1) 대한한방부인과학회지 THE JOURNAL OF ORIENTAL OBSTETRICS & GYNECOLOGY VOL.22 NO.4 : 083-093 (2009) 대구한의대학교한의과대학부인과교실 권지명, 박영선, 김동철 ABSTRACT Systemic Review on Complementary and Alternative Medicine for Endometriosis Ji-Myung Kwon, Young-Sun Park, Dong-Chul Kim Department of Oriental Obstetric & Gynecology, college of Oriental Medicine, DaeguHaany University Purpose: The aim of this study was to review systemically journals on the studies for complementary and alternative medicine in the treatment of endometriosis. Methods: Through medical websites, foreign clinical literatures about complementary and alternative medicines of endometriosis were searched. The cite used was http://www.pubmed.gov. And then they were divided into three groups. In vitro, in vivo, clinical studies. Results: 1. We researched 2 papers about in vitro. Both were used extract of herbal mixture. And they used CCL5, SE-1, COUP-TF, 17-β-HSD1, 17-β-HSD2 which were not commonly used in Korea. 2. We researched 8 papers about in vivo. Most of them used blood-activating stasis-dispelling medicine, just few used tonic medicine. And they used acupuncture which were not used in Korea. Most of Korean paper also used blood-activating stasis-dispelling medicine and rarely used tonic medicine. 3. We researched 19 papers about clinical studies. They had much more cases(average=60) than Korean paper. They were also used western medicine randomized sham-controlled trial. Conclusion: Afterward we need to study for comparing western medicine and herb medicine. And we concern about acupucture therapy. Key words: Endometriosis, Complementary and alternative medicine, Herb medicine, Acupuncture 교신저자( 김동철) : 경북포항시남구대잠동 907-8번지대구한의대부속포항한방병원 전화 : 054-271-8002 이메일 : kdc072@dhu.ac.kr 83
Ⅰ. 緖論 자궁내막증은자궁내막샘 (endometrial gland) 과기질(stroma) 을포함한자궁내 막조직이자궁내막강 (endometrial cavity) 이외의부위에부착하는것으로월경통, 성교통, 부정기출혈등의증상을야기 시키고불임의원인이되기도한다. 가 임기여성인구의 6-20% 에서발견되고, 자궁내막증을갖고있는여성의불임은 10-30% 까지다양하게보고되고있으며 최근에는그빈도가증가하는양상을보 이고있다. 아직까지확실한원인, 병태 생리, 치료방법이밝혀져있지않고보 존적치료후에도재발이흔한질환이 다. 자궁내막증의서양의학적치료는복 강경, 개복술을통한외과적치료, 혈중 에스트로겐을억제하는내과적약물치 료, 불임을위한치료, 그리고기대요법 및병합요법등이있다 1). 그러나수술은 재발이잦고약물치료는체중증가, 유방 축소, 다모증, 위축성질염, 질출혈, 질건 조증, 안면홍조, 여드름, 골다공증, 우울 증, 피로등의부작용등을나타내며 2,3) 약물치료로무월경상태가되면환자는 불임에대한두려움을가질수있다 4). 대체의학(alternative medicine) 이란정 통의학을대신한다는의미로만들어졌으며 다른명칭으로정통의학의부족한부분을보 충해준다는의미로보완의학 (complementary.5) medicine) 이라고도한다 외국의경우 서양의학을제외한한의학을포함한모 든의학을보완대체의학으로정의하는 반면우리나라와중국에서는한의학이 정통의학으로받아들여지고있기때문에 서양의학과한의학을제외한모든비정 통의학으로정의할수있다 6). 