The Clinical Effect of Bosingunyang-tang on Chronic Non-bacterial Prostatitis/Chronic Pelvic Pain Syndrome : Randomized Double-blind, Placebo-controlled Clinical Trial

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․교신저자:이병철 서울특별시 동대문구 회기동 1 경희의료원 부속한방병원 한방 6내과 TEL:02-958-9182 FAX:02-958-9158 E-mail:[email protected]

․이 연구는 이 논문은 2006년도 경희대학교 한의과대학 부속 한방병원 임상연구비에 의하여 작성되었음.

TheCl i ni c a lEf f e c to f Bos i ngunyang-t angonChroni cNo n- ba c t e ri a l Pro s t a t i t i s /Chro ni cPe l vi cPa i nSyndro me:Ra ndo mi z e dDo ubl e - bl i nd,

Pl a c e bo - c o nt ro l l e dCl i ni c a lTri a l

Moon-kooSong,Ji-suckKang,Cheol-hoKang,Young-minAhn,Se-youngAhn,Ho-kyungDoo,Byung-cheolLee Dept.ofInternalmedicine,CollegeofOrientalMedicine,KyungHeeUniversity

TheCl i ni calEf f ectof Bosi ngunyang- t angonChr oni cNon- bact er i alPr ost at i t i s/Chr oni c Pel vi cPai nSyndr ome:Randomi z edDoubl e- bl i nd,Pl acebo- cont r ol l edCl i ni calTr i al

Moon-kooSong,Ji-suckKang,Cheol-hoKang,Young-minAhn,Se-youngAhn,Ho-kyungDoo,Byung-cheolLee Dept.ofInternalmedicine,CollegeofOrientalMedicine,KyungHeeUniversity

ABSTRACT

Objective:Although chronicprostatitis/chronicpelvicpain syndrome(CP/CPPS) isa common disease,thereisno consensusontheetiologyorpathologyandtreatment.Thiswasadouble-blinded,placebo-controlled,randomizedclinicaltrial, investigatingthetherapeuticeffectsofthetraditionalKoreanmedicine,Bosingunyang-tang(BSGYT).

Method:ParticipantswhometUSNationalInstitutesofHealth(NIH)consensuscriteriaforCP/CPPSwereentered afterapplyinginclusion/exclusioncriteria.TheywererandomizedtotheBSGYT orplacebogroup,andtreatedthreetimesa day for6 weeks.NIH-ChronicProstatitisSymptom Index(NIH-CPSI) wasused toestimatetheclinicalsymptomsof CP/CPPS.ProstaglandinE2andβ-endorphininprostaticfluid,collectedby2-glasspre-massageandpost-massagetest,were analyzedasfactorsassociatedwithpainandinflammation.

Result:ThemeandecreaseinNIH-CPSItotalscoreoftheBSGYT groupwas11.0points,whichis5.7pointsmorethan theplacebogroup.(MannWhitneytestP=0.038)AlsotheBSGYT groupshowedthreetimeshigherresponseratethanthe placebogroupinNIH-CPSIpainsubscalescore.(Fisher'sexacttestP=0.027)Inthoseresponders,prostaglandinE2decreased significantly.(Wilcoxon'ssigned-rankstestP=0.037).Nospecificsideeffectswereobserved.

Conclusion:Aftera6-weektreatmentperiod,BSGYT improvedclinicalsymptomsofCP/CPPSpatientsbydecreasing PGE2levelinprostaticfluid.

Keywords:Bosingunyang-tang,chronicprostatitis,chronicpelvicpainsyndrome,prostaglandinE2,Bushenjianyang-tang

Ⅰ.I n t r oduc t i on

Chr oni cpr os t at i t i s /Chr oni cpe l vi cpai ns yndr ome

(CP/CPPS)i st het hi r dmos ti mpor t antpr os t at i c

di s e as eaf t e rBe ni gn Pr os t at i cHype r pl as i a(BPH)

and pr os t at ec anc e r

¹

.I ti sas s oc i at e d wi t h hi gh

mor bi di t y ; 8% of ambul at or y vi s i t s wi t h

ge ni t our i nar y s ympt oms ar e di agnos e d as

CP/CPPS,andi ti smor ec ommoni n36~65ye ar s

ol dme n

²

.ButCP/CPPSi sdi agnos e donl yont he

bas i sofs ympt oms ,pr i nc i pal l ypai nordi s c omf or t

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i n t hepe l vi cr e gi on,and no obj e c t i veme as ur e s c anhe l pde f i net hedi s e as e

³

.

Ur ol ogi c alpai nc ompl ai nt swe r er e c ogni z e dasa pr i mar y c ompone nt of CP/CPPS by NI H- c ons e ns us de f i ni t i on

⁴

.Thi s pai n i s a di s t i nc t i ve f e at ur e of CP/CPPS among t hr e e s ympt om c at e gor i e sofCP/CPPS(Pai n,Voi di ngc ompl ai nt s , s e xualdys f unc t i on),and t hee f f e c ton ape r s on' s l i f ewi t ht hatpai nhasbe e nl i ke ne dt ot hee f f e c t ofhavi ngmyoc ar di aci nf ar c t i on,angi naorCr ohn' s di s e as e

^5-⁷

.

