は、排尿障害の一種であり、現在では2002年に国際禁制学会(International Continence Society、ICS)がまとめた下部尿路機能に関する用語標準化報告により、過活動膀胱(overactive bladder、OAB)による症状の1つとみなされる。
  1. 頻尿は、QOLを低下させるのみならず、社会的孤独感やself-related health(自覚的健康感)の低下を来す、頻度の高い疾患である。
  1. OABは、「尿意切迫症状を主要な症状とし、通常は頻尿および夜間頻尿を伴い切迫性尿失禁を伴うこともある状態、ただし感染や明らかな他の疾患(癌、炎症など)は除外する」という自覚症状に基づく実践的な定義に、2002年のICSで変更された。
  1. わが国におけるOABの頻度は、40歳以上で男性14.3%、女性10.8%と報告されている。
  1. OABに伴う症状のうち、男性に多い症状は夜間頻尿(38.1%)、昼間頻尿(24.6%)、尿意切迫感(20.6%)であったのに対し、女性では、腹圧性尿失禁(21.6%)、夜間頻尿(20.7%)、切迫性尿失禁(19.0%)と性差が認められた。
  1. 前立腺肥大症では、下部尿路閉塞により二次的に膀胱機能の変化が誘発され、それに伴い畜尿症状が生じると想定されている。
  1. 骨盤臓器脱では下部尿路閉塞や膀胱壁の伸展が過活動膀胱の一因と考えられている。骨盤臓器脱の修復後に過活動膀胱が改善する事がある。
  1. 夜間頻尿の原因は複雑であり、多尿、夜間多尿、膀胱畜尿障害、睡眠障害が主な原因である。
 
病歴・診察のポイント  
診断:
  1. 一般診療における診断では、症状の評価および身体的検査が重要であるが、必ずしも自覚症状と病態が一致しないこともあり、専門診療においては種々の他覚的検査が必要となる。

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文献 

著者: T T Dowd, J M Campbell, J A Jones
雑誌名: J Community Health Nurs. 1996;13(3):179-86. doi: 10.1207/s15327655jchn1303_5.
Abstract/Text Urinary incontinence (UI) is a common problem and requires adjustment to self-care. Noninvasive methods to manage UI should be tried first. Although many individuals restrict fluid intake to reduce incontinent episodes, clinical hunches suggest that adequate hydration is more useful in the management of UI. This study was conducted to determine the effects of hydration on the number of UI episodes. Women were randomly assigned to 1 of 3 groups: increase fluid intake by 500 cc, maintain fluid intake at baseline level, or decrease by 300 cc. Thirty-two women kept fluid intake and output diaries for 5 weeks. Adherence to fluid intake protocols was poor, and consequently, quantitative results were nonsignificant. However, follow-up interviews revealed that 20 women reported decreased UI episodes since participating in the study and felt that the most significant learning was their recognition of the need to increase fluid intake. Community health nurses can provide guidance in self-assessment of fluid intake patterns to help manage UI.

PMID 8916607  J Community Health Nurs. 1996;13(3):179-86. doi: 10.120・・・
著者: Charmaine M Bryant, Caroline J Dowell, Greg Fairbrother
雑誌名: Br J Nurs. 2002 Apr 25-May 8;11(8):560-5.
Abstract/Text Caffeine reduction is an internationally accepted treatment strategy for patients with urinary symptoms. However, there is little trial evidence in support of a caffeine/urinary symptom effect. A prospective randomized trial was conducted among 95 consecutive adult patients with urinary symptoms presenting to two nurse continence advisers. Frequency, urgency and leakage outcomes were tested 1 month postenrolment. Trial findings indicate that caffeine intake was reduced (P<0.0001) in the experimental group and that urgency (P=0.002) and frequency (P=0.037) outcomes were significantly improved. Caffeine practices and habits were surveyed and self-reports of caffeine effects indicate that urinary symptoms figured prominently as a reported effects but less so as a driver of caffeine reduction.

PMID 11979209  Br J Nurs. 2002 Apr 25-May 8;11(8):560-5.
著者: P Abrams, C Chapple, S Khoury, C Roehrborn, J de la Rosette, International Scientific Committee
雑誌名: J Urol. 2009 Apr;181(4):1779-87. doi: 10.1016/j.juro.2008.11.127. Epub 2009 Feb 23.
Abstract/Text PURPOSE: The 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases met from June 24-28, 2005 in Paris, France to review new developments in benign prostatic disease.
MATERIALS AND METHODS: A series of committees were asked to produce recommendations on the evaluation and treatment of lower urinary tract symptoms in older men. Each committee was asked to base recommendations on a thorough assessment of the available literature according to the International Consultation on Incontinence level of evidence and grading system adapted from the Oxford system.
RESULTS: The Consultation endorsed the appropriate use of the current terminology lower urinary tract symptoms/benign prostatic hyperplasia/benign prostate enlargement and benign prostatic obstruction, and recommended that terms such as "clinical benign prostatic hyperplasia" or "the benign prostatic hyperplasia patient" be abandoned, and asked the authorities to endorse the new nomenclature. The diagnostic evaluation describes recommended and optional tests, and in general places the focus on the impact (bother) of lower urinary tract symptoms on the individual patient when determining investigation and treatment. The importance of symptom assessment, impact on quality of life, physical examination and urinalysis is emphasized. The frequency volume chart is recommended when nocturia is a bothersome symptom to exclude nocturnal polyuria. The recommendations are summarized in 2 algorithms, 1 for basic management and 1 for specialized management of persistent bothersome lower urinary tract symptoms.
CONCLUSIONS: The use of urodynamics and transrectal ultrasound should be limited to situations in which the results are likely to benefit the patient such as in selection for surgery. It is emphasized that imaging and endoscopy of the urinary tract have specific indications such as dipstick hematuria. Treatment should be holistic, and may include conservative measures, lifestyle interventions and behavioral modifications as well as medication and surgery. Only treatments with a strong evidence base for their clinical effectiveness should be used.

