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1 ORIGINAL ARTICLE Korean J Obstet Gynecol 2011;54(8): pissn eissn PROGNOSIS OF ENDOMETRIOSIS AFTER SURGICAL TREATMENT IN ADOLESCENTS BELOW 20 YEAR AGE Na Young Sung, MD, Bong Seok Kim, MD, Yeon Jean Cho, MD, Youn Sil Choo, MD, Joo Myoung Kim, MD, Seung Heon Yang, MD Department of Obstetrics and Gynecology, Cheil General Hospital & Women s Healthcare Center, Kwandong University College of Medicine, Seoul, Korea Objective To evaluate the clinical characteristics and prognosis of surgically treated endometriosis in adolescent women below 20 year age. Methods A retrospective review was conducted on patients diagnosed endometriosis on operation below 20 year age at Cheil General Hospital between January 2001 and October Clinical characteristics, treatment results and follow-up data for 79 women were collected. Results The mean age at operation was 18.5 year age, and in 5 cases (6.3%) the operation was performed at 15 year age. Müllerian anomalies were accompanied in 6 cases (7.6%). Seventy-nine per cent of patients had pain associated symptoms such as dysmenorrhea, non cyclic pelvic pain, and gastrointestinal pain. Endometriosis was found to be stage I in 20.3% of patients, stage II in 7.6% of patients, stage III in 40.5% of patients and stage IV in 31.6% of patients. We could not find any recurrence in patients with stage I and II endometriosis, however patients with stage III and IV endometriosis showed recurrence rates of 15.6% and 28.0%, respectively, during the mean follow-up period (33.7 ± 28.5 months). During the 36-month follow-up, the cumulative proportion of subjects free from endometrioma recurrence was 82.5%, but the rate increased as the follow-up period was extended. Conclusion Endometriosis can occur in adolescents and the recurrence rate is higher in advanced stage. As endometriosis is a progressive disease, early diagnosis and treatment during adolescence may be necessary. Keywords: Endometriosis, Adolescent, Recurrence, Müllerian anomaly 자궁내막증은생리통, 골반통, 성교통, 배변통등의증상을나타내는부인과질환으로서가임기여성의 10-20% 에서발생한다 [1]. 이러한자궁내막증의청소년기및 20대초반여성의유병률에대한역학적인연구는드물지만어른이되어서자궁내막증을진단받은환자의약 66% 가이미 20세이전에골반통과같은증상이있었다고알려져있다 [2]. 생리통이나골반통은청소년기에도많이호소하는증상이나실제로이러한증상이특정질병과직접관련된증상인지임상적으로구분하기는어렵다. 생리통은청소년기에호소하는가장흔한증상중하나로서대부분은일차성생리통으로비스테로이드진통제 (non steroidal antiinflammatory drugs, NSAID) 나경구용피임제에반응을한다. 더욱이청소년기에는증상이있을때약물치료에어느정도반응을하는경우진단을위하여추가로수술을고려하는경우는많지않다. 