I ns pi t eoft he s ehi ghmor bi di t yande f f e c ton Qual i t yofLi f e (QoL),t he r ei snoc ons e ns usoni t s e t i ol ogy,pat hol ogy and t he r e f or e t r e at me nt

⁸

.I n Kor e a, ur ol ogi s t s us e ant i bi ot i c s and al pha bl oc ke r sast he i rf i r s tc hoi c ewi t houtl oc al i z at i on e ve n t hough t he y do nott hi nk hi dde n bac t e r i al pr os t at i t i s i s t he e t i ol ogy ofCP/CPPS

⁹

.The s e di s c r e panc i e s ar e due t o unc l e ar e t i ol ogy and i ne f f e c t i ve ne s s of any e s t abl i s he d t r e at me nt s . Whe r e asTr adi t i onalKor e an Me di c i nei spopul ar f orc ondi t i onsnotmanage ds uf f i c i e nt l ybyWe s t e r n me di c i ne ,l i ke CP/CPPS.We r e por t a doubl e bl i nde d,r andomi z e dc ont r ol l e dt r i alf orCP/CPPS wi t hhe r balme di c i ne , Bos i ngunyang - t ang(BSGYT).

Ⅱ.Me t hods

1.Subj ect sofcl i ni calst udy

Thi ss t udywasc ar r i e doutbe t we e nOc t obe r18, 2007 and De c e mbe r 22,2007 i n t he Or i e nt al Me di c al Hos pi t al , Kyung He e Uni ve r s i t y.

Par t i c i pant s me t NI H CP/CPPS c ons e ns us c r i t e r i a.El i gi bi l i t yr e qui r e me nt si nc l ude dagef r om 18 t o 50 ye ar s - ol d, NI H Chr oni c Pr os t at i t i s Sympt om I nde x(NI H-CPSI ) t ot al s c or e hi ghe r t han15(s c al e0~43),I PSSt ot als c or ehi ghe rt han

8,ands ympt omsl as t i ngove r3mont hsdur i ngt he pr e vi ous6 mont hs .Af t e ra me di c alhi s t or y and phys i c ale xami nat i on,par t i c i pant s we r e e xc l ude d f r om t he s t udy, i f t he y had s ome ur ol ogi c al di s e as e (ac ut e pr os t at i t i s or bac t e r i alpr os t at i t i s , be ni gn pr os t at i c hype r t r ophy, pr os t at i c c anc e r , ur i nar y t ube r c ul os i s , ur i nar y t r ac t i nf e c t i on, bl adde r s t one , ur e t hr al s t r i c t ur e , i nt e r s t i t i al c ys t i t i s ,ur e t hr i t i s ,ne ur opat hi c bl adde r ,bl adde r c anc e r , he mat ur i a), dr ug hi s t or y(dr ug t he r apy wi t h ant i bi ot i c s , mus c l e r e l axant , nons t e r oi dal ant i - i nf l ammat or ydr ug,anal ge s i c swi t hi n1mont h orpr e s ume dt ohavei t ),di s e as e swhi c hi nf l ue nc e ur ol ogi c al s ympt oms (br ai n di s e as e , s e xual l y t r ans mi t t e ddi s e as e s ,e t c . )oranyac ut edi s e as eor di s e as et hats houl dbet r e at e d.

2.Cl i ni calSt udydesi gn

A 6-we e k doubl e - bl i nde d, pl ac e bo- c ont r ol l e d, r andomi z e d c l i ni c al t r i al was c onduc t e d.

Par t i c i pant swe r eas s i gne d t oBSGYT(N=14)or Pl ac e bo(N=13)gr oupe qual l y.The ywe r et r e at e d wi t h BSGYT (aque ouse xt r ac t s6g) orpl ac e bo me di c i ne(aque ouse xt r ac t s6g)t hr e et i me saday f or6we e kswi t houtwas hi ngoutpe r i od,be c aus e t he yhadnott ake nanydr ugsf orove ramont h.

Eve r y pat i e nt s we r e t aug ht wi t h a pape r about

l i f e s t yl ei nt e r ve nt i onsl i kehothi p bat h ore xe r c i s e ,

andt he ywe r ee nc our ag e dt oavo i dal c oholo rc af f e i ne .

Thepat i e nt swe r eas s e s s e datbas e l i neandaf t e r

3and 6we e ksby us i ngKor e an ve r s i on oft he

NI H- CPSIand I PSS

²⁷

.Bot h que s t i onnai r e swe r e

val i dat e d.Labor at or y and phys i c alas s e s s me nt s

we r e pe r f or me d atbas e l i ne and af t e r 6 we e ks .

Expr e s s e d pr os t at i cs e c r e t i on(EPS) s ampl e swe r e

c ol l e c t e dby2- gl as spr e -mas s ageandpos t - mas s age

t e s t .EPSs ampl e swe r epr e s e r ve dat- 80° C be f or e

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anal ys i s

²²

.ELI SA as s ayswe r eus e dt ome as ur eβ - e ndor phi n and pr os t agl andi n E2, f ac t or s as s oc i at e d wi t h pai n and i nf l ammat i on.