PMID 19233402  J Urol. 2009 Apr;181(4):1779-87. doi: 10.1016/j.juro.20・・・
著者: Yukio Homma, Takashi Ando, Masaki Yoshida, Shinji Kageyama, Mineo Takei, Kosuke Kimoto, Osamu Ishizuka, Momokazu Gotoh, Tatsuru Hashimoto
雑誌名: Neurourol Urodyn. 2002;21(3):204-9.
Abstract/Text Frequencies of voiding and urinary incontinence are commonly measured by a patient's recall or a diary. The recommended diary length varies from 1 to 14 days, with 7 days apparently being most common. To examine the statistical precision of these different modalities, we analyzed recall data and diary data of 74 patients with urinary frequency, incontinence, or both. Recall data on voiding and incontinence frequency were systematically higher and more variable than diary data. Longer diary length provided less variable diary data. The confidence interval of diary data was calculated by applying the normal distribution to daytime voiding frequency and the Poisson distribution to daytime incontinence frequency. For daytime voiding frequency, the 95% confidence interval was estimated to be (x - 2.65, x + 2.65) (x - 1.53, x + 1.53) (x - 1, x + 1), where x is the 1-day, 3-day, and 7-day diary mean, respectively. For daytime incontinence frequency, the confidence interval depended on both the diary length and the diary mean. It was estimated to be (0, 6.39), (1.72, 4.28), (2.36, 3.64), by using a diary mean of 3 or 1-day, 7-day, and 28-day diaries, respectively. Also, it was estimated to be (0, 1.02), (1.72, 4.28), (7.66, 12.34), when the 7-day diary mean was 0.5, 3, and 10, respectively. Studies with different samples of genuine stress incontinence (n = 37) and urge incontinence (n = 25) confirmed these results. In conclusion, we believe the 7-day diary is highly reliable for estimating voiding frequency and is a reasonable option for predicting incontinence episodes. However, the diary length should be extended in a patient with rarer events of incontinence, and it should be shortened for those who are incontinent more often or who are diagnosed with voiding frequency only.

Copyright 2002 Wiley-Liss, Inc.
PMID 11948713  Neurourol Urodyn. 2002;21(3):204-9.
著者: Erik Schick, Martine Jolivet-Tremblay, Charles Dupont, Pierre E Bertrand, Jocelyne Tessier
雑誌名: Neurourol Urodyn. 2003;22(2):92-6. doi: 10.1002/nau.10079.
Abstract/Text AIMS: There is wide variation in the number of days necessary to maintain a diary and still furnish reliable data on which to base a sound clinical assessment. Estimates range from 1 day to 2 weeks, 7 days probably being the criterion standard. The goal of this retrospective study was to evaluate how much the 7-day period could be shortened without compromising the reliability of data.
METHODS: Various lengths of frequency-volume (FV) charts (from 1 day to 6 days) were compared with the standard 7-day charts on 14 FV parameters.
RESULTS: Overall results show that a 4-day dairy is nearly identical to the 7-day chart (most r > or = 0.95). Results of the 1-, 2-, and 3-day charts were frequently different statistically from the 7-day chart, whereas comparison of the 4-day chart with the 7-day chart showed no statistically significant differences. In addition, results of 4-day FV charts from a new control cohort showed no significant differences from the 7-day charts of the main cohort.
CONCLUSIONS: In conclusion, our study indicates that the 4-day chart is as reliable as the 7-day chart. This reduction in the length of time, although easier for the patients, does not compromise the diagnostic value of the FV charts.

Copyright 2003 Wiley-Liss, Inc.
PMID 12579624  Neurourol Urodyn. 2003;22(2):92-6. doi: 10.1002/nau.100・・・
著者: Ja Hyeon Ku, In Gab Jeong, Dae Jung Lim, Seok-Soo Byun, Jae-Seung Paick, Seung-June Oh
雑誌名: Neurourol Urodyn. 2004;23(4):331-5. doi: 10.1002/nau.20027.
Abstract/Text AIMS: Voiding diary duration may be related to patient compliance and burden. To test this hypothesis, we evaluated patient compliance and burden.
METHODS: Between January and July 2002, we prospectively evaluated 162 patients (57 males and 105 females, mean age 53.0, range 20-81 years) with stress urinary incontinence or lower urinary tract symptoms. At the initial visit, all patients underwent a detailed clinical evaluation including an International Prostate Symptom Score (I-PSS) assessment and were randomly requested to complete 2-day, 3-day, or 7-day voiding diaries (the three study groups). At the second visit, a simple self-administered questionnaire was completed by all patients. The questionnaire included 11 items on subject demographics and voiding diary-keeping.
RESULTS: No significant differences were found in either the accuracy of diary-keeping or the daily average number of omissions when the three groups were compared. However, as the diary duration increased, the mean burden scores increased (P = 0.005), and the mean preferred duration of the diary in the 7-day group was significantly higher than that of the 2-day or 3-day groups (P < 0.001). After categorizing patients into two groups according to the degree of patient burden, members of the group with a greater perceived burden were found to have a significantly higher I-PSS quality of life score (P = 0.045) and to have kept a diary for a longer time (P = 0.038).
CONCLUSIONS: Our results suggest that keeping a diary for 7 days may increase patient burden and thus, we recommend that the 7-day diary should be reduced to cover fewer days.