현재자궁내막증의수술과약물치료 는재발과부작용의한계점이있다. 이에여성의골반통을야기하는주요 원인중하나인자궁내막증에대하여국 외논문검색을통하여보완대체의학적 연구에대해살펴보고자한다. Ⅱ. 硏究方法 1. 연구대상논문선정 http://www.pubmed.gov 를이용하였다. 검색어는 endometriosis, CAM(complementary and alternative medicine), acupuncture, herbal, complementary treatment, alternative treatment 를지정하였다. 2. 연구대상의출판기간 검색된논문의출판기간은 1989년 8월 부터 2009년 7월 11 일이었다. 3. 연구방법 위의방법을통하여논문을검색하여 본연구의주요목적인자궁내막증의치 료를위해이용되고있는보완대체의학 과관련된논문 29 편을선별하였다. 1) 자궁내막증에대한 in vitro 연구논문 2편 실험 2) 자궁내막증에대한 in vivo 실험연 구논문 문 3) 19편 8편 자궁내막증에대한임상적연구논 Ⅲ. 硏究結果 1. 자궁내막증에대한 in vitro 실험 84
The Journal of Oriental Obstetrics & Gynecology Vol.22 No.4 November 2009 연구논문 총 29편의논문중 2편의논문이 in vitro 실험연구에해당하였다. Cell line 은 CCL5, SE-1, COUP-TF, 17-β -HSD1, 17-β-HSD2 가사용되었다. 각 논문의주요내용은 Table 1 과같다. Table 1. In vitro studies on endometriosis in CAM Author Cell line Medication Result Wieser F et al 7) CCL5 extract of 1 decreased cell proliferation herbal mixture SF-1, COUP-TF, Li A SLW( 三稜丸 ) 1 SF-1,17-β-HSD1 was decreased et al 8) 17-β-HSD1, 加味三棱丸 2 COUP-TF,17- β-hsd2 was increased 17-β-HSD2 2. 자궁내막증에대한 in vivo 실험연 구논문 29편의논문중 9편이 in vivo 실험연 구논문에해당되었다. 모두쥐를대상 으로실험을시행하였으며침을이용한 연구가 1 편, 단미를사용한연구가 1 편, 복합처방을사용한연구가 5 편, 한약과 양약을비교한연구가 2편에해당하였 다. 침과뜸, 三稜단일추출물, 异位寧, 小柴胡湯, 祛瘀解毒方, 香桂丸, 內异方, 化瘀補腎湯 등의복합처방을이용하여 VEGF, TNF- α, MMP-2, IL-6, IL-8, E2 의변화에대해연구하였다. 국내에서 黃芩, 半夏, 蒲公英, 當歸芍藥散, 當歸調 血飮, 隔下逐瘀湯, 加味紅藤湯, 加味歸朮 破癥湯, 溫經湯, 桃紅四物湯 연구과비교하여모두 등을이용한 活血祛瘀製를활 용한경향을보였으며黃芪, 化瘀補腎湯, 八珍湯 등 補益製를이용한연구도보였 다. 특이할만한점은침과뜸을사용한 연구가 1례있었으며복합처방과양약을 비교한연구가있었다는점이다. 각연 구의주요내용은 3. 문 Table 2 와같다. 자궁내막증에대한임상적연구논 29편의논문중 18편이임상논문에해 당되었다. 임상실험연구에서는침, 內 异, 丹蔘과莪朮, Pycnogenol, 香稜丸, 抗 异種玉湯, 調免化瘀湯, 祛瘀解毒方, 异位 寧, 桂枝茯笭丸, 大黃 桃仁 鱉甲의추출 물등을이용한연구가있었다. 국내에서 加味十全湯, 歸朮破癥湯, 全生活血湯등과 침구치료를이용한임상연구논문과비교 하여 活血祛瘀製를이용한경향은비슷 하지만국내임상연구논문에비해논문 당연구대상의수가평균 60명으로많았 으며 19례중 7례에서비교대조군의연구 방법을사용하였으며 Danazol, Tamoxifen, Gn-RHa 등양약과효능을 비교한연구논문은 19례중 10례로보다 객관성있는연구결과를보여주었다. 각 연구의주요내용은 Table 3 과같다. 85
Table 2. In vivo studies on endometriosis in CAM Table 3. Clinical studies on endometriosis in CAM. No. of Author Treatment patient Dura-tion Wayne PM et al. 18) Acupuncture 18 8 weeks Yan H et al. 19) Sun YZ et al. 20) Wu SZ et al. 21) Cai L et al. 22) Kohama T et al. 23) Acupuncture Danazol Acupuncture (ShuMu point 兪募穴 ) Danazol Neiyi pill* Neiyi enema Danazol Dan'e mixture ( 丹蔘, 莪朮 ) Pycnogenol ( 프랑스해안소나무추출물 ) 66 90 58 189 58 Author Treatment Result Chen YF 9) electro-acupuncture 