(pr os t agl andi n E2:Cayme n Che mi c alCo. ,Ann Ar bor , Mi c hi gan, β-e ndor phi n : Pe ni ns ul a Labor at or i e s , San Car l os , Cal i f or ni a. , USA) Rout i ne ur i ne anal ys i s and c ul t ur e s we r e pe r f or me d on al lur i nes ampl e s .Al lpar t i c i pant s s i gne d a c ons e nt f or m and The I ns t i t ut i onal Re vi e w Boar d oft he Kor e an Me di c alHos pi t al , KyungHe eUni ve r s i t yappr ove dt hi st r i al .

3.Pr epar at i onofBSGYTaqueousext r act s Bos i ngunyang- t ang (BSGYT) e xt r ac t powde r was obt ai ne d f r om t he De par t me nt of Phar mac e ut i c alPr e par at i on ofOr i e nt alMe di c i ne , Or i e nt alMe di c alHos pi t al ,KyungHe eUni ve r s i t y.

BSGYT e xt r ac tpowde ri sadr i e dmi xt ur eoft he f ol l owi ngr aw mat e r i al s:20gm ofRe hmanni ae Radi xPr e par atandPor i a,12gm ofLyc i iFr uc t us , 8gm ofDi os c or e aeRhi z oma and Cor niFr uc t us , 6gm ofEuc ommi ae Cor t e x,Mor i ndae of f i c i nal i s

Radi x, Cynomor i i He r ba and Ac hyr ant hi s Bi de nt at ae Radi x, 4gm of Ci t r i Pe r i c ar pi um, Ange l i c ae gi gant i sRadi x and Ps or al e ae Fr uc t us , 3gm of Pol ygal aeRadi x,Sc hi z andr aeFr uc t usand AmomiFr uc t us (Tabl e 1).Pl ac e bo mat e r i alwas made of c or n s t ar c h and l ac t os e . We us e d Phe nyl t hi oc ar bami de and Ci t r i c ac i d f or t as t e , s s anghwa f l avour f or s me l l ,c ar ame land s e pi a c ol ort o l ooksl i keBSGYT e xt r ac t .Thee xt r ac t powde rofBSGYT andPl ac e bowasmanuf ac t ur e d unde r t he Good Manuf ac t ur i ng Pr ac t i c e (GMP) s ys t e m,and t hequal i t i e soft he s er aw mat e r i al s we r et e s t e dac c or di ngt ot heKor e aFood& Dr ug Admi ni s t r at i on and hos pi t al s t andar ds . The ai r dr i e d and c r us he d mat e r i al s we r e adde d t o di s t i l l e d wat e r ,and e xt r ac t i on waspe r f or me d by he at i ngf or4h at100° C.The n t hee xt r ac twas c onc e nt r at e d wi t h a r ot ar y e vapor at or (Mode l NE- 1,EYELA Co. ,Japan) and dr i e d wi t h a Fr e e z eDr ye r(Mode lFD- 1,EYELA Co. ,Japan).

Thec ol l e c t i on r at eoft hef i nalaque ouse xt r ac t s was11. 8%.

He r balname He r bme di c i ne dos e (gm) 熟地黃 Re hmanni aeRadi xPr e par at 20. 0

茯神 Por i a 20. 0

枸杞子 Lyc i iFr uc t us 12. 0 山藥 Di os c or e aeRhi z oma 8. 0 山茱萸 Cor niFr uc t us 8. 0 杜冲鹽水炒 Euc ommi aeCor t e x 6. 0 巴戟天酒蒸 Mor i ndaeof f i c i nal i sRadi x 6. 0 鎖陽 Cynomor i iHe r ba 6. 0 牛膝 Ac hyr ant hi sBi de nt at aeRadi x 6. 0 陳皮 Ci t r iPe r i c ar pi um 4. 0 當歸 Ange l i c aegi gant i sRadi x 4. 0 補骨脂鹽水炒 Ps or al e aeFr uc t us 4. 0 遠志 Pol ygal aeRadi x 3. 0 五味子 Sc hi z andr aeFr uc t us 3. 0

砂仁 AmomiFr uc t us 3. 0

Tot alamount 113. 0

Tabl e1.Thecont ent sof Bosi ngunyang-t ang(BSGYT)

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4.Out comes

The NI H- Chr oni c Pr os t at i t i s Sympt om I nde x (NI H- CPSI ) was de ve l ope d f or us e i n c l i ni c al t r i al s . I t me as ur s e t he t hr e e mos t i mpor t ant domai ns i n CP/CPPS; pai n,voi di ng s ympt oms andqual i t yofl i f e .Thes e ns i t i vi t yands pe c i f i c i t y oft heCPSIhasbe e nc onf i r me di nanumbe rof r andomi s e dpl ac e bo- c ont r ol l e dt r i al s

²⁹

.

The pr i mar y e ndpoi nt was a de c r e as e i n NI H-CPSIt ot als c or ef r om bas e l i net o we e k 6.

