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1 염증성만성골반통증후군환자에서항생제단독요법과항생제및알파차단제병합요법의치료효과비교 Comparison of the Efficacy of Antibiotic Monotherapy and Antibiotic Plus Alpha-blocker Combination Therapy for Patients with Inflammatory Chronic Prostatitis/Chronic Pelvic Pain Syndrome Chul Woong Youn, Kyung-Chul Son, Hyang-Sik Choi, Dong Deuk Kwon, Kwangsung Park, Soo Bang Ryu From the Department of Urology, Chonnam National University Medical School, Gwangju, Korea Purpose: The objectives of this study was to compare the efficacy of antibiotic monotherapy with antibiotic plus alpha-blocker combination therapy for the treatment of inflammatory chronic pelvic pain syndrome (CPPS) patients. Materials and Methods: Between October 2005 and May 2006, 69 patients who were diagnosed as CPPS (National Institutes of Health; NIH-catagory IIIa), were included in this study. The patients were randomly placed into two groups: group I was treated with gatifloxacin alone (35 patients), and group II was treated with gatifloxacin and doxazosin (34 patients) for 6 weeks. For all the patients, the urinalysis, expressed prostatic massage, the National Institute of Health-Chronic Prostatitis Symptom Index (NIH- CPSI) and a distal rectal examination (DRE) were performed at the initial visit. The NIH-CPSI was compared both before and after the treatment. Results: On the initial diagnosis, the mean CPSI of the group I patients was 24.0±6.3, and that for the group II patients was 24.7±6.9. After the treatment, that of the group I was 16.6±5.4, and that of group II was 13.4±5.3. After 6 weeks of treatment, the changes in the total CPSI scores had significantly improved in group II compared with group I (p<0.05). A statistically significant improvement occurred in the pain score, the voiding symptom score and the quality of life in the group II compared with group I (p<0.05) Conclusions: This study suggests that combination therapy of antibiotic plus alpha-blocker would be more effective than antibiotic monotheraphy for treating patients with inflammatory chronic prostatitis/chronic pelvic pain syndrome. (Korean J Urol 2008;49:72-76) Key Words: Prostatitis, Pelvic pain, Adrenergic alpha-blockers, Antibiotics 대한비뇨기과학회지제 49 권제 1 호 2008 전남대학교의과대학비뇨기과학교실 윤철웅ㆍ손경철ㆍ최향식권동득ㆍ박광성ㆍ류수방 접수일자 :2007년 7월 25일채택일자 :2007년 11월 5일 교신저자 : 류수방전남대학교병원비뇨기과광주시동구학동 8 번지 TEL: FAX: sbryu@chonnam. ac.kr 서론만성전립선염은단순한단일질환이라기보다는다양한원인에의해다양한병태를나타내는복합성질환이다. 생활전반부에걸쳐불편을초래하여삶의질에심각한영향을끼치고, 성인남성의 50% 가평생에한번은통증과배뇨 증상을경험하게되고 50대이하의가장흔한비뇨기과질환으로외래환자의 25% 가만성전립선염환자군으로추정될정도로흔한질환이다. 1,2 전립선염을최근에는 NIH분류에따라크게 4가지로분류하고있으며이중 category III는증상있는전립선염환자의 90% 이상이이에해당되며, 급성요도염, 비뇨기계암, 요도협착, 신경인성방광등의비뇨기계질환없이전립선통이나골반통이있는경우를만성 72

2 윤철웅외 : 염증성만성골반통증후군환자의항생제단독요법과알파차단제병합요법의치료효과비교 73 전립선염 / 만성골반통증후군으로정의하였고전립선마사지액이나마사지후소변또는정액에서염증소견을보이는경우를 IIIa 염증성으로, 염증소견이없는경우를 IIIb 비염증성으로세분하였다. 3 만성골반통증후군의원인은요도내요의전립선관으로의유입, 골반근육의긴장성통증, 감정적혹은정신적인이상, 감염등으로설명되고있으나아직분명치않다. 4 가장가능성높은원인으로요도내압의증가와방광경부및전립선평활근의수축으로전립선내로요가역류하여, 이로인한염증과통증이수반된다는가설이제시되고있으며, 이러한병인이염증성만성골반통증후군에서항생제와알파차단제병합요법의근거를제공하고있다. 5-7 현재염증성만성골반통증후군환자의치료에사용되는약제는항생제, 알파차단제, 근이완제등이있으며최근이들약제에대한병합요법에대한연구가이루어지고있으나효과에있어서는다양한결과를보인다 이에저자는염증성만성골반통증후군에있어항생제와알파차단제를이용한단일요법과병합요법의효과를비교해보고자하였다. 대상및방법 2005년 10월부터 2006년 5월까지 8개월동안본원비뇨기과를방문한환자중전립선염증상을호소한환자 247명중이전치료경력이없으며염증성만성골반통증후군으로진단받은환자 69명을대상으로하였다. 하부요로증상을호소하는모든환자를대상으로병력청취, 신체검사, 직장수지검사, 소변검사, 소변배양검사, 전립선분비액검사, 배양검사및한글판만성전립선염증상점수를측정하였다. 이전에만성골반통증후군으로진단받고치료받은병력이있었던환자, 전립선비대증으로치료를받았던환자, 직장수지검사에서전립선용적이 30g 이상인환 자, 소변배양검사와전립선액배양검사에서양성소견을보인환자는본연구에서제외하였다. 병력, 신체검사그리고검사실검사에서만성골반통증후군으로진단할수있으면서전립선액의도말검사에서백혈구가 400배의고배율시야에서 10개이상관찰되고만성전립선염증상점수총점이 15점이상으로염증성만성골반통증후군으로진단된환자를대상으로하였다. 대상환자를무작위적으로 gatifloxacin (Gatiflo R ) 만투여한 35명 (I군) 과 gatifloxacin (Gatiflo R ) 과 doxazosin (Cardura XL R ) 을동시에투여한환자 34명 (II군) 으로나누었다. 약물치료는 I군에서는매일 gatifloxacin (Gatiflo R ) 200mg을 2회분복하였고, II군에서는매일 gatifloxacin (Gatiflo R ) 200 mg 2회분복과 doxazosin (Cardura XL R ) 을취침전 1회투여하였다. 6주간의치료후두군모두만성전립선염증상점수를자기기입식으로작성하게하여만성전립선염증상점수의변화를비교하였다. 만성전립선염증상점수표는환자의증상을통증또는불편감, 배뇨증상및삶의질에미치는영향의 3가지영역으로이루어진 National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) 11 를번역한한글판만성전립선염증상점수표를사용하였다. 또한치료후전립선액도말검사를실시하여백혈구수치변화를확인하였다. 전립선액도말검사의결과는 grade 0-5단계로나누어고배율시야당백혈구수가 5개미만이면 grade 0, 5-9개관찰되는경우 grade 1, 10-29개관찰되는경우 grade 2, 30-49개관찰되는경우 grade 3, 50-99개관찰되는경우 grade 4, 100 개이상관찰되는경우를 grade 5로정의하였다. 통계분석은 Student's t-test (paired) 를시행하여 p값이 0.05 미만일때통계학적으로유의한것으로판단하였다. 결과 I군과 II군의나이는각각 41.8±9.2세와 41.3±9.5세였으며, Table 1. Patients' characteristics Group I (n=35) Group II (n=34) p-value Age (mean, range) 41.8 (23-60) 41.3 (21-57) Duration of symptoms (mean, range) 21.8 (7-42) 23.3 (8-48) Baseline NIH-CPSI* Total (median, range) 24.0±6.3 (25, 15-38) 24.7±6.9 (26, 15-41) Pain domain 11.1±4.1 (11, 3-19) 11.4±4.2 (11.5, 2-20) Voiding domain 4.6±1.8 (5, 0-8) 4.9±2.1 (5, 1-9) Quality of life domain 8.1±1.9 (8, 5-12) 8.4±2.1 (9, 4-12) *NIH-CPSI: National Institute of Health-Chronic Prostatitis Symptom Index, Mean±SD, Group I: antibiotic alone, Group II: antibiotic plus alpha-blocker

3 74 대한비뇨기과학회지 : 제 49 권제 1 호 2008 증상기간은각각 21.8±10.4개월과 23.3±9.7개월이었다. 치료전만성전립선염증상점수는 I군에서 24.0±6.3점, II군에서 24.7±6.9점으로차이가없었다 (Table 1). 6주간의치료후만성전립선염증상점수는 I군 7.5점, II군 11.3점이었고, 감소치는 I군에서 16.5±5.4점, II군에서 13.4± 5.3점으로두군모두에서감소하였으나, II군에서더현저히감소하였다 (p<0.05). 만성전립선염증상의각항목을비교하면, 통증과관련된문항은 I군이 11.4±4.1에서 8.7±3.7 로평균 2.4점감소하였고, II군은 11.4±4.2에서 6.9±3.5로평균 4.5점감소하여 II군에서더감소하였다 (p<0.05). 배뇨증상과관련된문항은 I군이 4.6±1.8에서 4.9±2.1로평균 1.4 점감소하였고, II군은 4.9±2.1에서 2.6±1.4로평균 2.4점감소하여 II군에서배뇨증상이유의하게호전되었다 (p<0.05). 삶의질문항에서 I군이 8.1±1.9에서 4.6±1.6으로평균 3.5점감소하였고, II군은 8.4±2.1에서 3.9±1.8로평균 4.4점감소하여 II군에서유의하게증상이호전되었다 (p=0.046) (Table 2). 두군의치료전과후의만성전립선염증상점수는모든면에서 I군에비해항생제와알파차단제를함께사용한 II 군에서통계학적으로유의하게감소하였다. 전립선액도말검사의백혈구수치변화는 I군은치료전평균전립선액도말검사 grade는 3.27±1.14에서 1.61±1.24로감소하였고 (p<0.001), II군에서도치료전 3.38±1.25에서 1.52±1.35로감소하였다 (p<0.001) (Table 3). 고찰만성골반통증후군의원인으로는미생물, 바이러스, 자가면역병, cytokine, 전립선내로의요역류등이원인으로생각되고있으나아직명확하게밝혀진바는없다. 4 해부학적으로는알파교감신경하의요도내압 (urethral wall tension) 의증가, 12 특히방광경부보다는근위요도부위의증가가알려져있고요역동학적연구에서특징적으로최대요속이감소되어있고, 배뇨시에방광내압이낮은소견을보이며외요도괄약근의근전도가증가되는배뇨근-괄약근협조장애가나타난다. 이러한전립선요도부위와방광경부의기능이상이요도내압의증가를일으키고요도내압의증가가소변의전립선내로의역류를일으켜화학적전립선염을유발시키는것으로알려져있으며, 이러한이론적배경으로알파차단제가사용되고있다. 2,6,13 또한만성골반통증후군에알파차단제를사용하는몇가지이유를보면만성골반통증후군환자중일부에서배뇨장애증상을수반하고전립선비대증을동반하는경우가있고, 만성골반통증과하부요로증상을가진환자에서알파차단제가효과적이며, 비뇨기과의사에게친숙한알파차단제의경험적사용으로임상적으로환자들의증상호전을확인하고있기때문으로생각된다. 14 만성골반통증후군환자에서알파차단제의효과에대한연구들을보면, Barbalias 등 15 은비세균성전립선염환자 Table 2. Results of the NIH-CPSI* for the two groups Group I (n=35) Group II (n=34) NIH-CPSI NIH-CPSI p-value p-value Before Tx After Tx Before Tx After Tx Total (median, range) 24.0±6.3 (25, 15-38) 16.5±5.4 (17, 8-28) ±6.9 (26, 15-41) 13.4±5.3 (13.5, 4-25) Pain domain 11.1±4.1 (11, 3-19) 8.7±3.7 (8, 2-16) ±4.2 (11.5, 2-20) 6.9±3.5 (7.5, 0-13) Voiding domain 4.6±1.8 (5, 0-8) 3.2±1.6 (3, 0-6) ±2.1 (5, 1-9) 2.6±1.4 (3, 0-5) Quality of life domain 8.1±1.9 (8, 5-12) 4.6±1.6 (5, 2-8) ±2.1 (9, 4-12) 3.9±1.8 (4, 1-8) *NIH-CPSI: National Institute of Health-Chronic Prostatitis Symptom Index, Tx: treatment, Mean±SD, Group I: antibiotic alone, Group II: antibiotic plus alpha-blocker Table 3. Results of the EPS* for the two groups Group I (n=35) Group II (n=34) Before Tx After Tx p-value Before Tx After Tx p-value Grade (EPS) 3.27± ± ± ± *EPS grade 0: <5 white blood cells/high-power field (WBC/HPF), grade 1: 5-9 WBC/HPF, grade 2: WBC/HPF, grade 3: WBC/HPF, grade 4: WBC/HPF, grade 5: 100 WBC/HPF, EPS: expressed prostate secretion, Tx: treatment

4 윤철웅외 : 염증성만성골반통증후군환자의항생제단독요법과알파차단제병합요법의치료효과비교 명 (caterogy IIIa), 전립선통환자 72명 (caterogy IIIb), 그리고만성세균성전립선염환자 64명 (caterogy II) 을대상으로항생제와알파차단제를단독또는병합투여하여평균 22개월추적관찰한결과, 알파차단제가전립선통환자뿐만아니라비세균성전립선염과세균성전립선염에서도효과가있었고또한재발을줄이는효과가있다고보고하였다. Mehik 등 16 의연구에서도 alfuzosin을만성골반통증후군환자에서단독으로 6개월이상사용하였을때증상의호전이명확하게확인되며, alfuzosin의투여를중단하게되면다시증상이악화된다고하였고, Cheah 등 17 은 100명의새롭게진단된만성골반통증후군환자를대상으로 terazosin을 14주투여하였을때증상의호전을가져왔다고하여알파차단제가만성골반통증후군에서효과적임을보고하였다. 국내에서는 Jung 등 18 이 127명의환자를대상으로항생제, 소염제에 terazosin을병합투여하여치료효과를비교하였을때비염증성만성골반통증후군환자에서요속개선과통증, 불편감의유의한증상개선이있다고보고하였고, Ryu 등 19 은 40세미만의만성골반통증후군환자 57명을대상으로항생제와 alfuzosin의병합요법으로통증영역을제외한증상호전을보고하였다. 알파차단제사용에있어효과적인투여기간에대해서는아직정립되어있지않다. Lee 등 14 은최근연구에서 4-6주간의단기간투여보다는 12주이상의장기간투여시증상개선에보다효과적이라고하였으나, Nickel 등 20 은 58명의대상환자를 6주간 tamsulosin을투여하였을때증상개선이뚜렷하였으며, Neal과 Moon 21 도 25명의환자에서 4주간의 terazosin을투여하여 76% 에서증상개선이있었다고보고하여 4-6주간의단기간투여도증상개선에효과적임을주장하였다. 본연구에서도만성골반통증후군환자에서 6주간의항생제와알파차단제의병합요법이만성골반통증후군환자의증상개선에효과적임을확인하였다. Alexander 등 22 은이전치료에반응하지않은환자를대상으로항생제와알파차단제의병합요법을 6주간시행해보았을때, 유의한증상의호전을볼수없었다고하였으나, Mo 등 23 은이전치료경력이없는환자를대상으로 8주간항생제및알파차단제를사용하였을때증상개선에효과적이라고보고하였다. 본연구에서도이전치료경력이없는환자에서 6주간의항생제및알파차단제의투여가효과적이었다. 1981년 Osborn 등 24 이비선택적알파차단제인 phenoxybenzamine을 4주간사용하여 48% 의환자에서증상호전을보고한이래로여러종류의알파차단제의효과에대하여보고되고있다. Doxazosin에대해서는현재까지한편으로 Evliyaoglu와 Burgut 25 이 60명의환자를대상으로 12주간 doxazosin 단일제제를사용하여배뇨증상, 통증, 삶의질영역에서의의있게호전됨을보고하였다. Lee 등 14 은일반적으로선택적알파차단제보다는비선택적알파차단제가보다효과적이라고하였다. 항생제의경우일반적으로전립선염에서는증상치료율이약 40% 정도로알려져있으나 10,14 아직염증성만성골반통증후군에대해서는항생제투여군과위약군간의치료비교연구는없다. 하지만 Nickel 등 26 은임상적으로만성골반통증후군으로진단된환자에서 12주간 ofloxacin을사용하였을때약 50% 의증상호전을보인다하였고, 다른연구에서는 8 만성전립선염의 category와는무관하게항생제를사용하였을때각군간에유의한차이는없었지만증상의호전이있었다고보고하였다. 항생제로는 quinolone 제제가선호되는데전립선내로의투과율이뛰어나며광범위하게요로감염균주를제거하기때문이다. 27 본연구에서도염증성만성골반통증후군환자를대상으로항생제의단독사용군에서유의하게증상의호전을확인할수있었다. 본연구의대상환자의평균나이가약 42세고 60세미만의환자를대상으로비록직장수지검사를시행하였으나전립선초음파검사와요속검사가시행되지않아전립선비대증이동반된환자가포함되었을가능성을배제할수없다. 또한만성전립선염증상점수중배뇨증상에대한문항은잔뇨감, 빈뇨에대한두문항만으로구성되어배뇨에대한구체적인증상을대변하는데부족한점이있다. 하지만, 항생제와알파차단제의병합요법이통증및배뇨에관련된증상들과삶의질영역모두에서항생제단독요법보다병합요법시통계학적으로유의하게더효과적임을확인하였다. 결론염증성만성골반통증후군환자에서항생제단독요법과항생제와알파차단제의병합요법모두증상의호전을가져왔으나병합요법이통증증상, 배뇨증상및삶의질개선에서좀더나은효과를보였다. 또한 6주간의단기간요법이염증성만성골반통증후군환자에서효과적이었다. 항생제와알파차단제병합요법이염증성만성골반통증후군의치료에유의한효과를보였다. 향후알파차단제와항생제의투여기관과치료대상에대해서추가적인연구가필요할것으로생각한다. REFERENCES 1. Roberts RO, Lieber MM, Rhodes T, Girman CJ, Bostwick

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( )Kju269.hwp 만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University