하지만약물치료에반응을하지않는경우에는어떠한병인이있는지를생각해봐야하는데, 가장흔한질병이자궁내막증이다 [3]. 청소년기에만성골반통을호소하는경우자궁내막증의유병률은약 17-73% 로다양하게나타나 지만, 경우에따라서는복강경수술로도특별한병변을찾지못하는경우도많다 [4-6]. Received: Revised: Accepted: Corresponding author: Yeon Jean Cho, MD Department of Obstetrics and Gynecology, Cheil General Hospital & Women s Healthcare Center, Kwandong University School of Medicine, 1-19 Mukjeong-dong, Jung-gu, Seoul , Korea Tel: Fax: jeanjane@naver.com This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright Korean Society of Obstetrics and Gynecology 448

2 Na Young Sung, et al. Prognosis of endometriosis after surgical treatment in adolescents below 20 year age 뮐러리안관의기형으로월경유출로가막힌경우에자궁내막증이동반되는경우가청소년기에발견된자궁내막증의 40% 를차지한다는보고도있지만, 보고에따라서는약 1% 만이이러한기형과관련있다고하였다 [7,8]. 전반적으로뮐러리안기형을동반한자궁내막증의빈도는약 5-6% 로알려져있다 [2]. 최근발표에의하면자궁내막증과연관하여입원하는청소년들과 23 세이하의여성들의비율이자궁내막증으로외래방문하는환자의 20% 를넘어서는양상을보이고있으며, 자궁내막증의발견연령대가점점낮아지는양상을보인다 [9]. 실제로산부인과에대한인식이바뀌면서청소년을포함한여성들의병원내원율도증가하고있으며질병에대한관심도도높아지고있는실정이다. 청소년기를포함한 20대초반의자궁내막증환자는앞으로재발의가능성, 임신가능성뿐만아니라삶의질또한고려되어야하기때문에연구가필요하겠다. 국내외문헌검색상청소년기의자궁내막증에대한고찰은제한적이며최대 66명의환자들을대상으로한연구가있었고, 국내에서도 2001 년에 21세이하인 39명의환자를대상으로연구를한바있으나아직까지대규모연구는부족한실정으로지속적인연구가필요하다 [10,11]. 이에본연구에서는 2000년 1월부터 2010년 10월까지제일병원산부인과에서수술로서자궁내막증으로진단받은환자중에서 20세이하의청소년기여성을대상으로그임상양상, 예후및동반기형등을알아보고자한다. 본연구는 2000년 1월부터 2010년 10월까지본원에서수술후자궁내막증으로진단받은환자중에서 20세이하여성 79명을대상으로후향적으로조사하였다. 모든환자의수술당시나이, 체질량지수, 월경성향, 출산력, 재발여부등의임상적소견을조사하였으며의무기록에근거하여환자들의주된증상, 수술방법, 연령별분포, 진단당시임상적병기를조사하였으며, 자궁내막증의병기설정은 1996년개정된 revised American Fertility Society of Endometriosis (rafs) 병기분류체계에근거하였다 [12]. 수술방법은 69명에서복강경수술, 10명에서개복술을시행하였으며, 모든환자는수술전에환자의문진및이학적검사를시행하였으며초음파소견및동반질환의유무, 동반기형의유무, 이전약물치료의과거력, 수술후약물치료의여부, 수술당시의병기및수술방법, 추적관찰기간동안의재발및임신여부를조사하였다. 본연구에서재발의정의는기존의연구에근거하여초음파상원형의균일한저에코의경계가뚜렷하고유두상돌기가관찰되지않는낭종으로보이면서그크기가 2 cm 이상인경우로하였다 [13]. 수술당시낭종제거술, 골반유착박리및자궁내막증조직제거수술을시행하였으며수술후약물치료유무및방법, 수술후정기적초음파시행으로재발여부를보았다. 통계는 SPSS ver (SPSS Inc., Chigago, IL, USA) 을통해분석하였고 Student s t-test, Fisher s exact test를사용하였으며, 유의수준이 0.05 미만을통계적으로유의하다고하였고누적재발률은 Kaplan- Meier method를사용하였다. 본연구기간동안본원에서총 79명의여성이자궁내막증으로수술을받았다. 수술받은환자의평균나이는 18.5세이며, 평균체질량지수는 20.7 ± 3.1 kg/m 2 이었다. 환자군의나이분포및초경연령은 Table 1과같다. 11세에서 15세사이에수술받은환자는 5명으로 6.3% 를차지하였으며대부분은 16세이후에수술을받은것으로나타났다. 평균초경연령은 13.1 ± 1.3 세로초경전에수술을받았던경우는없었다. 수술을받게된주증상은 Table 2에요약하였는데, 가장흔한증상은생리통으로 49.4% 이었고, 비주기성골반통또는위장관계통의통증을호소하는경우도 30.4% 로약 79% 에서는통증과관련하여수술을받게되었다. 수술을받게된적응증을살펴보면자궁내막증을의심하고수술을한경우는 54.4% 이며, 자궁내막증이아닌다른양성종양을추정하고수술을한경우가 21.5% 이다. 그외에는악성이의심되는경우, 자궁기형이의심되는경우, 혈복강이있었던경우등등다양한이유로수술적치료를시행했음을알수있었다. Table 1. The distribution of the age at operation and menarche Age of operation no. (%) Age of menarche no. (%) (3.8) 10 4 (5.1) 15 2 (2.5) 11 4 (5.1) 16 5 (6.3) (17.7) 17 9 (11.4) (31.6) (12.7) (26.6) (17.7) (12.7) (45.6) 16 1 (1.2) Total 79 (100) 79 (100) 449