The s e c ondar y out c ome s i nc l ude d de c r e as e i n NI H-CPSIs ubs c al es c or e ,r e s pons er at eofCPSI t ot al s c or e or s ubs c al e s c or e , I nt e r nat i onal Pr os t at e Sympt om I nde x, c yt oki ne s l i ke β - e ndor phi nandpr os t agl andi nE2i npr os t at i cf l ui d.

5.Test st odet ectsi deef f ect s

To de t e c ts i dee f f e c t ,e ve n t hough no s pe c i f i c s i dee f f e c ti sknown,weobs e r ve d par t i c i pant s ' uns pe c i f i c c ompl ai nt and any pr ogr e s s i on of CP/CPPS s ympt omsate ve r yvi s i t .Fur t he r mor e , atpr i orandaf t e rt r e at me nt ,bl oods ampl e swe r e c ol l e c t e d f or c ompl e t e bl ood c ount , di f f e r e nt i al c ount (CBC&DC) and bi oc he mi s t r y t e s t t o e val uat e any abnor mal i t i e s ofl i ve rand ki dne y f unc t i on,orot he runknowns i dee f f e c t s .

6.St at i st i calAnal yses

Be c aus enot r i ali spe r f or me dwi t hBSGYT,t hi s t r i ali sbas e d on a t r i alwi t h f i nas t e r i de ,whi c h t ar ge t sCP/CPPSl i keBSGYT.Ac c or di ngt ot hi s as s umpt i on,s e t t i ngs i gni f i c anc eat0. 05wi t h 80%

powe r ,e ac hgr oupne e dsatl e as t7par t i c i pant s

²⁸

. Weus e dMann- Whi t ne yt e s tt oc ompar eNI H- CPSI

t ot al s c or e s , Fi s he r ' s e xac t t e s t t o c ompar e r e s ponde r sofe ac hgr oup,Wi l c oxon' ss i gne d- r anks t e s t t o c ompar e c yt oki ne l e ve l .(t he Gr aphPad Pr i s m f or Wi ndows , Ve r s i on 5. 01 (Gr aphPad Sof t war e ,I nc . )

Ⅲ.Res ul t s

1.Par t i ci pant s

Be t we e n Oc t obe r18,2007 and De c e mbe r22, 2007,34pat i e nt swe r es c r e e ne dand27par t i c i pant s we r e e nr ol l e d. Par t i c i pant s we r e as s i gne d t o Pl ac e bo or BSGYT gr oup e qual l y, wi t h a c omput e r ge ne r at e d, r andom, doubl e bl i nde d de s i gn.Two oft he s e par t i c i pant swe r e dr oppe d be c aus e t he y have s t oppe d me di c at i on,one f or Be l l ' spal s y t heot he rf orf ood poi s oni ng.Thr e e mor e par t i c i pant swi t hdr e w t he i ragr e e me nt sf or pe r s onalr e as onsl i kemove (Fi g.1).Be t we e n t he t wo gr oups , bas e l i ne de mogr aphi c & c l i ni c al c har ac t e r i s t i c s s uc h as age ,BMI ,dur at i on of s ympt oms , t r e at me nt hi s t or y, CPSI -t ot al s c or e and s ubs c al e s c or e ,I PSS,c yt oki ne l e ve l s we r e s i mi l ar (Tabl e2).

2.Pr i mar yOut come

Af t e r6we e ks ,t heBSGYT gr oupi mpr ove d5. 7

poi nt smor et han t hepl ac e bo gr oup on ave r age .

Theme ande c r e as ei nNI H- CPSIt ot als c or ewas

1 1. 0amongBSGYTpar t i c i pant s ,c ompar e dwi t h5. 3

amongt hepl ac e bopar t i c i pant s .(Mann Whi t ne y

t e s tP=0. 038)(Fi g.1)Node mogr aphi corc l i ni c al

c har ac t e r i s t i cwasas s oc i at e dwi t ht her e s ul t s .

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Char ac t e r i s t i c (SD) Cas e (N=12) Cont r ol (n=10) P val ue

^†

Age , me anye ar s 41. 8(5. 2)

^‡

39. 6(8) 0. 46 Dur at i onofs ympt oms ,mont hs 49. 5(26. 8) 62. 8(68. 3) 0. 54 He i ght 171. 1(11. 6) 173. 2(4. 9) 0. 31 We i ght 68(11. 6) 68. 2(9. 6) 0. 97 BMI 23. 14(3. 1) 22. 67(2. 6) 0. 71

Tr e at me nthi s t or y

^§

1. 0

0Tr e at me nt 1 0

1ormor et r e at me nt 11 10 NI H-CPSIs c or e

^¶

Tot al 23. 5(3. 7) 24. 3(3. 8) 0. 67 Pai ns ubs c al e 9. 8(2. 9) 11. 2(2. 7) 0. 25 Ur i nar ys ubs c al e 5. 8(2. 2) 4. 8(1. 7) 0. 28 QoLs ubs c al e 8(2. 2) 8. 3(1. 4) 0. 71 I PSS

^¶

19. 4(7. 7) 14. 9(5. 5) 0. 13 Cyt oki ne s

^¶

Pr os t agl andi nE2 67. 12 30. 08 0. 06 β-endor phi n 0. 13 0. 17 0. 25

*ApplyPerProtocolanalysis.†Pvaluewerebasedtwo-tailed,andsignificancewassetatp<0.05.‡mean(standard deviation)§Fisher'sExactTestwasused.¶Mann-Whitneytestwasused.