1 reduced EMs tissue(p<0.05) Moxibustion 2 down-regulates MMP-2 level(p<0.05) Qu F 10) et al. Yiweinig Recipe* 1 reduced MMP-2, COX-2 Qu F 11) et al. Yiweinig( 异位寧 ) 1 reduced TNF- α, IL-6, IL-8(P>0.05) Zheng H 12) et al. XiaochaihuTang( 小柴胡湯 ) 1 inhibited ectopic endometrial growth(p<0.01) Li XL 13) et al.. Quyu Jiedu( 祛瘀解毒方 ) 1 decreased TNF- α, IL-6 (P<0.05) Chen Y et al. 14) Sanleng pellet( 三稜 ) 1 reduce VEGF, TNF-α Tang YJ et al. 15) Xianggui pill( 香桂丸 ) 1 decreased TNF- α, IL-8 Yu C et al. 16) Neiyifang 1 reduced weight of tissue, macrophage 2 reduced IL-10 1 inhibit the growth of endometrial Hong M 17) TCTS( 化瘀補腎湯 ) transplants, which is related with serum et al. hormone, especially E2. * : 异位寧 : 赤芍藥, 鬱金, 天麻, 黃芩, 薏苡仁, 柴胡, 金銀花, 蜈蚣 : 內异方 : 丹蔘, 血竭, 三稜, 莪朮, 桃仁, 三七根, 當歸, 桂枝, 香附子, 牛膝等 3menstrual cycle 9 months 48 weeks Result 1 pain score reduced 62% 2 reduction in pain persisted 6 months 1 effective rate was 97.0% in acupuncture treatment group and 72.7% in the Danazol group 2 E2 was decreased, Hb, RBC, BPC increased 1 Shu-Mu point combination group was superior to other two groups(routine needling group, Danazol) in improvement of dysmenorrhea, irregular menstuation, lumbago and sacrodynia, anus engorge, etc. (P<0.01) 2 CA125 in the Shu-Mu point combination group significantly decreased (P<0.01). 1 Combined therapy of NP and NE could improve the curative effect on endometriosis, and without obvious effects on serum levels of EMAB and CA125. 1 39 cases(20.6%) were cured, 67 cases(35.4%) were markedly effective, 67 cases(35.4%) were effective, and 16 cases(8.4%) were ineffective. 1 Treatment with Pycnogenol slowly but steadily reduced the symptom scores 2 CA-125 decreased 86
The Journal of Oriental Obstetrics & Gynecology Vol.22 No.4 November 2009 Gn-RHa Yang CB et al. 24) Xianglingwan 54 Lu XN et al. 25) Zg F et al. 26) Lian F et al. 27) Kangyi Zhongyu Decoction (KZD) ( 抗异種玉湯 ) GnRH-a Tiaomian Huayu ( 調免化瘀湯 ) Quyu Jiedu Recipe(QJR) ( 祛瘀解毒方 ) gestrinone Yiweinig (YWN) Yang DX et al. 28) ( 异位寧 ) gestrinone (GT) Keishibukuryo-gan Tanaka T 29) ( 桂枝茯笭丸 ) Wu Y et al. 30) chinese herb danazol Li J et Neiyi( 内异 ) al. 31) tamoxifen Liu J et al. 32) Neiyixiao (NYXR) danazol 75 66 50 52 7 52 45 103 3 mens cycle 3 months 6 months 12 weeks 1 CA125 reduced 2 The symptom of dysmenorrhea also reduced 1 The score of dyspareuria in KZD group and KZD with GnRH-a group was lower than GnRH-a group (P<0.01) 2 Pregnancy rate in KZD with GnRH-a group was higher than others 3 EMAb was reduced in KZD with GnRH-a group (P<0.05) 1 Total effective rate was 86.4%, while the control group 66.7% (P<0.05). 