Copyright 2004 Wiley-Liss, Inc.
PMID 15227650  Neurourol Urodyn. 2004;23(4):331-5. doi: 10.1002/nau.20・・・
著者: Timothy J Wilt, Roderick MacDonald, David Nelson
雑誌名: J Urol. 2002 Jan;167(1):177-83.
Abstract/Text PURPOSE: We systematically reviewed the effectiveness and adverse effects of tamsulosin for lower urinary tract symptoms compatible with benign prostatic obstruction.
MATERIALS AND METHODS: Studies were included in analysis when they involved a randomized trial of at least 1 month in duration, men with lower urinary tract symptoms and a comparison of tamsulosin with placebo or an active control. Study, patient and outcome data were extracted onto standard forms using a prospective protocol.
RESULTS: Of the series 13 involving 3,418 men with a mean age of 64 years met our inclusion criteria. Study duration was 4 to 26 weeks. Baseline symptom scores and flow rates showed moderate lower urinary tract symptoms. Tamsulosin improved symptoms and peak urine flow compared with placebo. The weighted mean difference in the mean change from baseline for the Boyarsky symptom score for 0.4 and 0.8 mg. tamsulosin versus placebo was -1.1 (95% confidence interval [CI] -1.49 to -0.72 or 12% improvement) and -1.6 points (95% CI -2.3 to -1.0 or 16% improvement), respectively. The weighted mean difference in the mean change from baseline in peak urine flow was 1.1 (95% CI 0.59 to 1.51) and 1.1 ml. per second (95% CI 0.65 to 1.48) for 0.4 and 0.8 mg., respectively. The 0.2 to 0.4 mg. tamsulosin dose was as effective as other alpha-antagonists for improving symptoms and the flow rate, although the doses of all alpha-antagonists evaluated may not have been optimal. Treatment withdrawals and adverse effects increased markedly as the tamsulosin dose increased.
CONCLUSIONS: Tamsulosin improves lower urinary tract symptoms and flow. Its effectiveness was similar to that of other alpha-antagonists, increasing slightly at higher doses. Adverse effects were generally mild but the incidence, including treatment withdrawals, increased substantially at higher doses.

PMID 11743300  J Urol. 2002 Jan;167(1):177-83.
著者: B Djavan, M Marberger
雑誌名: Eur Urol. 1999;36(1):1-13. doi: 19919.
Abstract/Text OBJECTIVE: To assess whether the alpha1-adrenoceptor antagonists currently available for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) (alfuzosin, terazosin, doxazosin and tamsulosin) can be distinguished with regard to clinical efficacy and/or tolerability.
METHODS: Up-to-date analysis of clinical placebo-controlled or direct comparative studies with alpha1-adrenoceptor antagonists in patients with LUTS suggestive of BPO derived from a MEDLINE search in October 1998. All retrieved studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated by the percentage improvement in total symptom score and Qmax (mean end of study value relative to mean baseline value). Tolerability was evaluated by means of study withdrawal rate because of adverse events and the incidence of vasodilatatory adverse events (e.g. dizziness and orthostatic hypotension).
RESULTS: Indirect comparison of data derived from the placebo-controlled studies involving 6,333 patients and the data derived from the direct comparative studies involving 507 patients demonstrate that all alpha1-adrenoceptor antagonists (alfuzosin, terazosin, doxazosin and tamsulosin) produce comparable improvements in LUTS and urinary flow. Total symptom score is in general improved by 30-40% and Qmax by 16-25%. The difference between currently available alpha1-adrenoceptor antagonists is related to their side effect profile. Alfuzosin (especially the sustained release formulation) and tamsulosin (modified release formulation 0.4 mg) seem to be better tolerated than terazosin and doxazosin. The percentage of patients that withdrew due to bothersome side effects with alfuzosin and tamsulosin 0.4 mg was comparable to that with placebo (about 4-10%) whereas in the terazosin and doxazosin studies an additional 4-10% of patients dropped out because they did not tolerate the therapy. Tamsulosin has less effect on blood pressure than alfuzosin (especially in elderly patients) and causes less symptomatic orthostatic hypotension during orthostatic stress testing than terazosin.
CONCLUSIONS: All alpha1-adrenoceptor antagonists seem to have similar efficacy in improving symptoms and flow. The difference between alpha1-adrenoceptor antagonists is related to their side effect profile. Alfuzosin and tamsulosin appear to be better tolerated than doxazosin, terazosin and prazosin.

PMID 10364649  Eur Urol. 1999;36(1):1-13. doi: 19919.
著者: Isao Ikemoto, Hiroshi Kiyota, Yukihiko Ohishi, Kazuhiro Abe, Hirokazu Goto, Kouichi Kishimoto, Kenta Miki
雑誌名: Int J Urol. 2003 Nov;10(11):587-94.
Abstract/Text BACKGROUND: The aim of the study presented here was to stratify drug therapy for patients with benign prostatic hyperplasia (BPH) displaying various voiding symptoms.
METHODS: Two different alpha1-adrenoceptor antagonists; tamsulosin hydrochloride (Tam) and naftopidil (Naf ), were administered to 96 patients with BPH for 8 weeks in a crossover study.
RESULTS: With the administration of both drugs, the International Prostate Symptom Score (I-PSS) significantly decreased and the maximum urinary flow significantly increased. Whereas Naf monotherapy decreased the I-PSS for storage symptoms, Tam monotherapy decreased the I-PSS for voiding symptoms. In both the Naf-to-Tam and Tam-to-Naf groups, crossover was effective when the initial drug was judged subjectively and objectively to have been ineffective. Compliance was acceptable with both drugs.
CONCLUSION: Our results show that either Naf or Tam can be used to treat patients on the basis of objective and subjective assessment of voiding symptoms. Our findings should be helpful for patient guidance and treatment of BPH.