Tabl e2.Basel i neDemogr aphi candCl i ni calChar act er i st i cs*

Fi g.1.Cl i ni calt r i alcompar i ng BSGYT and Pl acebo f orCP/CPPS.Oft he 27 par t i ci pant s,22(81%) compl et edt r eat mentsessi onsof6weeks.

Withdrawalwasfive,twoforstoppingmedicinebecauseofchancedisease,threeforpersonalreasonlikemove away.Noparticipantscomplainedsignificantandseveresideeffects,orshowedlababnormality.

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3.Secondar yOut comes

Of t he 12 BSGYT par t i c i pant s , 10(83. 3%) r e s ponde d (de f i ne d as > 25% i mpr ove me nt i n NI H-CPSI

¹⁰

),c ompar e d wi t h 4(66. 7%)pl ac e bo par t i c i pant s (r e l at i ve r i s k[ RR] 2. 08, Conf i de nc e i nt e r val [ CI ] 0. 9- 4. 6 Fi s he r ' se xac tt e s tP=0. 07), i nc l udi ng 4 BSGYT and 1 pl ac e bo gr oup par t i c i pant sr e por t i ngmor et han5 0 % i mpr ove me nt . (non- s i gni f i c ant ).I n NI H-CPSI pai n s c or e ,10 par t i c i pant s of BSGYT r e s ponde d (de f i ne d as de c l i neofonet hi r d)c ompar e dt o3par t i c i pant sof pl ac e bo gr oup(r e l at i ver i s k[ RR] 2. 78,Conf i de nc e i nt e r val [ CI ]1. 04- 7. 40Fi s he r ' se xac tt e s tP=0. 027 (Fi g.2).

Fi g.2.Af t er6 weeks,NI H-CPSIt ot alscor e of BSGYT gr oup i mpr oved mor e t han 5 poi nt scompar edwi t hpl acebogr oup.

Themean decreasein NIH-CPSItotalscore was11.0amongBSGYT participants(★ Mann WhitneytestP=0.038).

I nt heCP/CPPSpat i e nt s ,PGE2c onc e nt r at i ons i npr os t at i cf l ui dar ehi ghe rt hani nas ympt omat i c c ont r ol s , and hi gh PGE2 mi ght i nhi bi t β - e ndor phi n r e l e as e

¹¹

.I n t hi s s t udy,PGE2 was de c r e as eby20. 73pg/dli nBSGYT gr oup,3. 12pg/dl i npl ac e bogr oup.PGE2de c r e as ewass i gni f i c anti n t hepar t i c i pant swhos eCPSI -pai ns c or ei mpr ove d.

(de f i ne d as de c l i ne of one t hi r d, Wi l c oxon' s s i gne d-r ankst e s t P=0. 037,(Fi g. 3).Changeofβ

- e ndor phi nwasi ns i gni f i c ant .

Fi g.3.I n NI H-CPSIpai n scor e,al most t hr ee t i mes of BSGYT gr oup r esponded compar ed wi t h pl acebo gr oup. (Fi sher ' s ex actt estP=0. 027)

Fi g.4.I n NI H-CPSIpai n-scor e r esponder s,we can obser v e a meani ngf uldecr ease i n PGE2( ★ Wi l cox on' s si gned-r anks t est P=0. 037), whi ch i nduces pai n i n CP/CPPSpat i ent s.

4.Si deef f ect s

CP/CPPS i s a c hr oni c di s e as e ,and pr os t at e bl ood s uppl y i s poor . The r e f or me di c i ne s f or CP/CPPSmi ghtbeus e di nl ongt e r m ori nl ar ge dos age ,s ot he yar er e qui r e dt obet e s t e df ors i de e f f e c t s .The r ewasnos pe c i f i cc ompl ai nte xc e ptf or apl a c e bopar t i c i pant swhoc o mpl ai ne dmi l ddys pe ps i a.

No s i g ni f i c ant adve r s e c hang e i n bi oc he mi s t r y,

CBC&DC wasobs e r ve di nbot hg r oup.

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Ⅳ.Di s cus s i on

I t has be e n s ugge s t e d t hat many ur ol ogi c al c ondi t i ons s uc h as be ni gn pr os t at i c hype r pl as i a (BPH), c hr oni c pr os t at i t i s , voi di ng or e r e c t i l e dys f unc t i onmi ghtbeame nde dbyc ompl e me nt ar y and al t e r nat i ve me di c i ne t r e at me nt s t r at e gi e s . Bi of e e dbac k, ac upunc t ur e , hi gh f r e que nc y e l e c t r os t i mul at i on, hype r t he r mi a, and he r bal me di c i nehasbe e n us e d f orCP/CPPS butmor e e vi de nc e i sne e de d f orhe r balme di c i ne

^12,²⁵

.Thi s doubl e -bl i nde d pl ac e bo- c ont r ol l e d r andomi z e d c l i ni c al t r i al wi t h Bos i ngunyang-t ang(BSGYT) r e ve al e dmar ke di mpr ove me ntoft ot alNI H- CPSI s c or eand hi gh r e s pons er at ei n CPSI -pai n s c or e wi t hade c r e as ei nPGE2.