1 In QJR group and gestrinone group the positive rate and MOD of VEGF expression lowered significantly than before treatment (P<0.05). 2 In QJR group and gestrinone group Ki-67 changed insignificantly and showed no significant difference (P>0.05). 1 Post-operational recurrence rate of endometriosis in the YWN group(5.0%) and the GT group (5.3%) showing insignificant difference. 2 The adverse reaction rate in the YWN group (10.0%) was lower than GT group (31.6%). 1 Inhibited Fas-mediated apoptosis in the cells 1 The shrinking rate and disappearance rate of the cysts, and markedly effective rate of combination(chinese herb,danazol) group were obviously higher than chinese herb group and danazol group (P<0.05,P<0.01). 2 Pregnancy rate of combination group was higher than danazol group (P<0.05). 1 In Neiyi group and tamoxifen group NK cells and the count of T-suppressor cells were significantly increased(p<0.01), the count of T-helper cells, the secretion of interleukin-ii and TH/TS ratio were significantly reduced (P < 0.01). Over 50% of the cases whose EmAb was positive eventually turned to negative. 2 There was no significant difference between Neiyi group and tamoxifen group. 1 By tonifying Kidney and removing blood stasis, NYXR is multi-effective and being one of effective methods in clinical practice for treatment of endometriosis. 2 There was no significant difference in effect between the NYXR group and the danazol group in the relief of dysmenorrhea and degradation of prostaglandin (P>0.05). 3 The effect of NYXR in regulating endocrine and immunity was better than danazol. 87
Neiyi 1 PGF2-α and PGE2 markedly dropped, while Wang D 3 et al. 33) ( 内异 : 大黃 48 that of 6-keto-PGF1- α, β-ep, and HYP significantly months, 鱉甲, 桃仁 ) elevated Yu CQ nei-yi recipe et al. 34) 1 β-endorphin level significantly reduced ( 内异方 ) Xu LF gossypol 1 gossypol administered orally was effective in et al. 35) 12 ( 木花 ) endometriosis patients * : 內异丸 : 丹蔘, 血竭, 三稜, 莪朮, 桃仁, 三七根, 當歸, 桂枝, 香附子, 牛膝等 : 内异灌肠液 : 丹蔘, 血竭, 三稜, 莪朮, 赤芍藥, 虎杖根等 : 香稜丸 : 三稜, 靑皮, 陳皮, 莪朮, 枳殼, 枳實, 蘿葍子, 香附子, 黃蓮, 神麯 ( 炒 ), 麥芽 ( 炒 ), 鱉甲, 桃仁, 砂仁, 木香, 甘草, 檳榔, 山査等 内异消湯 : 三稜, 莪朮, 免絲子, 水蛭, 穿山甲等 Ⅳ. 考察 자궁내막증은자궁내막조직이자궁밖 에존재하여증식하는질환으로월경통, 만성골반통, 성교통, 불임과같은다양한 증상을보인다. 