PMID 14633083  Int J Urol. 2003 Nov;10(11):587-94.
著者: Momokazu Gotoh, Osamu Kamihira, Tsuneo Kinukawa, Yoshinari Ono, Shinichi Ohshima, Hideki Origasa, Tokai Urological Clinical Trial Group
雑誌名: BJU Int. 2005 Sep;96(4):581-6. doi: 10.1111/j.1464-410X.2005.05688.x.
Abstract/Text OBJECTIVES: To compare the efficacy and safety of two alpha1a/alpha1d adrenoceptor (AR) antagonists with different affinity for the alpha1AR subtypes, tamsulosin and naftopidil, in the treatment of benign prostatic hyperplasia (BPH).
PATIENTS AND METHODS: Patients with BPH were randomized to receive either tamsulosin or naftopidil. The primary efficacy variables were the changes in the total International Prostate Symptom Score (IPSS), maximum flow rate on free uroflowmetry, and residual urine volume. The secondary efficacy variables were average flow rate, changes in the IPSS storage score, IPSS voiding score, and quality-of-life (QoL) Index score, from baseline to endpoint (12 weeks). Data on all randomized patients were included in the safety analyses for adverse effects and changes in blood pressure.
RESULTS: Of the 185 patients enrolled data for 144 who were eligible for inclusion in the efficacy analysis were analysed (75 from the tamsulosin and 69 from the naftopidil group). There was no significant difference in any variable at baseline between the groups. There were statistically significant improvements for all primary and secondary variables in both groups, except for residual urine in the tamsulosin group. However, there was no significant intergroup difference in the improvement of any efficacy variable between the groups. The adverse effects were comparable, with no significant differences in systolic and diastolic blood pressure after treatment in both groups.
CONCLUSIONS: This study suggests that naftopidil is as effective and safe as tamsulosin. Both drugs were effective in improving storage and voiding symptoms. However, there was no difference in clinical efficacy or adverse effects between the alpha1 AR antagonists with different affinity to alpha1 subtypes, alpha1a and alpha1d.

PMID 16104914  BJU Int. 2005 Sep;96(4):581-6. doi: 10.1111/j.1464-410X・・・
著者: K Shibata, R Foglar, K Horie, K Obika, A Sakamoto, S Ogawa, G Tsujimoto
雑誌名: Mol Pharmacol. 1995 Aug;48(2):250-8.
Abstract/Text alpha 1-Adrenoceptors (ARs) comprise a heterogeneous family, and subtype-selective ligands are valuable for studying the functional role of each receptor subtype. We characterized a newly synthesized, alpha 1-AR antagonist, KMD-3213, by using Chinese hamster ovary cells stably expressing the three cloned human alpha 1-ARs (alpha 1a, alpha 1b, and alpha 1d), as well as native rat and human tissues. KMD-3213 potently inhibited 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but had 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively. KMD-3213 inhibited norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs. Using pharmacologically well characterized native rat tissues [submaxillary gland (alpha 1A-AR-expressing tissue), liver (alpha 1B-AR-expressing tissue), and heart (mixed alpha 1A- and alpha 1B-AR-expressing tissue)], binding studies showed that inhibition curves for KMD-3213 in submaxillary gland and liver best fit a one-site model (with Ki values of 0.15 and 16 nM, respectively), whereas KMD-3213 had high and low affinity sites in heart membranes. Chloroethylclonidine treatment of rat heart membranes completely eliminated the low affinity sites for KMD-3213. Furthermore, in human liver and prostate KMD-3213 could identify high and low affinity sites, the Ki values of which corresponded well to those for the cloned human alpha 1a- and alpha 1b-ARs, respectively. Moreover, the affinity of KMD-3213 was found to be approximately 10-fold higher at the cloned human alpha 1a-AR than at the cloned rat alpha 1a-AR. KMD-3213 is a potent and highly selective antagonist for the human alpha 1a-AR and would be useful for studying the physiological roles of human alpha 1-AR subtypes.

PMID 7651358  Mol Pharmacol. 1995 Aug;48(2):250-8.
著者: Leonard S Marks, Marc C Gittelman, Lawrence A Hill, Weining Volinn, Gary Hoel
雑誌名: J Urol. 2009 Jun;181(6):2634-40. doi: 10.1016/j.juro.2009.02.034. Epub 2009 Apr 16.
Abstract/Text PURPOSE: We evaluated the efficacy and safety of silodosin for treatment of benign prostatic hyperplasia symptoms in 2 randomized, placebo controlled, phase 3 studies.
MATERIALS AND METHODS: Men 50 years or older with an International Prostate Symptom Score of 13 or greater and peak urinary flow rate of 4 to 15 ml per second received placebo or 8 mg silodosin daily with breakfast for 12 weeks. The primary end point was International Prostate Symptom Score change from baseline to last observation. Change in peak urinary flow rate was a secondary end point. Differences in treatment efficacy were assessed by ANCOVA.
RESULTS: Of 923 patients (mean age 65 years) 466 received silodosin and 457 placebo. After 0.5 week (range 3 to 4 days) of treatment patients receiving silodosin vs placebo achieved significant improvement in total International Prostate Symptom Score (difference -1.9, p <0.0001) and irritative (-0.5, p = 0.0002) and obstructive (-1.4, p <0.0001) subscores. The mean +/- SD change from baseline in total International Prostate Symptom Score was -4.2 +/- 5.3 for silodosin vs -2.3 +/- 4.4 for placebo. Differences (silodosin vs placebo) in International Prostate Symptom Score and subscores increased by week 12 (p <0.0001). Mean change from baseline in peak urinary flow rate (ml per second) 2 to 6 hours after initial dose was greater (p <0.0001) with silodosin (2.8 +/- 3.4) than placebo (1.5 +/- 3.8). Differences remained significant (p <0.001) through week 12. The most common treatment emergent adverse event was (mostly mild) retrograde ejaculation (silodosin 28.1% of patients, placebo 0.9%). Few patients receiving silodosin (2.8%) discontinued because of retrograde ejaculation. Proportions of patients with treatment emergent orthostatic hypotension were similar for silodosin (2.6%) and placebo (1.5%).
CONCLUSIONS: Treatment with silodosin produced rapid improvement in urinary symptoms that was sustained for 12 weeks. Silodosin was well tolerated with a low incidence of orthostatic hypotension.

