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1 대한배뇨장애요실금학회지 J Korean Continence Soc 2008;12:19-26 원저 비신경인성여성배뇨장애환자에서 4주간의 Doxazosin GITS의효용성과안정성 : 단기추적결과 성균관대학교의과대학비뇨기과학교실, 1 기톨릭대학교의과대학비뇨기과학교실 2 관동대학교의과대학비뇨기과학교실, 3 울산대학교의과대학비뇨기과학교실 이규성 한덕현 김지영 정진우 추설호 김준철 1 서주태 2 주명수 3 Efficacy and Safety of Doxazosin GITS over 4 weeks for the Treatment of Non-neurogenic Voiding Dysfunction in Females: Short-term Outcomes Kyu-Sung Lee, Deok Hyun Han, Ji Young Kim, Jin Woo Chung, Seol Ho Choo, Joon Chul Kim 1, Ju Tae Seo 2, Myung-Soo Choo 3 From the Department of Urology, Sungkyunkwan University School of Medicine, 1 Department of Urology, College of Medicine, Catholic University of Korea, Kangnam St Mary s Hospital, Seoul, 2 Department of Urology, Kwandong University College of Medicine, Cheil General hospital & Women s Healthcare Center 3 Department of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Purpose: We administered doxazosin gastrointestinal therapeutic system (GITS) to women with non-neurogenic voiding dysfunction to evaluate its therapeutic effects. Materials and Methods: Women who had voiding dysfunctions for at least 3 mo were included. Inclusion criteria were age 18yr, an International Prostate Symptom Score (IPSS) 15, and a maximum flow rate (Q max) <15mL/sec and/or postvoid residual (PVR) 150mL. Patients with neurogenic voiding dysfunction or anatomical bladder outlet obstruction were excluded. All patients were classified according to the Blaivas-Groutz nomogram. After 4 weeks, treatment outcomes were evaluated. Results: Sixty-two patients were evaluated of mean age 53.8 (32-78)yr. According to the Blaivas-Groutz nomogram, 24 patients had no or mild obstruction (group A) and 38 had moderate or severe obstruction (group B). After treatment, mean IPSS decreased significantly and by more than 5 points in 42 (67.7%). Mean bother scores, Q max, and PVR also changed significantly. Thirty-seven (59.7%) showed Q max increases of more than 50%. No significant difference were observed between the groups in terms of IPSS, bother score, Q max, PVR, micturition frequencies, or functional bladder capacity changes. Adverse effects related to medication were de novo stress 접수일자 : 2008 년 4 월 15 일, 수정일자 : 2008 년 5 월 24 일, 채택일자 : 2008 년 5 월 30 일교신저자 : 주명수, 서울아산병원비뇨기과, 서울시송파구풍납 2 동 우 Tel: , Fax: , mschoo@amc.seoul.kr Vol. 12, No. 1,

2 이규성 한덕현 김지영 정진우 추설호 김준철 서주태 주명수 urinary incontinence (SUI) (1 case) and underlying SUI aggravation (1 case). By satisfaction assessments, 16 patients (25.8%) were 'mainly satisfied', 31 (50%) were 'slightly satisfied', and 15 (24.2%) were 'dissatisfied'. Conclusion: Doxazosin GITS was found to be effective in female patients with voiding dysfunction regardless of obstruction grade. The α-adrenoceptor antagonists should be viewed as initial treatment option for women with a non-neurogenic voiding dysfunction. (J Korean Continence Soc 2008;12:19-26) Key Words: Urinary bladder neck obstruction, Female, Alpha-adrenergic receptor blockers, Outcome assessment 서 론 뇨장애에서알파1 아드레날린차단제의치료효과에대해평가하고자하였다. 알파아드레날린차단제는전립선비대증과관련된하부요로증상을호소하는환자들에게처음사용되었다. 이후연구들에의해알파아드레날린차단제는하부요로증상을가진남성들에서효용성과내약성이증명되어지금은일차치료제로널리사용되고있지만여성에있어서의효과는거의연구된바없다. 여성배뇨장애는배뇨근의수축이효과적이지못한경우, 방광출구폐색이있는경우, 배뇨-괄약근협조장애가있는경우, 또는이런원인들이병합되어방광을충분히비우기힘든상태를말하며, 하부요로증상을호소하는여성의 2%-25.5% 에서이러한배뇨장애가있는것으로알려져있다 (1). 최근의연구들은기능적방광출구폐색또는배뇨근저활동성이있는여성들에서알파1 아드레날린차단제가증상과배뇨지표들을효과적으로개선시킴을보여주고있다 (2-4). 알파1 아드레날린은방광경부와외요도괄약근을포함해여러부위에서중요한역할을하므로, 알파1 아드레날린차단제가여성의배뇨장애에이용될수있을것이라고추론할수있다 (5-8). 그러나여성배뇨장애에서알파1 아드레날린차단제가효과적이라는임상적증거는많지않은실정이다. 저자들은본연구에서 doxazosin gastrointestinal therapeutic system (GITS) 을이용해여성배 대상및방법 1. 대상최소 3개월이상배뇨장애로인한하부요로증상이지속된여성을대상으로하였다. 본연구는전향적, 공개연구로다기관에서진행되었다. 18세이상, 국제전립선증상점수 (IPSS) 15점이상, 최대요속 (Maximal flow rate: Q max) 15 ml/sec 미만, 배뇨후잔뇨 (postvoid residual volume: PVR) 150mL 이상인환자들을대상으로하였으며, 신경인성배뇨장애나, 해부학적으로방광출구폐색의요인이있는경우, 즉요도협착, 방광경부구축, 방광내요석, 방광종양, 심한골반장기탈출증, 이전의요실금수술력, 요도게실등이있는경우는제외하였다. 모든환자에게연구의목적과진행과정을설명하고동의를구했다. 2. 치료및효과의판정모든환자에게 Doxazosin GITS을하루 1회 4mg을 4주간투여하였다. Bethanechol chloride등의콜린성약물이나알파아드레날린차단제등의다른약물은 4주의연구기간동안복용하지못하도록하였다. 치료전모든환자들은 20 대한배뇨장애요실금학회지

3 비신경인성여성배뇨장애환자에서 Doxazosin 의효용성과안정성 문진과골반내진, 신경학적검사, 요검사, 요배양검사, 그리고압력-요류검사를시행하였고, 3일간의배뇨일지를작성하였다. 요역동학검사는국제요실금학회의권장사항에따라시행하였다 (9). 치료결과는 IPSS, 불편점수, Q max, PVR, 배뇨횟수 ( 주간, 야간 ), 기능적방광용적 (Functional bladder capacity: FBC), 그리고환자의주관적만족도를이용해평가하였다. 주관적만족도는매우만족, 만족, 불만족의세단계로나누어분류하였다. 치료에따른부작용도함께조사하였다. 방광출구폐색의정도는 Blaivas-Groutz nomogram을이용하여분류하였고 (10), 폐색의정도에따라두군으로나누었다 (Figure 1). 폐색이없거나경도의폐색이있는환자는 A군으로, 중등도또는중증의폐색이있는경우는 B군으로나누었으며, 두군간의결과를비교하였다. 3. 통계분석 IPSS, Q max, PVR, 총배뇨횟수, 그리고기능적방광용적의치료전, 후의변화를비교시정규분포를따르는항목들은 paired t-test를이용하였고, 정규분포를따르지않는항목들은 Wilcoxon's signed-rank test를이용하여분석하였다. 두군간항목혹은항목의변화정도를비교시정규분포를따르는항목들은 Student's t-test를, 정규분포를따르지않는항목들은 Mann-Whitney test를이용하여분석하였다. 불 Group B Group A Severe obstruction Moderate obstruction Mild obstruction No obstruction Figure 1. Classification of the study subjects using a bladder outlet obstruction nomogram as devised by Blaivas and Groutz; Group A - no obstruction or mild obstruction, Group B - moderate obstruction or severe obstruction. Pdet max: maximum detrusor pressure, FreeQ max: maximum flow rate without catheter insertion. 편점수와주관적인만족도의변화는 non-parametric method 를이용하여분석하였다. p-value는 0.05 미만일때통계적으로의미있는것으로판단하였다 Severe obstruction (n=3; 4.8%) Moderate obstruction (n=35; 56.5% Mild obstruction (n=21; 33.9%) 결 총 64명의환자가포함되었고 4주간의연구기간동안 2 명의환자가탈락하여 62명의환자를대상으로하였다. 환자들의평균나이는 53.8세 (32-78세) 였고, 평균유병기간은 4년 (3개월-30년) 이었다. 주증상은빈뇨 (90.3%), 약뇨 (58.1%), 요절박 (53.2%), 요주저 (38.8%), 잔뇨감 (24.2%), 그리고간헐뇨 (16.1%) 의순이었다. 8명 (12.9%) 의환자에서는경증의복압성요실금이있었다. 15명 (24.2%) 은자궁근종으로자궁절제술을받은과거력이있었다. Blaivas-Groutz 노모그램에따라폐색의정도를나누었을때폐색이없는경우가 3명 (4.8%), 경증의폐색이있는경우가 21명 (33.9%), 중등도의폐색이 35명 (56.5%), 그리고중증의폐색이 3명 (4.8%) 이었다 (Figure 2). 4주간의치료기간이끝난후평균 IPSS는 22.3±5.51에서 14.8±7.74로의미있게감소하였고저장증상과배뇨증상모두향상되었다 (Table 1). 42명 (67.7%) 에서는 IPSS가 5점이상감소하였다. 불편점수역시유의하게감소하였다. Q max 는 10.9±2.53mL/sec에서 15.9±5.72mL/sec로의미있게증가하였고 PVR은 56.4±59.7mL에서 42.0±41.1mL로감소하였다 (P<0.05). 37명 (59.7%) 의환자는 Q max 가 50% 이상증가하였다. 3일간의배뇨일지를분석하였을때, 총배뇨횟수 No obstruction (n=3; 4.8%) Figure 2. Nomogram showing patient distribution according to obstruction severity. Pdet max: maximum detrusor pressure, FreeQ max: maximum flow rate without catheter insertion. 과 Vol. 12, No. 1,

4 이규성 한덕현 김지영 정진우 추설호 김준철 서주태 주명수 와주간뇨의빈도는유의하게감소하였지만야간뇨횟수는변화가없었다 (Table 2). 기능적방광용적은투약후 292.0±91.3mL에서 329.7±76.3mL로유의하게증가하였다. Blaivas-Groutz 노모그램에따른두군간비교시 IPSS, 불편점수, 총배뇨횟수와주간뇨의빈도는 A군에서더좋지 않았으며, 나이, 유병기간, Q max, PVR과야간뇨횟수는두군간에차이가없었다 (Table 3). IPSS, 불편점수, Q max, PVR, 총배뇨횟수, 주간뇨, 야간뇨의빈도, 기능적방광용적은모두백분율변화에차이가없었다 (Figure 3). 주관적만족도의평가에서 16명 (25.8%) 의환자는매우 Table 1. Changes of symptom score and urodynamic parameters Baseline After treatment p-value IPSS (sum) ± ± 7.74 < * Storage symptom 8.10 ± ± 3.96 < Voiding symptom ± ± 4.86 < * Bother score 4.61 ± ± 1.55 < Maximum flow rate (ml/sec) ± ± 5.72 < * Post-void residual (ml) ± ± < * * paired t-test, Wilcoxon signed ranks test, generalized estimating equations method, IPSS: International Prostatic Symptom Score Table 2. Changes of parameters of frequency-volume chart Baseline After treatment p-value * Micturition frequency/24hr 11.6 ± ± 3.2 < Daytime frequency 10.0 ± ± 2.6 < Nocturia 1.6 ± ± FBC (ml) ± ± 76.3 < * Wilcoxon signed ranks test, FBC: functional bladder capacity Table 3. Baseline characteristics of two groups according to severity of obstruction Group A Group B p-value Age (yr) 51.6 ± ± Symptom duration (yr) 5.2 ± ± IPSS (sum) 26.1 ± ± 3.9 < Storage symptom 10.5 ± ± 3.0 < Voiding symptom 15.7 ± ± Bother score 5.0 ± ± Maximum flow rate (ml/sec) 10.8 ± ± Post-void residual (ml) 48.5 ± ± Micturition frequency/24hr 13.3 ± ± Daytime frequency 11.7 ± ± Nocturia 1.7 ± ± FBC (ml) ± ± Group A: no or mild obstruction according to Blaivas-Groutz nomogram, Group B: moderate or severe obstruction according to Blaivas-Groutz nomogram, Student t-test, Mann-Whitney test, FBC: Functional bladder capacity 22 대한배뇨장애요실금학회지

비신경인성여성배뇨장애환자에서 Doxazosin 의효용성과안정성 % IPSS (total) IPSS (voiding) IPSS (storage) 50% 0.0 24% -10.0-20.0-30.0 26% -40.0 p=0.571 Mostly satisfied Satisfied Dissatisfied -50.0 p=0.512 p=0.687 A -60.

0 group A B group B B Figure 4. Subjective satisfaction rates after treatment in (A) all study subjects and in (B) both groups. p: group comparisons of satisfaction rates. % 20.0 10.0 0.0-10.0-20.

5 비신경인성여성배뇨장애환자에서 Doxazosin 의효용성과안정성 % IPSS (total) IPSS (voiding) IPSS (storage) 50% % % p=0.571 Mostly satisfied Satisfied Dissatisfied p=0.512 p=0.687 A group A A group B Group A p=0.555 Group B % 100 Qmax PVR 80.0 p= p=0.140 Mostly satisfied Satisfied Dissatisfied Mostly satisfied Satisfied Dissatisfied 0.0 group A B group B B Figure 4. Subjective satisfaction rates after treatment in (A) all study subjects and in (B) both groups. p: group comparisons of satisfaction rates. % Toal void/24hr Diurnal void Nocturnal void FBC p=0.384 p=0.563 group A C p=0.507 group B p=0.507 Figure 3. Comparisons of changes in clinical parameters. (A) IPSS, (B) Q max and PVR, (C) micturition frequency and FBC. Values are adjusted using baseline values as covariates. White bars represent group A and black bars groupb. IPSS: International Prostate Symptom Score, Q max: maximum flow rate, PVR: postvoid residual, FBC: functional bladder capacity, p: group comparisons of improvement rates after treatment. 만족이라고대답했고, 31명 (50%) 은만족, 15명 (24.2%) 는불만족이라고대답했다. 만족도의비율은두군간에차이가없었다 (Figure 4). 약물복용과관련된부작용으로는한명의환자에서새롭게복압성요실금이발생하였고, 한명은기존의복압성요실금이악화되었다. 투약에의한다른심각한부작용은발견되지않았고, 이로인해치료가중단된환자는없었다. 고찰본연구결과로알수있듯이알파1 아드레날린차단제인 doxazosin은비신경인성배뇨장애가있는여성에서 IPSS, 불편점수, Q max, PVR, 주간빈뇨, 그리고기능적방광용적에효과를가지고있었다. 또한삶의질향상에도기여를하였고, 대다수의환자들이치료에만족하였다. Vol. 12, No. 1,

6 이규성 한덕현 김지영 정진우 추설호 김준철 서주태 주명수 많은비뇨기과의사들이여성배뇨장애에서알파1 아드레날린차단제를경험적으로사용하고있지만, 그효용성에대해서는거의알려진바가없다. 이는아마도여성배뇨장애의기전에대해거의알려진바가없으며, 표준화된진단기준이나치료방침이없기때문일것이다. 여러연구들이여성배뇨장애의치료에있어알파아드레날린차단제를고려해볼수있는이유를제시하고있다. 동물실험에서남성과여성의요도에알파1 아드레날린수용체의밀도와친화력이비슷함을보여주고있다 (6,8). Nasu 등 (7) 은 RNAse protection assay와 in situ hybridization 을통해사람의근위부요도에서알파1 아드레날린수용체아형들의비율과요도에서의위치를연구하였다. 이연구에서알파1A mrna는남성과여성모두의요도에서 predominant 한아형이며, 알파1D mrna는여성의요도에만존재한다고보고하였고, in situ hybridization 연구에서는요도단면에서의분포에있어각아형간에차이가없다고보고하였다. 이는남성과여성모두에서비슷한알파1 아드레날린기전이요도의 tone을조절한다는것을의미하며, 여성에서도알파1 아드레날린차단제가배뇨중요도저항을줄여줄수있으므로여성배뇨장애에서알파1 아드레날린차단제의사용을고려해볼수있는타당한이유를제시해준다. 이전의연구에서여성의경직성외요도괄약근에대한비선택적알파아드레날린차단제인 phenoxybenzamine의효과에대해보고하였는데, 저자들은 phenoxybenzamine 투약으로증상이거의소실되었으며, 파도형의지리한요속곡선이거의정상화되었다고하였다 (11). 몇몇임상연구보고에서도역시알파아드레날린차단제가방광출구폐색이나신경인성방광을가진여성에서요속을증가시키고 PVR을감소시킨다고하였다 (12,13). Reitz 등 (14) 은선택적알파1A 아드레날린차단제인 tamsulosin이 in vivo에서건강한여성의평균요도내압과최대요도폐쇄압을감소시키는이완효과가있다고보고하였다. 알파1 아드레날린차단제의어떤아형이배뇨기능을호전시키는데더효과적인지는아직명확하지않으며, 여성에서의적정용량또한확립되지않았다. 비선택적알파1 아드레날린차단제인 Doxazosin은전립선비대증이있는남성에게많이처방되고있고, 요속, 배뇨근압, 배뇨시간, 요도저항등을효과적으로개선시킴이이중맹검연구를통해밝혀져있다 (15). 최근의한연구에서는소아에서의배뇨장애와요폐에서 doxazosin이 PVR을유의하게감소시킨 다는보고도있었다 (16). Doxazosin GITS는서방형제제로기존의제제와비교하였을때증상이나요속개선효과가비슷한것으로알려져있다 (17). Doxazosin GITS는용량적정이필요없으며, 첫투여시부작용의빈도가기존의제제보다적은것으로알려져있기때문에 (18), 저자들은 4mg의 doxazosin GITS를사용하였다. 최근의연구들은기능적방광출구폐색을가진여성환자에서알파아드레날린차단제의효과를보고하고있다. Kumar 등 (19) 은기능적방광출구폐색이있는여성의 50% 에서알파아드레날린차단제단독요법이증상과, Q max, PVR을개선시켰다고보고하였다. 그러나나머지 50% 의환자에서는효과가없어서방광경부절개술을시행하거나청결간헐도뇨를지속했다고하였다. Pischedda 등 (3) 도역시여성기능적방광출구폐색환자에서알파1 아드레날린차단제의효용성에대해보고하였는데, 다음과같은진단기준을설정하였다 : Q max < 12mL/s일때, Q max 에서배뇨근의압력 > 40cmH 2O일때, 근전도상외요도괄약근의활동이없을때, 방사선투시검사상방광경부의부적절한 funneling, 정상적인요도직경을가질때, 그리고 PVR = 60mL 일때등이그것이다. 이연구에서는 Tamsulosin을 1개월간투여후 56% 의환자에서증상과 Q max, 그리고 PVR의개선을보였다고하였다. 배뇨근저활동성에서알파아드레날린차단제의효용성에대한연구는많지않다. Yamanish 등 (4) 은배뇨근저활동성을가진여성환자에서 4주간의알파아드레날린차단제투여후총 IPSS 점수가 14.7점에서 8.4점으로감소하였다고하였고, 저장증상점수와배뇨증상점수또한감소하였다고하였다. PVR은 135mL에서 87mL로역시유의하게감소하였다. 기능적방광경부폐색과배뇨근저활동성에대한진단기준이아직명확하지않기때문에압력-요류검사를포함한요역동학검사와필요시방사선투시검사를병행하는것이방광과요도의기능평가에필수적이다 (1,2,4). 그러나이러한검사들은하부요로증상과약한요속을호소하는여성환자들에게일률적으로시행하기에는상당히침습적이라고생각한다. 이번연구에서는 IPSS, 불편점수, Q max, PVR, 배뇨횟수, 그리고기능적방광용적이 doxazosin 치료후에유의하게호전되는것을알수있었고, 폐색의정도에관계없이비슷한변화를가져옴을보여주었다. 따라서여성 24 대한배뇨장애요실금학회지

7 비신경인성여성배뇨장애환자에서 Doxazosin 의효용성과안정성 배뇨장애환자에서알파1 아드레날린차단제의사용은적절한선택이될것이며, 이는배뇨근의수축에관계없이배뇨중요도저항을감소시키기때문일것이라생각된다. 저자들의경우 42명 (68%) 에서 IPSS가 5점이상감소하였고, 37명 (60%) 에서 Q max 가 50% 이상감소하였으며, 부작용은거의없었다. 따라서여성배뇨장애환자의치료적접근에있어압력- 요류검사와방사선투시검사등과같은침습적인검사나청결간헐도뇨혹은방광경부절개등의침습적인치료방법을고려하기전에알파아드레날린차단제의사용을먼저시도해보는것이좋을것으로생각된다. 본연구는몇가지제한점이있다. 첫째, 위약대조연구가아닌관찰연구이기때문에증상점수와주관적만족도에위약효과의영향을배제할수없다. 둘째, 치료기간과추적기간이짧았기때문에장기적인효과를알수없었고, 마지막으로폐색이없는환자와중증의폐색이있는환자가각 3명밖에되지않아환자군의다양성이부족하다는점이다. 따라서여성배뇨장애환자에서알파1 아드레날린차단제의효용성을결정하기위해서는장기적인무작위위약대조실험이필요할것이다. 결론 Doxazosin GITS는여성배뇨장애환자에서효과적인치료방법이며, 방광출구폐색의정도에관계없이효과적이었다. 대부분의환자들이주관적인증상과객관적인지표의호전을보였으며, 치료에만족하는것으로나타났다. 본연구를통하여여성비신경인성배뇨장애환자에서알파1 아드레날린차단제를초기치료방법으로고려할수있을것으로판단되었다. References 1) Groutz A, Blaivas JG. Non-neurogenic female voiding dysfunction. Curr Opin Urol 2002;12: ) Kessler TM, Studer UE, Burkhard FC. The effect of terazosin on functional bladder outlet obstruction in women: a pilot study. J Urol 2006;176: ) Pischedda A, Pirozzi Farina F, Madonia M, Cimino S, Morgia G. Use of alpha1-blockers in female functional bladder neck obstruction. Urol Int 2005;74: ) Yamanishi T, Yasuda K, Kamai T, Tsujii T, Sakakibara R, Uchiyama T, et al. Combination of a cholinergic drug and an alpha-blocker is more effective than monotherapy for the treatment of voiding difficulty in patients with underactive detrusor. Int J Urol 2004;11: ) Andersson KE, Lepor H, Wyllie MG. Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate 1997;30: ) Morita T, Latifpour J, O'Hollaren B, Wheeler MA, Weiss RM. Sex differences in function and distribution of alpha 1- and alpha 2-adrenoceptors in rabbit urethra. Am J Physiol 1987;252:F ) Nasu K, Moriyama N, Fukasawa R, Tsujimoto G, Tanaka T, Yano J, et al. Quantification and distribution of alpha1-adrenoceptor subtype mrnas in human proximal urethra. Br J Pharmacol 1998;123: ) Yablonsky F, Riffaud JP, Lacolle JY, Dausse JP. Alpha 1- and alpha 2-adrenoceptors in the smooth muscle of male and female rabbit urethra. Eur J Pharmacol 1986; 121:1-8 9) Schafer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, et al. Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn 2002;21: ) Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract symptomatology. Neurourol Urodyn 2000;19: ) Gerstenberg TC, Lykkegaard Nielsen M, Lindenberg J. Spastic striated external sphincter syndrome imitating recurrent urinary tract infection in females. Effect of long-term alpha-adrenergic blockade with phenoxybenzamine. Eur Urol 1983;9: ) Kawabe K, Niijima T. Use of an alpha 1-blocker, YM-12617, in micturition difficulty. Urol Int 1987;42: ) Yoshida O, Takeuchi H, Hida S, Tomoyoshi T, Arai Y, Okada K, et al. [Clinical efficacy and safety of long-term administration of YM617 for urinary obstruction of the lower urinary tract]. Hinyokika Kiyo 1991;37: ) Reitz A, Haferkamp A, Kyburz T, Knapp PA, Wefer B, Schurch B. The effect of tamsulosin on the resting tone and the contractile behaviour of the female urethra: a functional urodynamic study in healthy women. Eur Urol 2004;46: ) Abrams P. Urodynamic effects of doxazosin in men with lower urinary tract symptoms and benign prostatic obstruction. Results from three double-blind placebo-controlled studies. Eur Urol 1997;32: ) Cain MP, Wu SD, Austin PF, Herndon CD, Rink RC. Vol. 12, No. 1,

8 이규성 한덕현 김지영 정진우 추설호 김준철 서주태 주명수 Alpha blocker therapy for children with dysfunctional voiding and urinary retention. J Urol 2003;170: ) Andersen M, Dahlstrand C, Hoye K. Double-blind trial of the efficacy and tolerability of doxazosin in the gastrointestinal therapeutic system, doxazosin standard, and placebo in patients with benign prostatic hyperplasia. Eur Urol 2000;38: ) Roehrborn CG, Prajsner A, Kirby R, Andersen M, Quinn S, Mallen S. A double-blind placebo-controlled study evaluating the onset of action of doxazosin gastrointestinal therapeutic system in the treatment of benign prostatic hyperplasia. Eur Urol 2005;48: ) Kumar A, Mandhani A, Gogoi S, Srivastava A. Management of functional bladder neck obstruction in women: use of alpha-blockers and pediatric resectoscope for bladder neck incision. J Urol 1999;162: 대한배뇨장애요실금학회지

페링야간뇨소책자-내지-16

페링야간뇨소책자-내지-16 야간뇨의진단과치료 - 실제적접근 - Reference 1. Choo MS, Ku JH, Park CH et al. Prevalence of Nocturia in a Korean Population Aged 40 to 89 Years. Neurourol Urodyn 2008; 27:60-64. 2. Weiss JP. Prevalence