ORIGINAL ARTICLE Korean J Obstet Gynecol 2012;55(12):947-952 http://dx.doi.org/10.5468/kjog.2012.55.12.947 pissn 2233-5188 eissn 2233-5196 THE ROLE OF GONADOTROPHIN RELEASING HORMONE AGONIST FOR THE TREATMENT OF SCAR ENDOMETRIOSIS So Yun Park, MD, Sa Ra Lee, MD, Hye Won Chung, MD Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, Seoul, Korea Objective To investigate the characteristics and to define the most effective diagnosis and treatment option for the scar endometriosis resulting from abdominal incision or episiotomy. Methods Medical records of thirty women with scar endometriosis who underwent mass excision between 1996 and 2008 in our hospital were reviewed retrospectively. Data on the age, parity, surgical history, symptom, menstrual history, characteristics of the mass, preoperative diagnosis, treatment method and recurrence were analyzed. Results Scar endometriosis were developed after C ㅊ esarean section in 24 patients and episiotomy in 6 patients. Nearly all patients presented with a palpable mass with or without cyclic pain and mean duration of symptom was 23.8 months. Preoperative imaging study was performed in 14 patients, however there was no one whose preoperative imaging result was endometriosis. All scar endometriosis was completely excised with surrounding tissue. Gonadotrophin releasing hormone (GnRH) agonist was administered in 13 patients pre- or postoperatively. Recurrence of scar endometriosis after wide mass excision was noted in 4 patients (13.3%) who did not receive GnRH agonist therapy pre- or postoperatively. Conclusion This study supports that scar endometriosis is a result of the transplantation of endometrial tissue during procedures. The contribution of the imaging studies seems to be limited, so surgeon could perform mass excision for diagnosis and treatment with clinical history and physical exam without performing imaging study especially in for small scar endometriosis. Surgical excision accompanied by pre-, or postoperative GnRH agonist therapy may be helpful option for the prevention of recurrence however, we could not find any statistical significance in the effectiveness of GnRH agonist treatment. Keywords: Endometriosis; Excision; Recurrence; GnRH agonist 자궁내막증은자궁내막조직이자궁외에서증식하는질환으로대부분은골반내장기에서발생하나약 1%-2% 는골반외에서발생하고, 0.03%-1.7% 는외과적수술후에발생하는절개반흔자궁내막증 (scar endometriosis) 이다 [1], 제왕절개술이나질식분만뿐아니라자궁절제술, 골반경수술및양수천자술후에도발생이보고되고있는데 [2,3]. 복벽절개반흔자궁내막증의경우가장많은수는자궁절개술후에발생하는경우로자궁절개술후약 0.2% 에서보고된다 [4]. 절개반흔자궁내막증의발생기전으로는의인성요인에의한착상, 즉수술중수술기구에묻은자궁내막조직이절개부위에착상하여발생한다고생각되고있으며표준치료는종양주위를넓게수술적제거 (wide surgical excision) 하는것인데약 9.1% 의재발률이보고된다 [4]. 한편절개반흔 Received: 2012.5.29. Revised: 2012.10.14. Accepted: 2012.10.17. Corresponding author: Sa Ra Lee, MD, PhD Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea Tel: +82-2-2650-6011 Fax: +82-2-2647-9860 E-mail: sarahmd@ewha.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2012. Korean Society of Obstetrics and Gynecology WWW.KJOG.ORG 947
KJOG Vol. 55, No. 12, 2012 자궁내막증의수술후재발방지를위해성선자극호르몬유리호르몬작용제 (gonadotrophin releasing hormone agonist, GnRH agonist) 투여를병합하는것의효과에대해서는아직정립된바가없다. 이에본연구에서는복벽절개반흔및회음부절개반흔에발생한종물로수술후병리조직검사에서절개반흔자궁내막증으로확진되어추적관찰중인환자 30예를후향적으로분석하여절개반흔자궁내막증의임상특징및가장효과적인진단및치료법에대해알아보고자하였다. 연구대상및방법 1996년 1월 1일부터 2008년 12월 31일까지복벽절개반흔및회음부절개반흔에발생한종물로종괴절제술을시행하고, 병리조직검사에서절개반흔자궁내막증으로확진되었던환자중 12개월이상추적관찰이되었던환자 30예를대상으로하였다. 각연구대상자의의무기록에서절개반흔자궁내막증을진단받았던당시의연령, 분만수, 생리력, 생리통여부, 종물과관련된증상, 질식분만기왕력, 자궁수술의기왕력, 수술전진단에사용된영상검사의종류, 수술전잠정진단명, 종괴의수와크기및위치를비롯한수술소견, 혈중 cancer antigen (CA) 125 수치, 수술전후의 GnRH agonist 치료의여부및횟수, 12개월이상의추적관찰에서자궁내막증의재발여부를분석하였다. 통계적분석은 student t test와 Fisher s exact test를이용하였으며, P-value 0.05 미만을통계적으로유의하다고판정하였다. 결과 병리조직학적으로절개반흔자궁내막증이확진된환자총 30명중, 복벽절개반흔자궁내막증환자는총 24명이었고회음절개반흔자궁내막증환자는총 6명이었다. 복벽절개반흔자궁내막증의경우, 총 24 예중 1예 (4.2%) 만이복식전자궁절제술후발생하였고나머지 23예 (95.8%) 는모두제왕절개술후발생한사례였다. 복벽절개및회음절개시기부터증상발현까지의기간은평균 23.8개월이었고증상별로분류하면, 반복적으로생리기간에발생하는절개반흔부위의통증혹은종물의크기증가를주소로내원한경우가가장많았고 (60.0%), 생리기간과관계없이절개반흔부위에촉지되는종물 (36.7%), 무증상이다가외래진찰중의사가우연히발견한경우 (3.3%) 순이었다 (Table 1). 생리통및골반내자궁내막증동반여부에대해서는중등도이상의생리통이있는경우는 63.3% 였으며, 골반초음파는총 24명의환자에서시행하였는데난소및골반장기의자궁내막종소견이있는경우는한예도없었다 (Table 1). 총 10예에서혈청 CA 125 수치를검사했는데, 수치가상승된경우 (>35 U/mL) 는 2예로, 각각 91 U/mL, 39.8 U/mL였고모두복벽절개반흔자궁내막증환자였는데혈액검사당시자궁내막증외에혈청 CA 125 수치가상승될수있는다른원인, 즉자궁근종, 자궁선근증, 골반염, 혹은자궁외임신의소견등은보이지않았다. 