Pai n de c r e as e i s a c l i ni c al l y i mpor t ant i mpr ove me nt i n i ndi vi dual pat i e nt s e ve n i f i mpr ove me nt of ur i nar y s ympt oms i s not s uf f i c i e nt

¹³

.Pai n i snotonl y t houghtt o bet he pr i mar y s ympt om,butal s o a c e nt r alf e at ur ei n QoL

¹⁴

. Thi s c e nt r al and/or pe r i phe r al pai n s e ns i t i z at i on i n t he pe l vi s may r e s ul t f r om t e nde r ne s sofpr os t at eand pe l vi s ,s oac upunc t ur e wasr e gar de dasani mpor t antc ompl e me nt ar yand al t e r nat i vet he r apy t o t r e atpai nf uland c hr oni c c ondi t i ons

^15,¹⁶

.Buti ti sal s o i mpor t antt o not e t hathal foft heCP/CPPSpat i e nt ss uf f e r i ngf r om pai n hasnos i t e soft e nde r ne s swhat s oe ve r .Thi s he t e r oge ne i t y s howst he r ei sa ne e d f ora pai n c ont r ol t he r apy t hat i s not bas e d on mus c l e t e nde r ne s s .

Bos i ngunyang- t ang(BSGYT) c ons i s t soff i f t e e n me di c al he r bs , bas e d on Yukmi j i hang- t ang (YMJHT). YMJHT i s us e d f or t e at i ng Yi n de f i c i e nc y of l i ve r and ki dne y, he c t i c f e ve r , di z z i ne s s ,i nf l ammat i onandgyne c ol ogi c aldi s e as e s .

Al s o,i ti sac ar di act oni c& di ur e t i c ,and t he s e ac t i ons ar e pr obabl y e f f e c t e d by vas odi l at i on

¹⁷

. Bas e d on YMJHT, BSGYT was made f or

"de f i c i e nc y ofYangi n Yi n"be c aus et e ndon and mus c l e i s s t r e ngt he ne d by Yang i n Tr adi t i onal Kor e anMe di c alt he or y.Addi t i onalme di c i ne si sf or

"De f i c i e nc y of Yang. " The s e s me di c i ne s have ant i - i nf l ammat or y or ant i oxi dant e f f e c t s . For e xampl e , Ange l i c ae gi gant i s Radi x i nhi bi t i nf l ammat or y me di at or s and Lyc i i Fr uc t us , Mor i ndae of f i c i nal i s Radi x have ant i oxi dant e f f e c t

^18,¹⁹

.Asa r e s ul t ,BSGYT t r e at sCP/CPPS, whi c h r e f l e c t s"de f i c i e ntqi "(e ne r gy ofl i f e ) wi t h f oc al i nf l ammat i on and ur i nar y s ympt oms i n Tr adi t i onal Kor e an Me di c al t he or y, and i t i mpr ove d t het ot alNI H-CPSIs c or eand s howe d hi gh r e s pons er at eofCPSI - pai n s ubs c al es c or e

²⁰

. Thi si smor es i gni f i c antt han t r adi t i onalChi ne s e f or mul aer e por t e dbe f or e2003,andase f f e c t i veas Que r c e t i n

^21,²⁵

.(i mpr ove me ntf r om 21. 0t o13. 1,i n NI H- CPSIt ot als c or e )

BSGYT may have s ome e f f e c t s on i mmune r e ac t i on. I n me n wi t h CP/CPPS, t he ac t i on be t we e n t he i mmune , e ndoc r i ne and ne r vous s ys t e msi si nvol ve d i n pr oduc i ng s ympt omsl i ke pai n. I nf l ammat or y mar ke r pr os t agl andi n E2(PGE2)i ss ynt he s i z e d f r om t hee xpr e s s i on of Cyc l o- oxyge nas e -t ype -2(Cox- 2), and r e s ul t s i n pai n.

²²⁾

PGE2 i s al s o known t o i nhi bi t β - e ndor phi n,an e ndoge nous opi oi d pr oduc e d by i mmune c e l l s , and t r e at me nt s wi t h ant i bi ot i c s de c r e as ePGE2andi nc r e as eβ-e ndor phi nt he r e f or r e l i e ve pai n

^23,²⁶

.I n t hi st r i al ,BSGYT de c r e as e d PGE2 l e ve l , e s pe c i al l y i n par t i c i pant s whos e CPSI -pai ns ubs c al es c or ede c r e as e d.

Thi ss t udy hass omel i mi t at i ons .I n t hi st r i al ,

NI H- CPSI t ot al s c or e was t he mos t val i d

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me as ur e , but t he s c or e i s s ubj e c t i ve t o t he par t i c i pant ' s pe r s onal at t e nt i on i n bot h gr oup.

Al s o,t henumbe rofpar t i c i pantwass mal l (N=22), andt hedur at i onoft het r i alwass hor t (6we e ks ).

Se l e c t i ngBSGYT mi ghtbes e e me di nade quat eby s ome Tr adi t i onalKor e anMe di c aldoc t or s .

Ⅴ.Conc l us i on

I n s ummar y,t heBSGYT gr oup i mpr ove d 11 poi nt s , 5. 7 poi nt s mor e on ave r age t han t he pl ac e bo gr oup.And t he BSGYT gr oup s howe d t hr e et i me shi ghe rr e s pons er at et hant hepl ac e bo gr oup.The s e e f f e c t s mi ght have r e s ul t e d f r om PGE2 de c r e as e i n pr os t at i c f l ui d.Cl i ni c alt r i al s wi t h l onge r t r e at me nt pe r i od ar e i ndi c at e d t o r e ve al mor e e f f e c t s on e ndoc r i ne and ne r vous s ys t e m.

Ref e r en ce

1. Robe r t s RO, Li e be r MM, Bos t wi c k DG, Jac obs e n SJ. A r e vi e w of c l i ni c al and pat hol ogi c al pr os t at i t i s s yndr ome s . Ur ol ogy.

1997;49(6):809-21.

2.Sc hae f f e r AJ.Et i ol ogy and manage me nt of c hr oni cpe l vi cpai ns yndr omei nme n.Ur ol ogy.

2004;63(3Suppl1):75- 84.

3. Al e xande r RB, Pr ope r t KJ, Sc hae f f e r AJ, Landi s JR,Ni c ke lJC,O' Le ar y MP e t al . Ci pr of l oxac i n or t ams ul os i n i n me n wi t h c hr oni cpr os t at i t i s /c hr oni cpe l vi cpai ns yndr ome : a r andomi z e d,doubl e - bl i nd t r i al .Ann I nt e r n Me d.2004;141(8):581-9.

4. Kr i e ge r JN, Nybe r g L, Ni c ke l JC. NI H c ons e ns us de f i ni t i on and c l as s i f i c at i on of

pr os t at i t i s .JAMA.1999;282(3):236- 7.

5.Col l i nsMM,St af f or dRS,O' Le ar yMP,Bar r y MJ. Di s t i ngui s hi ng c hr oni c pr os t at i t i s and be ni gnpr os t at i chype r pl as i as ympt oms :r e s ul t s of a nat i onal s ur ve y of phys i c i an vi s i t s . Ur ol ogy.1999;53(5):921-5.

6.Kr i e ge r JN,Egan KJ,Ros s SO,Jac obs R, Be r ge rRE.Chr oni cpe l vi cpai nsr e pr e s e ntt he mos t pr omi ne nt ur oge ni t al s ympt oms of

"c hr oni cpr os t at i t i s ".Ur ol og y.1 996 ;48 (5 ): 715 - 21;

di s c us s i on721-2.

7.We nni nge rK,He i manJR,Rot hmanI ,Be r ghui s JP,Be r ge r RE.Si c kne s s i mpac t of c hr oni c nonbac t e r i al pr os t at i t i s and i t s c or r e l at e s .J Ur ol .1996;155(3):965- 8.

8 .Sc hae f f e rAJ.Cl i ni c alpr ac t i c e .Chr oni cpr os t at i t i s andt hec hr oni cpe l vi cpai ns yndr ome .N EnglJ Me d.2006;355(16):1690- 8.

9.KuJH,Pai c kJS,Ki m SW.Chr oni cpr os t at i t i s i n Kor e a: a nat i onwi de pos t al s ur ve y of pr ac t i c i ng ur ol ogi s t si n 2004.As i an J Andr ol . 2005;7(4):427- 32.

1 0 .Me hi kA,Al asP,Ni c ke lJC,Sar pol aA,He l s t r öm PJ.Al f uzos i nt r eat me ntf orc hr oni cpr os t at i t i s / chr oni c pel vi c pai n s yndr ome : a pr os pe ct i ve , r andomi z ed, doubl e-bl i nd, pl ac ebo-cont r ol l ed, pi l ots t udy.Ur ol ogy.2003;62(3):425-9.

11.Pont ar iMA,Ruggi e r iMR.Mec hani s ms i n pr os t at i t i s /chr oni c pel vi c pai n s yndr ome . J Ur ol .2008;179(5Suppl ):S61-7.

12.Capodi ceJL,Be mi sDL,But t yan R,Kapl an SA,Kat zAE.Compl e ment ar yandal t er nat i ve me di c i nef orchr oni cpr os t at i t i s /chr oni cpe l vi c pai n s yndr ome. Evi d Bas e d Compl eme nt Al t er natMed.2005;2(4):495-501.

13.Pr oper t KJ,Li t wi n MS,Wang Y,et al .

Res pons i venes soft heNat i onalI ns t i t ut esof

(9)

He al t h Chr oni c Pr os t at i t i s Sympt om I nde x (NI H- CPSI ). Qual Li f e Re s . 2006;15(2) :299- 305.

14.Ni c ke lJC,Tr i pp DA,ChuaiS,Li t wi n MS, Landi sJR,Al e xande rR,e tal .Ps yc hos oc i al var i abl e s af f e c t t he qual i t y ofl i f e ofme n di agnos e dwi t hc hr oni cpr os t at i t i s /c hr oni cpe l vi c pai ns yndr ome .BJU I nt .2008;101(1):59- 64.

15.Be r ge rRE,Ci olMA,Rot hmanI ,Tur ne rJA.

Pe l vi ct e nde r ne s si snotl i mi t e dt ot hepr os t at e i n c hr oni c pr os t at i t i s /c hr oni c pe l vi c pai n s yndr ome (CPPS) t ype I I I A and I I I B:

c ompar i s on of me n wi t h and wi t hout CP/CPPS.BMC Ur ol .2007;7:17.

16.Capodi c eJL,Ji n Z,Be mi sDL,SamadiD, St oneBA,KapanS,e tal .A pi l ots t udyon ac upunc t ur ef orl owe rur i nar yt r ac ts ympt oms r e l at e d t o c hr oni c pr os t at i t i s /c hr oni c pe l vi c pai n.Chi nMe d.2007;2:1.

17.Ji nUH,Ki m DI ,Le eTK,Le eDN,Ki m JK, Le e I S e t al .He r balf or mul at i on,Yukmi - j i hang-t ang- Jahage ,r e gul at e s bone r e s or pt i on by i nhi bi t i on ofphos phor yl at i on me di at e d by t yr os i ne ki nas e Sr c and c yc l ooxyge nas e e xpr e s s i o n.JEt hno phar mac ol .2 0 0 6 ; 1 0 6 (3 ) : 3 3 3 - 4 3 . 18.Ki m JH,Je ongJH,Je onST,Ki m H,Oc kJY, SukKH e tal .De c ur s i ni nhi bi t si nduc t i onof i nf l ammat or y me di at or s by bl oc ki ng nuc l e ar f ac t or - kappaB ac t i vat i oni nmac r ophage s .Mol Phar mac ol .2006;69(6):1783- 90.

19.Li nRD,HouWC,Ye nKY,Le eMH.I nhi bi t i on ofmonoami neoxi das eB (MAO- B)byChi ne s e he r balme di c i ne s .Phyt o me di c i ne .2 0 0 3 ; 1 0 ( 8 ) : 6 5 0 - 6 . 20.Le eSWH,Li ongML,Yue n KH,Le ongWS, Che e PY,Choong WP e t al .Ac upunc t ur e ve r s uss ham ac upunc t ur ef orc hr oni cpr os t at i t i s /c hr oni cpe l vi cpai n.Am JMe d.2008;121(1)

:79. e 1- 7.

21.Shos ke sDA,Ze i t l i n SI ,Shahe d A,Raj f e rJ.

Que r c e t i n i n me n wi t h c at e gor y I I I c hr oni c pr os t at i t i s :apr e l i mi nar ypr os pe c t i ve ,doubl e - bl i nd,pl ac e bo- c ont r ol l e d t r i al .Ur ol ogy.1999;

54(6):960-3.

22.JangTL,Sc hae f f e rAJ.Ther ol eofc yt oki ne s i npr os t at i t i s .Wor l dJUr ol .2003;21(2):95- 9.

23. Vl as kovs ka M, He r t t i ng G, Kne pe l W.

Adr e noc or t i c ot r opi nandbe t a- e ndor phi nr e l e as e f r om r atade nohypophys i si nvi t r o:i nhi bi t i on bypr os t agl andi nE2f or me dl oc al l yi nr e s pons e t o vas opr e s s i n and c or t i c ot r opi n- r e l e as i ng f ac t or .Endoc r i nol ogy.1984;115(3):895-903.

24.Ni c ke lJC,Shos ke sD,WangY,e tal .How doe s t he pr e - mas s age and pos t - mas s age 2- gl as s t e s tc ompar e t o t he Me ar e s -St ame y 4- gl as st e s ti n me n wi t h c hr oni c pr os t at i t i s /c hr oni cpe l vi cpai n s yndr ome ?J.Ur ol .2006

;176(1):119-24.

25.Che nJX,HuLS.Tr adi t i onalc hi ne s eme di c i ne f or t he t r e at me nt of c hr oni c pr os t at i t i s i n Chi na:as ys t e mat i cr e vi e w andme t a-anal ys i s . Jour nal of Al t e r nat i ve and Compl e me nt ar y Me di c i ne(Ne w Yor k,N. Y. ).2006;12(8):763- 9.

26.Ni c ke lJC.I nf l ammat i onandbe ni gnpr os t at i c hype r pl as i a.Ur ol .Cl i n.Nor t hAm.2008;35(1) :109- 15;vi i .

27.Chong CH,Ryu DS,Oh TH: TheKor e an ve r s i on ofNI H-Chr oni cPr os t at i t i sSympt om I nde x (NI H- CPSI ): val i dat i on s t udy and c har ac t e r i s t i c sonc hr oni cpr os t at i t i s .Kor e anJ Ur ol .2001;42:511-20.

28.Ni c ke lJC,Downe yJ,Pont ar iMA,Shos ke sDA,

Ze i t l i n SI . A r andomi z e d pl ac e bo- c ont r ol l e d

mul t i c e nt r es t udy t o e val uat et hes af e t y and

e f f i c ac y off i nas t e r i def ormal ec hr oni cpe l vi c

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