3 KJOG Vol. 54, No. 8, 2011 환자들의평균추적관찰기간은 33.7 ± 28.5개월이었으며, 수술당시의병기 (rafs stage) 는 I기 20.3% (16예), II기 7.6% (6예), III기 40.5% (32 예 ) 와 IV기 31.6% (25예) 였다. 병기 I, II인경우는추적관찰기간동안유의한재발이없었다. 병기 III, IV기인경우에는 15.6% (5예) 와 28% (7 예 ) 에서재발을하였으며이들의재발까지의평균기간은 36.2 ± 24.3 개월이었다. 수술후약물치료는 55.7% (44명) 에서시행하였으며, 생식샘자극호르몬분비호르몬작용제 (gonadotropin-releasing hormone [GnRH] agonist) 를사용한경우가 39명, 경구용피임약을사용한경우가 4명이었으며, 한명은수술후 danazol을사용하였다. GnRH agonist 를사용한경우보완치료를한경우는 19명으로약 48% 였다. Table 2. Symptoms and preoperative diagnosis before surgical treatment of endometriosis no. (%) Presenting Symptoms Dysmenorrhea 39 (49.4) Non cyclic pain 22 (27.9) Palpable mass 9 (11.4) Incidental fi nding 5 (6.3) Gastrointestinal pain 2 (2.5) Preoperative diagnosis Endometrioma 43 (54.4) Ovarian benign tumor a 17 (21.5) Ovarian malignancy 4 (5.0) Ovarian torsion 7 (8.9) Uterine anomaly 2 (2.5) Infl ammatory mass 1 (1.3) Hemoperitoneum 4 (5.1) Ectopic pregnancy 1 (1.3) a Ovarian benign tumor-except endometrioma. 환자들이재발되지않고추적관찰기간을지내는양상은 (recurrence free survival) Fig. 1A와같다. 추적관찰결과 24개월에 92.5%, 36개월에 82.5% 에서재발하지않았다. 다만환자들의추적관찰기간이길어질수록재발의빈도는점점높아짐을알수있었다. 병기별로보았을때병기 III기와 IV기간의재발률자체의차이는보이지않았다 (log rank test, x 2 =1.84; P = 0.175) (Fig. 1B). 재발한군과재발하지않은군을나누어비교해보았을때환자의나이, 초경연령, 체질량지수, 수술당시낭종의크기, 단측성여부는유의한차이를보이지않았다. 다만재발한군의추적관찰기간이긴것을알수있었다. 재발한경우수술당시의병기는높은경향을보였으며 (P = 0.005, likelihood ratio for trend), 수술후약물치료는크게재발여부와상관이없는것으로나타났다 (Table 3). 본연구에서뮐러리안관기형과관련된경우는총 6예로 Table 4에간단히요약하였다. 세예에서는중복자궁과일측성자궁내혈종이있어복강경으로단측자궁절제수술을시행하였으며두예에서는질의중격이있어서중격을제거하였다. 본연구는단일기관에서수술로서자궁내막증을진단받은환자들을대상으로추적관찰하여 20세이하청소년기환자들의자궁내막증임상양상및재발률을보았다는데의의가있다고본다. 청소년기및 20대초반에발생하는자궁내막증에대해서는아직까지잘알려져있지않다. 청소년기에는약물에반응을하지않는생리통이나골반통을호소하는경우그원인을찾기위해서바로침습적인수술을하지는않기때문에정확한임상양상을파악하기위한대규모연구를진행하는데제한이있기때문인것으로생각된다. 실제로본기관에서해당연구기간동안자궁내막증으로수술한경우는약 7,100여건에달하는데이중 20세이하청소년기의자궁내막증진단건수는 79건으로극히일부분을차지하였다 Recurrence-free subjects n= A Time after surgery (month) B Time after surgery (month) Fig. 1. (A) Cumulative recurrence of endometriomas during the follow up period. (B) Cumulative recurrence of endometriomas according to the stage of endometriosis during the follow up period (dark line; stage III, dotted line; stage IV). Recurrence-free subjects Stage III Stage IV