절개반흔자궁내막증의종물의개수는대부분 (80%) 에서단일종물 의양상이었으나복수 (2 개 ) 인경우도 6 예 (20%) 있었다 (Table 2). 자궁내 막증의발생위치별로분류하면회음절개반흔자궁내막증은모두피하 지방층에서발생하였으나, 복벽절개반흔자궁내막증의경우, 피하지방 층이 58.4%, 직복근 (rectus abdominis) 의근막층이 20.8%, 직복근까지 침범한경우가 20.8% 로확인되었다. 복벽절개반흔과회음절개반흔자 궁내막증의평균크기는각각 678.6 mm 2 과 144 mm 2 으로복벽절개반 흔자궁내막증의경우는가장큰경우가직경 6.0 cm 였다. 수술전영 상검사를시행한경우는복벽절개반흔종물에서총 14 예 (58.4%) 에서 있었는데, 복부초음파와복부컴퓨터단층촬영 (computed tomography, CT) 을시행한경우가각각 7 예 (29.2%) 씩이었다. 수술전잠정진단명 은회음절개반흔에발생한경우는대부분 (83.3%) 에서절개반흔자궁내 막증으로잠정진단되었으나, 복벽절개반흔에발생한 24 예의경우, 가 장많은경우 (41.7%) 에서유건종 (desmoid tumor) 으로잠정진단되었고 자궁내막종으로잠정진단했던경우는 6 예 (25.0%) 에불과했으며, 절개 Table 1. Clinical characteristics of scar endometriosis patients Characteristic Abdominal incision scar endometriosis (n = 24) Episiotomy scar endometriosis (n = 6) Mean age 35.0 33.5 Gravida/Para 2.3/1.8 2.5/1.7 No. of previous C section/vd 1.7/0 0/1.7 Symptom No symptom 1 (4.1) 0 Palpable mass 10 (41.7) 1 (16.7) P ain or swelling during menstruation 13 (54.2) 5 (83.3) Duration of symptom (mo) 17.4 59 Interval time (mo) a 68.7 42.2 Menstruation history Regular interval 23 (95.8) 6 (100) Duration (day) 5.0 4.0 Amount Small 3 (12.5) 0 Moderate 20 (83.4) 6 (100) Large 1 (4.1) 0 Dysmenorrhea Mild 9 (37.5) 2 (33.3) Moderate 10 (41.7) 1 (16.7) Severe 5 (20.8) 3 (50) Values are presented as mean or number (%). C section, Cesarean section; VD, vaginal delivery with episiotomy. a Interval time, months from last Cesarean section and episiotomy to symptom of scar endometriosis. 948 WWW.KJOG.ORG
So Yun Park, et al. Scar endometriosis 헤르니아 (incisional hernia) 와염증성낭종 (inflammatory cyst) 을포함 한기타종물로진단한경우가 8 예 (33.3%) 였다 (Table 2). 30 예모두수 술시전신마취하에 1 cm 이상의경계를둔광범위절제술을시행하였 Table 2. Characteristics of scar endometriosis Characteristic No. of mass Abdominal incision scar endometriosis (n = 24) Episiotomy scar endometriosis (n = 6) One 19 (79.2) 5 (83.3) Two 5 (20.8) 1 (16.7) Size of mass (mm 2 ) a 678.6 144 Location of mass Subcutaneous layer 14 (58.4) 6 (100) Fascia layer 5 (20.8) 0 Muscle layer 5 (20.8) 0 Preoperation diagnosis Endometriosis 6 (25.0) 5 (83.3) Desmoid tumor 10 (41.7) 0 Others 8 (33.3) 1 (16.7) U sed