이질환은가임기여성 인구의 6-20% 에서발견되고, 자궁내막 증을갖고있는여성의불임은 10-30% 까지다양하게보고되고있다. 자궁내막 증의정확한원인과병태생리는밝혀지 지않았지만유전적요인, 호르몬적요 인, 환경적요인등과함께면역학적요 인이중요한병인으로제시되고있다. 치료는약물요법, 수술요법또는이를 병행하는방법등이있으며증상이나진행 정도가미약한경우에는기대요법을실시 할수도있다 1). 약물치료는 progesterone, danazol 등과같은항에스트로겐작용을 지닌약물들과일시적인가폐경상태를 만드는 GnRH agonist 같은약물들및 가임신상태를만드는경구피임제등이 사용되는데체중증가, 유방축소, 다모증, 위축성질염, 질출혈, 질건조증, 안면홍 조, 여드름, 골다공증, 우울증, 피로등의 부작용이보고되고있다 2,3). 또한수술 적치료는재발율높아임 36) 의보고에 따르면수술만한경우는수술후 이내에약 1년 50% 에서증상이다시재발되 는것으로보고되고있다. 또한복강경 수술후에는혈관, 위장관계, 비뇨기계, 헤르니아, 전기적손상등의합병증이나 타날수있다 37). 따라서비침습적인보완 대체의학적치료법은부작용이적으면서 가임기여성에게효과적인치료법이될 수있을것이다. 그리고자궁내막증의 원인중면역학적요인에대해서뚜렷한 치료법이없는서양의학적치료법에비 해 補益製를이용한한의학적치료는강 점을가질수있을것이다. Pubmed 에나타난자궁내막증의보완 대체의학적치료에대한논문을살펴본 결과 in vivo논문의경우 cell line으로 CCL5, SF-1, COUP-TF, 17-β-HSD1, 17-β-HSD2 을사용하였으며단미, 복합 처방을이용하여 cytokine을조절하여 자궁내막증에유의한효과가있음을밝 혔다. 국내의자궁내막증에대한실험 연구는주로 MCP, TNF- α, IL-2, IL-6, IL-8, IL-10을사용하여 cell line의종류 에차이가있었으나 cytokine을측정하 여효과를밝혔다. In vivo 실험연구논 문은처방으로 活血祛瘀製를활용한경 88
The Journal of Oriental Obstetrics & Gynecology Vol.22 No.4 November 2009 향을보이면서化瘀補腎湯의補益製를 이용한연구가있었으며이는국내의黃 芩 38), 蒲公英 39), 黃芪 40), 當歸芍藥散 41), 芎 歸調血飮 42), 隔下逐瘀湯 43), 加味紅藤湯 44), 加味歸朮破癥湯 45), 溫經湯 46), 桃紅四物湯 47) 을이용한연구와공통점을가진다. 연 구에서모두 MMP-2, COX-2, TNF- α, IL-6, IL-8 등의 cytokine 의변화를측정 하여효과를밝혔다. 그러나국내에는 침법을이용한연구가없는데반해 Pubmed에서는침법을이용한연구가 1 편있었다. 자궁내막증에대한임상연구 논문은총 18편으로복합처방을이용한 연구가주를이루었으며, 환자의주관적 인통증변화, 혈청의 E2, CA-125의변 화등을측정하여자궁내막증에유의한 효과가있음을밝혔다. 특이한점은국 내연구논문에비해연구대상의평균 60 명으로대상의수가많으며비교대조군 연구를하였으며양약과비교하여부작 용과재발이적음을밝힌논문들이있다 는것이다 19-21,25,27,28,30-32). 임 39) 의보고에따르면자궁내막증이 의심되는환자에서진단혹은치료목적 의골반경수술을시행한후에자궁내막 증의재발을방지하기위한약물치료가 권장되고있다고한다. 국내에서도자궁 내막증의치료에대해한방치료와양방 치료의효과를비교하여한방치료의우 수성을밝히거나약물치료시발생하는 부작용을줄일수있는한방치료법에대 한연구가필요하다고생각된다. Ⅴ. 結論 자궁내막증에대한보완대체의학적치 료에대한 Pubmed의논문을분석하여 아래와같은결론을얻었다. 1. 자궁내막증에대한 in vitro 실험연구 논문은 2편으로 cell line으로 CCL5, SF-1, COUP-TF, 17-β -HSD1, 17-β -HSD2 을사용하였으며단미, 복합처 방을이용하여 cytokine을조절하여 자궁내막증에유의한효과가있음을 밝혔다. 2. 자궁내막증에대한 in vivo 실험연구 논문은총 9 편이었다. 처방을이용한 연구들은 活血祛瘀製를활용한경향 을보이면서化瘀補腎湯의補益製를 이용한연구가있었으며연구에서모 두 MMP-2, COX-2, TNF- α, IL-6, IL-8 등의 cytokine의변화를측정하 여효과를밝혔다. Pubmed에서는침 을이용한연구가 1 편있었다. 3. 자궁내막증에대한임상연구논문은총 18 편으로복합처방을이용한연구가 주를이루었으며, 환자의주관적인통 증변화, 혈청의 E2, CA-125의변화 등을 측정하여자궁내막증에유의한 효과가있음을밝혔다. 요약컨대자궁내막증의치료는수술적 치료의제한성및약물치료에따른부 작용을고려했을때비침습적이며부작 용이적은보완대체의학적인치료방법이 효과적일것으로사료된다. Pubmed의에 서검색한자궁내막증의보완대체의학적 치료의연구동향을고찰해볼때, 향후 국내연구에서는한약과양약을이용한 비교연구및병용투여에대한연구가 필요하며침등을이용한다각적인연구 가필요하다고생각된다. 89
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