4 Na Young Sung, et al. Prognosis of endometriosis after surgical treatment in adolescents below 20 year age Table 3. Analysis of clinical characteristics associated with recurrence of endometriomas after the fi rst line surgery No recurrence after the operation Recurrence after the operation P-value Age 18.5 ± ± Body mass index 20.8 ± ± Largest cyst size at operation 7.4 ± ± Follow-up months 18.5 ± ± a Menarche 13.1 ± ± Nature of the cysts (total 55 cases) Unilateral Bilateral 7 4 r-afs Stage 0.01 b I 15 0 II 6 0 III 28 5 IV 18 7 Post op medication 0.53 N 31 4 Y 36 8 Data are presented as mean±standard deviation. rafs, revised American Fertility Society. P=0.005, likelihood ratio for trend. b P<0.05. Table 4. Associated Müllerian anomalies in patients with endometriosis Age Menarche Diagnosis Operation Double uterus with hematocolpus Left hemihysterectromy with left slapingo-oophorectomy Double uterus with hydrosalpix Laparoscopic left hemihysterctomy Double uterus with endometrioma Left hemihysterectromy enucleation of leftt ovarian cyst Double uterus (transverse vaginal septum) with endometrioma Septotomy with laparoscopic left ovarian cyst enucleation Double uterus (transverse vaginal septum) with endometrioma Laparoscopic right ovarian cyst enucleation Double uterus (transverse vaginal septum) with hematocolpas Diagnostic laparoscopy with septotomy 자궁내막증은 18세이전이라하더라도지속되는생리통이있으면서 NSAID나경구용피임제에반응하지않는경우에생각해봐야한다. 이렇게지속적인통증을호소하는경우에는진단복강경또는수술적복강경을고려해봐야하지만반드시통증에대한평가를 3-6개월이상한후에고려하는것을권고한다 [14]. 본연구는수술로서자궁내막증이확진된환자들을후향적으로연구하였기때문에실제로수술을받은청소년들이얼마나통증에대한치료를받았는지를알기에는제한이있다. 그렇지만병원내원당시의주증상이생리통, 골반통및위장관계통증등통증과관련된증상이약 79% 인것으로미루어보아서는통증이심한경우에는자궁내막증의동반가능성을염두에두어야할것으로보인다. 수술전증상은전형적인자궁내막증을보이는경우는약절반으로그외에는비특이적인소견으로내원하는경우도많았다. 자궁내막증진단시건강과관련된삶의질 (health-related quality of life) 에대한문제도고려해보는것이바람직하다. 자궁내막증을가지고있는청소년은우울증, 공포감, 불안함등을가지고있을수있으며, 학교생활등과같은일상생활에지장을초래할수있다 [9]. 전체청소년의약 60% 에서는생리통을호소하고있으며이중약 14% 에서는잦은결석을보고할정도로일상생활에지장을주는것으로알려져있다 [15]. 그러나청소년기에자궁내막증으로진단된환자들의건강과관련된삶의질에대한연구는많지않은실정이다. 성인이되어서수술로심부자궁내막증을진단받은환자들의경우과거력을조사한결과학교다닐때생리통으로인한결석률이유의하게높았으며일차성생리통이라고진단받고경구용피임제를복용한빈도가유의하게높은것으로나타났다 [16]. 실제로특정한증상이나타나면서자궁내막증으로수술받기까지의기간은다양하지만약 6-12년이라고알려져있다 [17,18]. 일부에서는청소년기에적절한수술을하는것이통증의완화및만족 451