preoperative imaging technique US 7 (29.2) 0 CT 7 (29.2) 0 None 10 (41.6) 6 (100) Values are presented as number (%). US, ultrasonography; CT, computed tomography. a Size of mass (mm 2 ), width of mass (mm) height of mass (mm). Table 3. Recurrence rate according to combined GnRH agonist treatment Preoperatively GnRH agonist Postoperatively No. of patients Recurrence n (%) None None 17 4 (13.3%) 3 times 5 0 >3 times 5 0 3 times None 0 3 times 2 0 >3 times 0 >3 times None 0 3 times 1 0 >3 times 0 P value=0.10 by Fisher s exact test. The recurrence rate between patients who underwent GnRH agonist therapy and patients who did not underwent GnRH agonist therapy pre or postoperatively. GnRH agonist, gonadotrophin releasing hormone agonist. 는데수술전후에 GnRH agonist 를투여한경우는 13예 (43.3%) 에서있었으며, 투여시기및횟수별로분석한결과는 Table 3과같다. 수술후최소 1년이상의추적관찰기간동안재발한경우는 4예 (13.3%) 로모두수술전후에 GnRH agonist 를사용하지않은군이었다 (Table 3). 절개반흔자궁내막증환자에서 GnRH agonist 사용의재발방지효과를판단하기위해, GnRH agonist 를한번이라도사용한군과한번도사용하지않았던군으로나누어재발률을분석한결과, 통계적으로유의한재발률의차이는없었다 (P>0.05). 고찰 절개반흔자궁내막증은제왕절개술후에발생하는경우가가장많아제왕절개술후절개반흔자궁내막증의발생빈도는 0.03%-0.2% 이고 [2,5,6], 회음절개반흔에발생하는경우는더낮은빈도를보인다 [7]. 근래에는복강경수술의빈도가급증하여매우드문경우이긴하나, 복강경시투관침 (trocar) 이삽입되었던부위반흔에자궁내막종이발생한경우도보고되었고 [3], 심지어는서혜부탈장수술이나양수천자이후에도보고된바있다 [8]. 그런데본연구에서는복강경수술이나양수천자이후에발생한자궁내막증의경우는없었고대부분이 (96.7%) 제왕절개술과회음절개후에발생한것이었다. 절개반흔자궁내막증의발생기전으로는기계적전이설 (mechanical transportation), 즉자궁이나나팔관수술시에자궁내막세포가노출된복벽이나회음절개부위에부착하여증식하는것이가장널리받아들여지고있다 [9]. 호발연령은 21-46세로보고되는데 [9,10], 이는골반내자궁내막증의호발연령과같고, 본연구에서도호발연령이 34.3세로이들연구결과와일치하였다. 제왕절개술후절개반흔자궁내막증이발생하기까지는적어도 2 년이상의시간이걸리는것으로보고되었고 [11], 본연구에서는평균 5년 8개월후에발생하였다. 회음절개반흔자궁내막증의경우, 본연구에서는평균 3.5년후에발생하여 Koger 등 [12] 의연구에서평균 4.8 년이라는보고와일치하였다. 증상은대부분절개반흔부위의압통을동반한종물의크기증가로나타나며 [11,13,14], 본연구에서도월경주기에일치하여발생하는절개반흔부위통증및종물의크기증가를주소로하는경우가 18예 (60%) 로가장많았다. 절개반흔자궁내막증의발생위험인자로는임신초기의자궁절개술, 알코올섭취, 월경과다증이보고된바있으나 [15], 국내보고에서는월경기간이긴경우에유의한차이를보인다고하였으며 [16], 본연구에는정상월경주기및월경양을보이는경우가많아 (87%) 절개반흔자궁내막증의위험인자로월경관련인자를규정짓기는어렵겠다. 골반내자궁내막증과의연관성에대해서는절개반흔자궁내막증환자의 26%-50% 에서골반내자궁내막증을동반한다는보고가있었으나 [17,18], 본연구에서는총 30명의환자중 24명에서시행한수술전골반초음파에서골반내자궁내막증이확인된경우는한예도없었다. 그러나진단적골반경을시행하진않았으므로골반내자궁내막증과절개반흔자궁내막증과의연관성에대해서는명확한결론을도출하기어렵지만, 본연구에서중증이 WWW.KJOG.ORG 949
KJOG Vol. 55, No. 12, 2012 상의생리통이있는경우가 19예 (63.3%) 였고, 이중 8예 (26.7%) 는중증의생리통이있었던것을고려하면골반내자궁내막증과의연관성에대한가능성을완전히배제할수는없겠다. 한편혈중 CA 125를측정하는것이절개반흔자궁내막증에있어서진단및추적관찰에도움이된다는보고가있었으나 [19], 본연구에서는 CA 125수치를검사한 10명중 2명에서만정상보다높은 CA 125수치를보였는데, 대상자수가너무적어절개반흔자궁내막증에대한 CA 125 검사의효용성와의연관성을결론내리기는어렵겠고추후보다많은수의대상자에서연구가된다면이에대한결론을내릴수있겠다. 진단은대개특징적인병력, 즉절개반흔에발생한종물이월경시에반복되는통증혹은종물크기의증가가있을때의심하여영상진단통해잠정진단할수있으나, 특히복부절개부위에발생하는절개반흔자궁내막증의경우, 초음파나 CT, MRI 등의영상진단기법의진단적효용성에대해서는논란중이다 [2,5,11,20]. 대부분의경우그효용성은낮다고보고되고있는데 [5,20], 영상검사에서복벽의종물을주소로내원하게되는다른질병과의감별이어렵기때문이며, 본연구에서도복벽절개반흔자궁내막증에서수술전영상진단을시행한총 14예 (58.3%) 에서자궁내막증의소견이나온경우는없었고, 3 cm 이하의작은종물인경우, 영상검사에서복벽의종물이발견되지않은경우가 4예 (28.6%) 있었다. 한편회음절개반흔의자궁내막증에서는모든예에서수술전영상검사를시행하지는않았는데병력청취와임상진찰에서항문주위농양 (perianal abscess) 으로잠정진단되었던 1예를제외하고는나머지 5예 (83.3%) 에서모두자궁내막증으로수술전잠정진단되었다. 즉절개반흔자궁내막증의경우, 특히크기가작은경우에는영상진단기법이잠정진단을내리는데많은도움이될것을기대할수는없으나종물내장 (viscera) 의존재유무를확인하거나종물의크기및항문괄약근을비롯한주위조직으로의침범정도를확인하여수술시이식편 (graft) 을사용하여보강할지의여부등을결정하는등, 수술의범위를정하는데에는도움이될수있겠다. 특히 MRI는 CT에비해고해상도의영상으로근육과피하지방층사이의작은병변과자궁내막종내의출혈을감별하는데도움이된다 [11]. 절개반흔자궁내막증의표준치료는종물을포함하여최소 1 cm 이상의주위조직을절제 (wide excision) 하는것이며 [21,22], 내과적치료로경구피임약, 프로게스토젠, 에스트로겐- 프로게스토젠의병합요법, 그리고 GnRH agonist 등의약물요법이시도되었으나약물단독치료는일시적증상완화효과만기대할수있으며 [6], 자궁내막증이통증, 종창, 출혈등의증상을일으키게될뿐아니라투명세포암과의연관성도잘알려져있으므로수술적제거가필수적으로생각되고있다. 본연구결과에서도 GnRH agonist 의사용과절개반흔자궁내막증의수술적치료후재발과의관계에대한분석 (Table 3) 에서 GnRH agonist 의사용여부와재발과는유의한상관관계가없었으므로, 이상에서본연구결과를종합하면, 병력청취와임상진찰에서절개반흔자궁내막증이의심될때, 종물의크기가 3 cm 이상으로큰경우에초음파나 MRI 등의영상기법이진단에도움이될수있고, 치료는주위조직을포함하여광범위하게종물의수술적제거를시행하는것이가장적합한치료계획이라고할수있겠으며 GnRH agonist 의투여는재발억 제에대한효과적인치료법이라고할수는없겠다. 국내에서도절개반 흔자궁내막증을증례보고형식으로발표되긴하였으나 [13,23-26], 이 를임상적으로고찰한논문은거의없고, 특히본연구에서처럼절개반 흔자궁내막증의임상적특징및가장적합한진단및재발방지를위 한치료법에대해서정리한논문은전세계적으로찾아보기힘들다. 이 에본연구가절개반흔자궁내막증의진단및치료에대한참고자료가 될수있기를기대하며앞으로대규모의무작위대조군연구가시행된 다면 GnRH agonist 의재발방지효과에대한명확한지침을제시할수 있겠다. References 1. Firilas A, Soi A, Max M. Abdominal incision endometriomas. Am Surg 1994;60:259-61. 2. Bumpers HL, Butler KL, Best IM. Endometrioma of the abdominal wall. Am J Obstet Gynecol 2002;187:1709-10. 3. Wakefield SE, Hellen EA. Endometrioma of the trocar site after laparoscopy. Eur J Surg 1996;162:523-4. 4. Gaunt A, Heard G, McKain ES, Stephenson BM. Caesarean scar endometrioma. Lancet 2004;364:368. 5. Roncoroni L, Costi R, Violi V, Nunziata R. Endometriosis on laparotomy scar. A three-case report. Arch Gynecol Obstet 2001;265:165-7. 6. Chatterjee SK. Scar endometriosis: a clinicopathologic study of 17 cases. Obstet Gynecol 1980;56:81-4. 7. Gordon PH, Schottler JL, Balcos EG, Goldberg SM. Perianal endometrioma: report of five cases. Dis Colon Rectum 1976;19:260-5. 8. Kaunitz A, Di Sant Agnese PA. Needle tract endometriosis: an unusual complication of amniocentesis. Obstet Gynecol 1979;54:753-5. 9. Brenner C, Wohlgemuth S. Scar endometriosis. Surg Gynecol Obstet 1990;170:538-40. 10. Hasson HM. Incidence of endometriosis in diagnostic laparoscopy. J Reprod Med 1976;16:135-8. 11. Lee SE, Jeong JE, Joo JK, Lee KS. Clinicopathologic review of extrapelvic endometriosis. Korean J Obstet Gynecol 2012;55:83-8. 12. Koger KE, Shatney CH, Hodge K, McClenathan JH. Surgical scar endometrioma. Surg Gynecol Obstet 1993;177:243-6. 13. Park TS, Her IS, Lee HW, Jo YY, Park JB, Kang HJ. Two cases of endometriosis at the subcutaneous tissue of the abdominal scar after cesarean section. Korean J Obstet Gynecol 2004;47:752-8. 950 WWW.KJOG.ORG
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KJOG Vol. 55, No. 12, 2012 절개반흔자궁내막증의치료에서성선자극호르몬유리호르몬작용제의역할 이화여자대학교의학전문대학원산부인과학교실박소연, 이사라, 정혜원 목적복벽절개혹은회음절개술후발생하는절개반흔자궁내막증환자의임상특징및가장적합한진단및치료법에관해알아보고자하였다. 연구방법 1996년부터 2008년까지본병원에서절개반흔자궁내막증으로종물절제술을받은 30명의환자를대상으로하여의무기록을바탕으로후향적으로분석하였다. 대상자의연령, 분만력, 수술과거력, 증상, 생리력, 종물의특성, 수술전잠정진단명, 치료법과재발에대해분석하였다. 결과절개반흔자궁내막증으로확진된환자 30명중, 복벽절개반흔자궁내막증환자는총 24명, 회음절개반흔자궁내막증환자는총 6명이었다. 증상은대부분에서주기적통증을동반하거나동반하지않는, 절개반흔부위의촉지되는종물이었고, 마지막수술시점부터증상발현까지의기간은평균 23.8개월이었다. 수술전영상검사를시행한경우는 14예였으나절개반흔자궁내막증으로진단된경우는한예도없었다. 모든경우에서종물을포함한광범위한절제를시행받았고성선자극호르몬유리호르몬작용제를투여받은경우는 13예였다. 재발은 4예 (13.3%) 에서진단되었고모든경우가수술전혹은수술후에성선자극호르몬유리호르몬작용제를투여받지않은경우에서였으나통계적으로유의한차이는없었다. 결론본연구결과에서절개반흔자궁내막증의발생기전이시술중의자궁내막의이식에의한것임을뒷받침하고있으며, 영상검사가진단에크게도움이되지않으며병력청취나임상진찰에서절개반흔자궁내막증이의심될때진단및치료를위해종물을제거하는것이필요하다. 성선자극호르몬유리호르몬작용제를수술전후에사용하는것은절개반흔자궁내막증의재발억제에도움이될가능성은있겠으나통계적으로유의한재발억제효과는없었다. 중심단어 : 자궁내막증, 절제, 재발, 성선자극호르몬유리호르몬작용제 952 WWW.KJOG.ORG