PMID 19371887  J Urol. 2009 Jun;181(6):2634-40. doi: 10.1016/j.juro.20・・・
著者: Taiji Tsukamoto, Yukihiro Endo, Michiro Narita
雑誌名: Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-2042.2009.02357.x. Epub 2009 Aug 5.
Abstract/Text OBJECTIVES: To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia (BPH).
METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study. A total of 378 subjects with clinical BPH having an International Prostate Symptom Score (IPSS) of 8 points or greater, a prostate volume of 30 mL or greater, and a maximal urinary flow rate (Qmax) of 15 mL/s or less were randomized to receive placebo or dutasteride once daily for 52 weeks. Subjects were stratified according to tamsulosin use at baseline. The numbers of subjects with and without tamsulosin use were 242 and 136, respectively. IPSS, Qmax, prostate volume and drug safety were evaluated.
RESULTS: Continued improvement in IPSS was noted in the dutasteride group, and dutasteride significantly decreased IPSS compared with placebo. At week 52, dutasteride significantly improved Qmax and prostate volume compared with placebo. Drug-related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting.
CONCLUSIONS: Dutasteride improves urinary symptoms and flow rate and reduces prostate volume. In Japanese men with BPH, it is effective and generally well tolerated during the one-year treatment period.

PMID 19674165  Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-・・・
著者: Claus G Roehrborn, Peter Boyle, J Curtis Nickel, Klaus Hoefner, Gerald Andriole, ARIA3001 ARIA3002 and ARIA3003 Study Investigators
雑誌名: Urology. 2002 Sep;60(3):434-41.
Abstract/Text OBJECTIVES: To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II.
METHODS: A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments.
RESULTS: At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated.
CONCLUSIONS: Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.

PMID 12350480  Urology. 2002 Sep;60(3):434-41.
著者: Claus G Roehrborn, Paul Siami, Jack Barkin, Ronaldo Damião, Kim Major-Walker, Indrani Nandy, Betsy B Morrill, R Paul Gagnier, Francesco Montorsi, CombAT Study Group
雑誌名: Eur Urol. 2010 Jan;57(1):123-31. doi: 10.1016/j.eururo.2009.09.035. Epub 2009 Sep 19.
Abstract/Text BACKGROUND: Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement.
OBJECTIVE: To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression.
DESIGN, SETTING, AND PARTICIPANTS: The Combination of Avodart and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men > or =50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score > or =12, prostate volume > or =30 cm(3), prostate-specific antigen 1.5-10 ng/ml, and maximum urinary flow rate (Q(max)) >5 and < or =15 ml/s with minimum voided volume > or =125 ml.
INTERVENTION: Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both.
MEASUREMENTS: The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability.
RESULTS AND LIMITATIONS: Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation.
CONCLUSIONS: The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. CLINICALTRIALS.GOV IDENTIFIER: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

PMID 19825505  Eur Urol. 2010 Jan;57(1):123-31. doi: 10.1016/j.eururo.・・・
著者: J Barkin, M Guimarães, G Jacobi, D Pushkar, S Taylor, O B van Vierssen Trip
雑誌名: Eur Urol. 2003 Oct;44(4):461-6.
Abstract/Text OBJECTIVES: The Symptom Management After Reducing Therapy (SMART-1) study examined the combination of the dual action 5alpha-reductase inhibitor (5ARI) dutasteride, and alpha(1)-blocker tamsulosin, followed by withdrawal of tamsulosin in men with symptomatic BPH.
METHODS: 327 BPH patients were randomised to 0.5mg dutasteride and 0.4 mg tamsulosin for 36 weeks (DT36) or 0.5 mg dutasteride and 0.4 mg tamsulosin for 24 weeks followed by dutasteride and tamsulosin matched placebo for the remaining 12 weeks (DT24+D12). Patients' assessment of their symptoms, IPSS at weeks 24, 30, and drug safety were evaluated.
RESULTS: 77% of DT24+D12 patients felt the same/better at week 30 compared with week 24 (changes in IPSS were consistent with this finding). Of those subjects with an IPSS <20 who changed to dutasteride monotherapy at week 24, 84% switched without a noticeable deterioration in their symptoms. In the 27% of men with severe baseline symptoms (IPSS >or=20) who had withdrawal of tamsulosin therapy at week 24, 42.5% reported a worsening of their symptoms compared with 14% in the DT36 group. The regimens were well tolerated.
CONCLUSIONS: Dutasteride can be used in a 24-week combination with tamsulosin, to achieve rapid onset of symptom relief in patients at risk of underlying disease progression. This symptom relief is maintained in the majority of patients after the alpha(1)-blocker is removed from the combination. Patients with severe symptoms may benefit from longer-term combination therapy.