5 KJOG Vol. 54, No. 8, 2011 도가높다고도한다 [19]. 심부자궁내막증의경우증상도심하고, 불임가능성도높고, 수술하기도쉽지않은경우가많기때문에청소년기라할지라도통증의정도가심한경우에는적절한치료가필요할것으로생각되지만아직까지자궁내막증의조기발견및조기치료가질병의경과에어떠한영향을미치는지는알수없다. 본연구에서는자궁내막증의병기별로재발률을관찰하였는데경증의자궁내막증환자에서추적관찰기간동안유의한재발은없었다. 다만병기 III, IV기의환자인경우는그재발률이유의하게높은것을알수있었다. 그렇기때문에수술결과청소년기에진행된병기로진단받은경우에는환자들에게지속적인교육및재발방지를위한적절한약물치료의병합이필요할것으로보인다. 청소년기의자궁내막증은수술적치료뿐만아니라통증에대한치료를지속적으로병행해야하는데여기에가장많이쓰이는약물은경구용피임약, GnRH agonist과비스테로이드계진통제이다 [4]. 본연구에서는약 55.7% 에서는수술후약물치료를시행하였으나특별한약물치료없이경과를관찰한예가상당수를차지하였다. 이는이전에 Cho 등 [11] 의국내연구결과보다높게나타났는데향후에는청소년기일수록수술후적극적인약물치료의병행이있어야할것으로보인다. GnRH agonist의경우에는골소실을가져올수있기때문에보통 16세이전에서는사용하지않는것을권고한다 [4]. 16세이상의청소년기에서는 GnRH agonist를사용해볼수있으며이경우에는보완치료 (add-back therapy) 를같이시행하는것이혈관운동증상 (vasomotor symptom) 과골밀도의변화를최소화시킬수있다고이미알려져있다. 일반적으로경구용피임약이가장안전하며순응도가높은것으로알려져있으며 10년이상장기간복용을해도사망률이나기타질병이환율이증가하지는않는것으로알려져있다 [20]. 본연구에서재발한군과재발하지않은군을비교하였을때병기가높을수록재발률이높아짐을알수있었다. 재발한군의추적관찰기간이유의하게높았는데이는자궁내막증이시간이지남에따라재발률이증가하는것을간접적으로반영해주는결과라고볼수있겠다. 환자들이재발되지않고추적관찰기간을지내는양상 (recurrence free survival) 도비슷한결과를보여주었는데시간이지날수록그빈도가높아짐을알수있었다. 자궁내막증은수술후약물치료를적절하게병행함으로써재발률을낮출수있는것으로알려져있으나앞서언급한것처럼약물치료의빈도자체가높지않고환자수가적어서본연구에서는정확한상관관계를분석하기어려운것으로보인다. 청소년기에진단된자궁내막증의경우임신을할때까지상당히오랜기간이걸릴수있는데아직까지는청소년기에진단된자궁내막증환자의재발률이나임신율에대해서는많이알려져있지않기때문에추적관찰기간동안의재발및재치료의효용성에대한연구가더있어야한다. 본연구는후향적연구이기때문에재발에관련된요인을제대로분석하지못하였다는제한점이있으며, 재발의정의를초음파의소견에의존하였기때문에수술후통증에대한평가및재발여부에대한고찰도부족하다고본다. 향후좀더정확한연구를위하여서는자궁내막증으로진단된환자들의대규모전향적인코흐트연구가필요할것으로생각되며, 삶의질, 통증에대한치료, 정신적불안에대한치료또한병행되어야할것으로생각된다. References 1. Goldman MB, Cramer DW. The epidemiology of endometriosis. Prog Clin Biol Res 1990;323: American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 310, April Endometriosis in adolescents. Obstet Gynecol 2005;105: Schroeder B, Sanfi lippo JS. Dysmenorrhea and pelvic pain in adolescents. Pediatr Clin North Am 1999;46: Laufer MR, Goitein L, Bush M, Cramer DW, Emans SJ. Prevalence of endometriosis in adolescent girls with chronic pelvic pain not responding to conventional therapy. J Pediatr Adolesc Gynecol 1997;10: Reese KA, Reddy S, Rock JA. Endometriosis in an adolescent population: the Emory experience. J Pediatr Adolesc Gynecol 1996;9: Vercellini P, Fedele L, Arcaini L, Bianchi S, Rognoni MT, Candiani GB. Laparoscopy in the diagnosis of chronic pelvic pain in adolescent women. J Reprod Med 1989;34: Schifrin BS, Erez S, Moore JG. Teen-age endometriosis. Am J Obstet Gynecol 1973;116: Goldstein DP, decholnoky C, Leventhal JM, Emans SJ. New insights into the old problem of chronic pelvic pain. J Pediatr Surg 1979;14: Gao X, Yeh YC, Outley J, Simon J, Botteman M, Spalding J. Health-related quality of life burden of women with endometriosis: a literature review. Curr