PMID 14499682  Eur Urol. 2003 Oct;44(4):461-6.
著者: John D McConnell, Claus G Roehrborn, Oliver M Bautista, Gerald L Andriole, Christopher M Dixon, John W Kusek, Herbert Lepor, Kevin T McVary, Leroy M Nyberg, Harry S Clarke, E David Crawford, Ananias Diokno, John P Foley, Harris E Foster, Stephen C Jacobs, Steven A Kaplan, Karl J Kreder, Michael M Lieber, M Scott Lucia, Gary J Miller, Mani Menon, Douglas F Milam, Joe W Ramsdell, Noah S Schenkman, Kevin M Slawin, Joseph A Smith, Medical Therapy of Prostatic Symptoms (MTOPS) Research Group
雑誌名: N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.
Abstract/Text BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.
METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.
RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.
CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

Copyright 2003 Massachusetts Medical Society
PMID 14681504  N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056・・・
著者: B-H Chung, C G Roehrborn, P Siami, K Major-Walker, B B Morrill, T H Wilson, F Montorsi
雑誌名: Prostate Cancer Prostatic Dis. 2009;12(2):152-9. doi: 10.1038/pcan.2008.49. Epub 2008 Sep 23.
Abstract/Text Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this double-blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. Decrease in international prostate symptom score (IPSS) at month 24 from baseline (the primary endpoint) was significantly greater with combination treatment compared with tamsulosin (P<0.05), and numerically, but not statistically significantly, greater compared with dutasteride. Mean IPSS was reduced from baseline by 7.5 (+/-0.84) in the combination group, by 6.3 (+/-0.86) in the dutasteride group and by 4.5 (+/-0.78) in the tamsulosin group, resulting in respective mean IPSS at months 24 of 11.4 (+/-0.60), 12.7 (+/-0.70) and 14.3 (+/-0.74). The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy.

PMID 18813219  Prostate Cancer Prostatic Dis. 2009;12(2):152-9. doi: 1・・・
著者: Osamu Nishizawa, Osamu Yamaguchi, Masayuki Takeda, Osamu Yokoyama, TAABO Study Group
雑誌名: Low Urin Tract Symptoms. 2011 Apr;3(1):29-35. doi: 10.1111/j.1757-5672.2010.00081.x. Epub 2010 Sep 20.
Abstract/Text OBJECTIVES: TAABO was a randomized, controlled trial to evaluate the efficacy and safety of combination therapy of tamsulosin (TAM) with propiverine (PROP) in men with both benign prostatic hyperplasia and overactive bladder.
METHODS: It enrolled men 50 years or older who had an international prostate symptom score (IPSS) of 8 or higher, an urgency item score of 1 or higher, and a quality of life (QOL) score of 2 or higher. After 8 weeks of TAM 0.2 mg/day, patients who met the inclusion criteria (8 micturitions per 24 h and 1 urgency per 24 h, evaluated by bladder diary) and were eligible for 12-weeks of continued Treatment II. Five hundred and fifteen patients were enrolled. Thereafter, 214 patients were assigned randomly to receive either TAM alone (n = 67), TAM plus PROP 10 mg (n = 72), or TAM plus PROP 20 mg (n = 75) in Treatment II. The primary efficacy end point was a change in micturitions per 24 h documented in the bladder diary. The change from baseline in urgency episodes per 24 h, IPSS, IPSS/QOL subscore, urinary flow rate and postvoid residual volume were assessed as secondary efficacy measures.
RESULTS: A total of 141 men (47 TAM, 49 TAM plus PROP 10 mg, and 45 TAM plus PROP 20 mg patients) were assessed by week 12. Compared with the TAM, TAM plus PROP 10 mg patients experienced significantly fewer micturitions (P = 0.0261), urgencies (P = 0.0093) per 24 h, lower IPSS storage (P = 0.0465), and IPSS urgency (P = 0.0252) subscores.
CONCLUSIONS: These results suggest that combining TAM and 10 mg of PROP for 12 weeks provides added benefit for men with both benign prostatic hyperplasia and overactive bladder.

© 2010 Blackwell Publishing Asia Pty Ltd.
PMID 26676349  Low Urin Tract Symptoms. 2011 Apr;3(1):29-35. doi: 10.1・・・
著者: Claus G Roehrborn, Steven A Kaplan, J Stephen Jones, Joseph T Wang, Tamara Bavendam, Zhonghong Guan
雑誌名: Eur Urol. 2009 Feb;55(2):472-9. doi: 10.1016/j.eururo.2008.06.032. Epub 2008 Jun 17.
Abstract/Text BACKGROUND: Some men with lower urinary tract symptoms (LUTS) including overactive bladder (OAB) symptoms may benefit from antimuscarinic therapy, with or without an alpha-adrenergic antagonist.
OBJECTIVES: To evaluate the safety and efficacy of tolterodine extended release (ER), tamsulosin, or tolterodine ER+tamsulosin in men meeting symptom entry criteria for OAB and prostatic enlargement trials, stratified by prostate size.
DESIGN, SETTING, AND PARTICIPANTS: Subjects with an International Prostate Symptom Score (IPSS) >or=12; frequency and urgency, with or without urgency urinary incontinence; postvoid residual volume (PVR) <200 mL; and maximum urinary flow rate (Q(max)) >5 mL/s were randomized to receive placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER+tamsulosin for 12 wk. Data were stratified by median baseline prostate volume (<29 mL vs >or=29 mL).
MEASUREMENTS: Endpoints included week 12 changes in bladder diary variables, IPSS scores, and safety variables.
RESULTS AND LIMITATIONS: Among men with larger prostates, tolterodine ER+tamsulosin significantly improved frequency (p=0.001); urgency (p=0.006); and IPSS total (p=0.001), storage (p<0.001), and voiding scores (p<0.013). Tamsulosin significantly improved IPSS voiding scores (p=0.030). Among men with smaller prostates, tolterodine ER significantly improved frequency (p=0.016), UUI episodes (p=0.036), and IPSS storage scores (p=0.005). Tolterodine ER+tamsulosin significantly improved frequency (p=0.001) and IPSS storage scores (p=0.018). Tamsulosin significantly improved nocturnal frequency (p=0.038) and IPSS voiding (p=0.036) and total scores (p=0.044). There were no clinically or statistically significant changes in Q(max) or PVR; incidence of acute urinary retention (AUR) was low in all groups (CONCLUSIONS: Men with smaller prostates and moderate-to-severe LUTS including OAB symptoms benefited from tolterodine ER. Therapy with tolterodine ER+tamsulosin was effective regardless of prostate size. Tolterodine ER, with or without tamsulosin, was well tolerated and not associated with increased incidence of AUR.

PMID 18583022  Eur Urol. 2009 Feb;55(2):472-9. doi: 10.1016/j.eururo.2・・・
著者: Teruhiko Yokoyama, Katsutoshi Uematsu, Toyohiko Watanabe, Katsumi Sasaki, Hiromi Kumon, Atsushi Nagai, Okayama Urological Research Group
雑誌名: Scand J Urol Nephrol. 2009;43(4):307-14. doi: 10.1080/00365590902836740.
Abstract/Text OBJECTIVE: To assess the efficacy and safety of propiverine hydrochloride (antimuscarinic), naftopidil (alpha(1)-adrenoceptor antagonist) or both in patients with male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia and concomitant overactive bladder (OAB).
MATERIAL AND METHODS: Men aged at least 50 years who had a total International Prostate Symptom Score (IPSS) of 8 or higher and bladder dairy documenting micturition frequency (more than eight micturitions/24 h) and urgency (more than one episode/24 h), with or without urgency urinary incontinence were randomized into three groups: group N, naftopidil (50 mg once daily) only; group P, propiverine hydrochloride (20 mg once daily); and group NP, naftopidil (50 mg once daily) plus propiverine hydrochloride (20 mg once daily) for a 4-week treatment regimen.
RESULTS: A total of 66 men, including 20 in group N, 23 in group P and 23 in group NP, were treated and 58 (87.9%) completed the 4 weeks of treatment. IPSS improved significantly in groups N and NP. Urinary frequency improved significantly in groups P and NP. Postvoid residual urine volume increased significantly in groups P and NP. Significant improvements in urgency episodes were noted in each group. One patient in group P required catheterization owing to acute urinary retention and another stopped medication because of difficulty in voiding.
CONCLUSION: These results suggest that each treatment showed effectiveness for male LUTS with OAB. However, there are some possibilities of adverse effects with propiverine hydrochloride monotherapy.

PMID 19396723  Scand J Urol Nephrol. 2009;43(4):307-14. doi: 10.1080/0・・・
著者: A Athanasopoulos, K Gyftopoulos, K Giannitsas, J Fisfis, P Perimenis, G Barbalias
雑誌名: J Urol. 2003 Jun;169(6):2253-6. doi: 10.1097/01.ju.0000067541.73285.eb.
Abstract/Text PURPOSE: We evaluate the effect of tolterodine combined with tamsulosin on quality of life in patients with bladder outlet obstruction and concomitant detrusor instability.
MATERIALS AND METHODS: The study included 50 consecutive patients with urodynamically proven mild or moderate bladder outlet obstruction and concomitant detrusor instability. All patients were initially treated with 0.4 mg. tamsulosin orally once a day. A week later the patients were randomly allocated into group 1-25 who continued treatment with tamsulosin only and, group 2-25 who also received 2 mg. tolterodine orally twice daily. Reevaluation with a quality of life questionnaire and urodynamic study was performed after 3 months.
RESULTS: Two patients from group 2 stopped tolterodine while 1 patient from each group stopped tamsulosin because of hypotension. Analysis revealed statistically significant improvement in quality of life scores only in group 2 patients (mean score 525.0 and 628.4 before and after treatment, respectively, 2-sided t test p = 0.0003). A significant difference was noted in both groups after treatment for maximum flow rate and volume at first contraction. Additionally, in group 2, a statistically significant difference was observed for maximum detrusor pressure and maximum unstable contraction pressure after treatment.
CONCLUSIONS: Combination treatment with an alpha-blocker (tamsulosin) plus an anticholinergic (tolterodine) improves quality of life in patients with bladder outlet obstruction and concomitant detrusor instability. Interestingly, no acute urinary retention was observed and tolterodine did not affect the quality of urine flow or residual urine volume. The proposed combination appears to be an effective and relatively safe treatment option in patients with bladder outlet obstruction and detrusor instability.

PMID 12771763  J Urol. 2003 Jun;169(6):2253-6. doi: 10.1097/01.ju.0000・・・
著者: L Cardozo, M Lisec, R Millard, O van Vierssen Trip, I Kuzmin, T E Drogendijk, M Huang, A M Ridder
雑誌名: J Urol. 2004 Nov;172(5 Pt 1):1919-24.
Abstract/Text PURPOSE: In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin.
MATERIALS AND METHODS: The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition.
RESULTS: Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo).
CONCLUSIONS: In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.

PMID 15540755  J Urol. 2004 Nov;172(5 Pt 1):1919-24.
著者: F Haab, L Cardozo, C Chapple, A M Ridder, Solifenacin Study Group
雑誌名: Eur Urol. 2005 Mar;47(3):376-84. doi: 10.1016/j.eururo.2004.11.004. Epub 2005 Jan 5.
Abstract/Text OBJECTIVE: To examine safety and tolerability findings as primary endpoints, and efficacy outcomes as secondary endpoints, of solifenacin treatment over a period of up to 1 year. Long-term efficacy in the treatment of overactive bladder (OAB) syndrome depends in part on the patient's persistence with pharmacologic therapy. Agents with a favourable therapeutic index supporting high levels of patient satisfaction and persistence are needed.
METHODS: The present study was a 40-week open-label extension of two 12-week, placebo-controlled, double-blind studies of solifenacin treatment in patients with OAB. Patients who completed the 12-week studies were offered participation in the open-label extension study. All patients who entered the open-label extension study initially received solifenacin 5 mg daily for 4 weeks, after which a flexible dosing regimen allowed patients to individualise their treatment (5 mg or 10 mg) at each of the 3 study visits. Safety and tolerability assessments (the primary variable) included adverse event reporting. Efficacy data were collected from micturition diaries completed at weeks 16, 28, 40, and 52.
RESULTS: Ninety-one percent (1637/1802) of patients who completed the two 12-week randomised studies chose to participate in the long-term open-label extension study. A total of 81% of patients completed 40 weeks of open-label treatment. Solifenacin treatment was safe and well tolerated, and rates of anticholinergic side effects were relatively low. Only 4.7% of patients discontinued treatment owing to adverse events. Improvements in major symptoms of OAB were noted for all patients for up to 52 weeks of treatment. In patients randomised to solifenacin in the double-blind studies, there were small incremental improvements in all efficacy parameters (reductions in episodes per 24 hours of urgency, reductions in frequency and urge incontinence, and increases in volume voided per micturition) over the course of the extension study. Efficacy was confirmed when outcomes were assessed as a function of total solifenacin exposure. Patient satisfaction with solifenacin tolerability (85%) and efficacy (74%) were high. These results indicate that long-term treatment with solifenacin was well tolerated and associated with improvements in efficacy parameters based on patient diary data recorded over the 12-month treatment period. Moreover, the high level of patient satisfaction reported appeared to correlate well with the quantified improvements in key symptoms demonstrated in this study.
CONCLUSIONS: Long-term therapy with solifenacin resulted in a favourable tolerability profile, and was associated with improvements in efficacy parameters based on diary data recorded over a 12-month period. This balance of tolerability and efficacy with solifenacin was associated with excellent persistence with therapy. These results suggest that solifenacin may be useful for the long-term treatment of the chronic symptoms associated with OAB.

PMID 15716204  Eur Urol. 2005 Mar;47(3):376-84. doi: 10.1016/j.eururo.・・・
著者: Alan D Garely, Vincent Lucente, Jonathan Vapnek, Neila Smith
雑誌名: Ann Pharmacother. 2007 Mar;41(3):391-8. doi: 10.1345/aph.1H581. Epub 2007 Mar 6.
Abstract/Text BACKGROUND: Approximately one-third of patients with overactive bladder (OAB) experience incontinence, a bothersome symptom with a clear negative effect on quality of life.
OBJECTIVE: To assess OAB patients' perceptions of improvements in symptom bother and quality of life after taking solifenacin under conditions reflecting day-to-day practice.
METHODS: VOLT (the VESIcare Open-Label Trial) was a prospective, open-label study in patients with OAB (defined as urgency, urge urinary incontinence, daytime frequency, or nocturia for > or =3 mo) who were treated with flexibly dosed, once-daily solifenacin for 12 weeks. This study included subjects enrolled in VOLT who, at baseline, had urge incontinence and reported incontinence as their most bothersome symptom. All patients were started on solifenacin 5 mg/day; at week 4, the dosage could be increased to 10 mg/day and at week 8 could be maintained or decreased back to 5 mg/day. Efficacy was assessed by 3 independent patient-reported outcomes: the Patient Perception of Bladder Condition (PPBC) scale, a visual analog scale (VAS) for assessing individual symptoms, and the Overactive Bladder Questionnaire (OAB-q).
RESULTS: Of the 2205 patients in the VOLT full analysis set, 1586 (71.9%) had urge incontinence at baseline, of which 582 (36.7%) reported incontinence as their most bothersome symptom. In this cohort, mean PPBC score at baseline was 4.6 (indicating moderate-to-severe problems) and at endpoint had decreased significantly to 2.9 (very minor to some minor problems; p < 0.001). At endpoint, 80.4% of patients achieved improvement in their PPBC score. These patients reported significant improvements from baseline in urinary urgency, urge incontinence, frequency, and nocturia on the VAS (p < 0.001) and all OAB-q domains (symptom severity, coping, concern, sleep, social, health-related quality of life) at endpoint (p < 0.001).
CONCLUSIONS: Patients reporting urge incontinence as their most bothersome OAB symptom can be expected to demonstrate significant improvements in multiple patient-related outcomes following treatment with flexibly dosed solifenacin.

PMID 17341526  Ann Pharmacother. 2007 Mar;41(3):391-8. doi: 10.1345/ap・・・
著者: Nobuo Okui
雑誌名: World J Urol. 2019 Nov;37(11):2459-2466. doi: 10.1007/s00345-019-02644-7. Epub 2019 Jan 28.
Abstract/Text PURPOSE: To examine the efficacy and safety of non-ablative vaginal erbium:YAG laser (VEL) for the treatment of overactive bladder syndrome (OAB) compared with those of two other common pharmacotherapies, namely, anticholinergics and β3-adrenoceptor agonists.
METHODS: Female subjects aged 60-69 years who presented with symptoms of OAB from 2015 to 2017 were assigned to three groups (n = 50) receiving treatment with an anticholinergic agent (4 mg fesoterodine), a β3-adrenoceptor agonist (25 mg mirabegron), or VEL (20 min/session of VEL performed thrice). The OAB symptom score (OABSS), Vaginal Health Index Scale (VHIS), and occurrence of adverse effects were examined prior to and at 1 year following treatment initiation.
RESULTS: The three groups showed significant improvement (p < 0.001) for all items of the OABSS questionnaire. Improved VHIS scores were observed only in the VEL group. Furthermore, after VEL treatment, a negative correlation was observed between questions 3 (urinary urgency) and 4 (urgency urinary incontinence) of the OABSS and VHIS. Regarding safety, no adverse events were observed in the VEL group. However, subjects in the other two groups complained of constipation, as indicated by the Constipation Assessment Scale scores, and mouth dryness. The therapeutic effects were inadequate for one and two subjects in the VEL and β3-adrenoceptor agonist groups, respectively.
CONCLUSIONS: VEL safely and effectively improved OABSS through a different mechanism than that involved in pharmacotherapy. We propose the use of VEL as a novel surgical treatment option in the field of urology.

PMID 30687908  World J Urol. 2019 Nov;37(11):2459-2466. doi: 10.1007/s・・・

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