Med Res Opin 2006;22: Goldstein DP, De Cholnoky C, Emans SJ. Adolescent endometriosis. J Adolesc Health Care 1980;1: Cho HJ, Bai SW, Kim JY, Lee KJ, Cho DJ, Song CH, et al. Study on endometriosis in an adolescent population. Korean J Obstet Gynecol 2001;44: Revised American Society for Reproductive Medicine classifi - cation of endometriosis: Fertil Steril 1997;67: Mais V, Guerriero S, Ajossa S, Angiolucci M, Paoletti AM, Melis GB. The effi ciency of transvaginal ultrasonography in the diagnosis of endometrioma. Fertil Steril 1993;60: Laufer MR, Sanfi lippo J, Rose G. Adolescent endometriosis: diagnosis and treatment approaches. J Pediatr Adolesc Gynecol 2003;16:S

6 Na Young Sung, et al. Prognosis of endometriosis after surgical treatment in adolescents below 20 year age 15. Klein JR, Litt IF. Epidemiology of adolescent dysmenorrhea. Pediatrics 1981;68: Chapron C, Lafay-Pillet MC, Monceau E, Borghese B, Ngô C, Souza C, et al. Questioning patients about their adolescent history can identify markers associated with deep infi ltrating endometriosis. Fertil Steril 2011;95: Ballard K, Lowton K, Wright J. What s the delay? A qualitative study of women s experiences of reaching a diagnosis of endometriosis. Fertil Steril 2006;86: Hadfi eld R, Mardon H, Barlow D, Kennedy S. Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK. Hum Reprod 1996;11: Stavroulis AI, Saridogan E, Creighton SM, Cutner AS. Laparoscopic treatment of endometriosis in teenagers. Eur J Obstet Gynecol Reprod Biol 2006;125: Colditz GA. Oral contraceptive use and mortality during 12 years of follow-up: the Nurses Health Study. Ann Intern Med 1994;120: 세이하청소년기여성의자궁내막증의수술적치료후예후 관동대학교의과대학제일병원산부인과성나영, 김봉석, 조연진, 추연실, 김주명, 양승헌 목적자궁내막증으로수술적치료를한환자중 20세이하환자의임상양상, 중증도및재발률에대해알아보고자한다. 연구방법본연구는 2000년 1월부터 2010년 10월까지제일병원산부인과에서수술후자궁내막증으로진단받은환자중에서 20세미만환자 79 명을대상으로후향적연구를시행하였고, 수술결과및임상증상을검토하였다. 결과수술받은환자의평균나이는 18.5세이며, 15세이하의나이에수술받은환자는 5명으로 6.3% 를차지하였다. 뮐러리안관기형과관련된경우는총 6예로 7.6% 를차지하였다. 환자의약 79% 에서생리통, 비주기성골반통또는위장관계통의통증과같은통증관련된증상이있었다. 자궁내막증은환자들의평균추적관찰기간동안 (33.7±28.5개월) 20.3% 에서병기 I기에, 7.6% 가병기 II기에, 40.5% 가병기 III기에발견되었다. 병기 I, II기의환자에서는추적관찰기간동안유의한재발은없었다. 병기 III, IV기인경우에는약 15.6% 와 28% 에서재발이있었다. 추적관찰결과 36개월에 82.5% 에서질병의재발을보이지않았다. 다만환자들의추적관찰기간이길어질수록재발의빈도는점점높아짐을알수있었다. 결론자궁내막증은청소년및 20대초반연령에서발생할수있으며, 그재발률은진행된병기에서더높다. 자궁내막증은진행성질환이므로조기에진단을하여적절한치료가필요할것으로생각된다. 중심단어 : 자궁내막증, 청소년기, 재발, 뮐러리안관기형 453

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical