ORIGINAL ARTICLE Korean J Obstet Gynecol 2012;55(6):371-377 http://dx.doi.org/10.5468/kjog.2012.55.6.371 pissn 2233-5188 eissn 2233-5196 QUALITY OF LIFE ACCORDING TO ADD-BACK THERAPY DURING GNRH AGONIST TREATMENT IN ENDOMETRIOSIS PATIENTS Jong Kil Joo, MD, In Kook Jung, MD, Ki Hyung Kim, MD, Kyu Sup Lee, MD Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Korea Objective This study was performed to investigate the effect of add-back therapy on quality of life during postoperative gonadotropin-releasing hormone (GnRH) agonist therapy for endometriosis. Methods Fifty-one patients who were diagnosed as stage III/IV endometriosis after laparoscopic ovarian cystectomy from January 2009 to December 2010 were divided into GnRH agonist with add-back therapy group and GnRH agonist only group. Add-back therapy was started before third injection of GnRH agonist. Short form health survey (SF-36) instrument was checked preoperatively, at the time of 6th GnRH agonist therapy and 6 months after GnRH agonist therapy. Results There were no differences between two groups on the mean age, body mass index and revised American Fertility Society score. In most cases, add-back therapy was added because of menopausal symptoms. Pelvic pain and dysmenorrhea showed no differences between two groups on each survey period. At the time of 6th GnRH agonist therapy, physical function in add-back therapy group was improved significantly compared with preoperative period (85.7±8.8 vs. 91.0±10.4, P=0.011). In GnRH only group, physical function at preoperative period was rather higher than at the time of 6th GnRH agonist therapy. Conclusion Add-back therapy during postoperative GnRH agonist therapy showed no negative effect on pelvic pain and dysmenorrhea. Physical function was improved in add back group. Add-back therapy might have an influence on quality of life in patients receiving postoperative GnRH agonist therapy for endometriosis. Keywords: Endometriosis; Add-back; Quality of life 자궁내막증은가임기여성에서가장흔한부인과질환의하나로, 골반통, 생리통을야기하며불임증의주요한원인으로알려져있다 [1]. 치료는통증의정도, 자궁내막종의크기, 임신을원하는가등의임상적상황에따라다양한방법이제시되고있으나, 현재까지일반적으로받아들여지고있는원칙은복강경수술을통한자궁내막증병변의조직학적확인과수술이후에재발방지를위한약물치료이다. 재발방지를위한치료는다양한호르몬제제를통해낮은혈중에스트로겐농도를획득하게하는것이다. 이를위해현재가장많이사용되고있는제제는성선자극호르몬분비호르몬효능제 (gonadotropin-releasing hormone, GnRH agonist) 이다 [2]. GnRH agonist는뇌하수체 GnRH 수용체의하향조절을통해성선자 Received: 2012.1.13. Revised: 2012.3.15. Accepted: 2012.5.3. Corresponding author: Ki Hyung Kim, MD Department of Obstetrics and Gynecology, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 602-739, Korea Tel: +82-51-240-7287 Fax: +82-51-248-2384 E-mail: ghkim@pusan.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 371
KJOG Vol. 55, No. 6, 2012 극호르몬의분비를억제하며이를통해난소에서에스트로겐의합성이감소하게된다 [3,4]. 그러나 GnRH agonist의사용은저에스트로겐혈증에따른부작용, 즉, 안면홍조, 질위축등의폐경기증상과골소실의발생에따라그사용이제한적이다. 이에저에스트로겐혈증의부작용을해소하기위해저용량의에스트로겐 / 프로제스테론복합제의사용이제안되었는데, 이는자궁내막증의재발은예방하면서도저에스트로겐혈증의부작용은해소할수있는혈중에스트로겐농도를유지하고자하는방법이다 [5,6]. 많은연구를통해 GnRH agonist 사용시에호르몬보충요법을통해골밀도의감소를어느정도예방할수있음이밝혀졌고, 폐경증상도완화됨이밝혀졌다 [7]. 그러나호르몬보충요법에따라실제로삶의질적측면에어떠한영향이있는지는밝혀진바가많지않다. 이에본연구에서는수술적처치로 III/IV기의자궁내막증을진단받고 6회의 GnRH agonist를투여받은환자를대상으로수술전, 후에설문지를통해호르몬보충요법의시행에따른삶의질변화양상을살펴보고자하였다. 2009년 1월부터 2010년 12월까지부산대학교병원을방문하여복강경수술을통해난소낭종절제술을시행받고 III/IV기의자궁내막증으로진단받은 60명중설문지에성실히응답하고 6회의 GnRH agonist 투여후, 6개월까지외래를통해추적관찰이가능했던 51명을대상으로하였다. 본연구에서는 GnRH agonist와함께호르몬보충요법을시행받은환자는 24명이었으며, GnRH agonist 만단독으로투여받은환자는 27명이었다. 각각의평균연령, 체질량지수, 병기는 Table 1과같다. 수술은복강경하에서난소낭종절제술이시행되었고, revised American Fertility Society score (rafs) 에따라병기가결정되었다. GnRH agonist는 goserelin depot (Zoladex, Zeneca Ltd., London, UK) 3.6 mg을수술후조직학적으로자궁내막증이진단된경우외래첫방 문시투여하였으며, 이후 4주간격으로 6회까지투여하였다. 호르몬보충을시행한군은 GnRH agonist 2차례주사후월경이완전히없어진것을환자스스로가확인하고받아들일수있도록 3회의 GnRH agonist를투여받기위해병원을내원하였을때, 담당의사와의상담이후시작하였다. 사용된제제는티볼론 (Livial, NV Organon, Oss, Netherlands) 2.5 mg 또는 drospirenone (DRSP) 2 mg/estradiol-17ß (E2) 1 mg (Angeliq, Schering AG, Berlin, Germany) 였다. 담당의사와의상담은모든환자에서 1명의전문의에의해이루어졌으며, 호르몬보충요법에따른폐경증상의완화, 골소실의감소등의이득에대해충분한설명후에환자의결정에따라시행유무를결정하였다. 건강수준을확인하기위한설문조사는삶의질적평가에널리이용되는 short form health survey (SF-36) instrument [8,9] 의한국어번역본으로시행하였으며, 3차에걸쳐시행되었다. SF-36은그점수가높을수록향상된건강수준을나타내는것으로설문지는환자본인이직접작성하여제출하였으며, 1차설문조사는수술전외래방문시또는수술을위해입원한날에시행하였고, 2차는 6번째 GnRH agonist 투여를위해병원을방문하였을때시행하였다. 3차설문조사는 6회의 GnRH agonist 투여가끝난 6개월후에추적, 관찰을위해외래를방문하였을때시행하였다. 1차, 3차설문조사시에골반통과생리통의정도를시각통증척도 (visual analogue scale) 를통해조사하였으며, 2차설문조사시에는호르몬보충요법을시행한또는시행하지않은이유등에대해추가적인설문을시행하였다. 모든자료는평균과표준편차로표시하였다. 환자군간의연령, 체질량지수, 병기, rafs score, 생리통등은 Student t-test를통해평균을비교하였고, 건강수준에대한설문에대해서는 Mann-Whitney U test 와 Wilcox signed-rank test를통해통계분석을시행하였다. 모든통계분석은 SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA) 프로그램을통해시행하였다. Table 1. Basic characteristics of patients Add-back group (n = 24) No add-back group (n = 27) P-value Age (yr) 31.9 ± 2.0 33.0 ± 3.2 0.161 Body mass index (kg/m²) 22.2 ± 2.3 22.8 ± 3.8 0.484 Stage 0.594 III 9 11 IV 15 16 Revised American Fertility Society score 45.4 ± 14.7 45.2 ± 21.0 0.971 Values are presented as mean ± standard deviation or number of patients. 372 WWW.KJOG.ORG
Jong Kil Joo, et al. Add-back therapy in endometriosis 조사대상에포함된 51명중호르몬보충요법을시행받은군은 24명이었으며, 호르몬보충요법없이 GnRH agonist만투여받은군은 27명이었다. 각군의평균연령은 31.9 ± 2.0, 33.0 ± 3.2세로통계적인차이는없었으며, 체질량지수도통계적차이는없었다. 병기는보충요법군에서 III기 9명, IV기 15명이었고, 보충요법미시행군은 11명, 16명이었다. rafs score는각각 45.4 ± 14.7, 45.2 ± 21.0로역시두군간에통계적인차이는없었다 (Table 1). 호르몬보충요법에사용된약제는티볼론이 13명, DRSP/E2가 11명이었다. 보충요법을시행한이유는중복이가능하도록조사하였을때폐경증상의완화를위한경우가 24명, 골소실의감소를위한경우가 Table 2. Drugs and causes of add-back therapy Add-back group (n=24) No. (%) Drugs for add-back Tibolone 13 (54.2) Angeliq 11 (45.8) Causes of add-back Menopausal symptoms a 24 (100) Hot fl ush 19 (79.2) Emotional change 18 (75.0) Night sweat 14 (58.3) General ache 14 (58.3) Vaginal dryness 11 (45.8) Insomnia 6 (25.0) Prevention of bone loss 4 (16.7) a Multiple causes included. 4명으로조사되었다. 약물에의해유도된주된급성기폐경증상은안면홍조가 19명, 감정변화가 18명, 야간발한이 14명, 전신통증이 14명, 질건조감이 11명, 불면증이 6명으로조사되었다 (Table 2). 보충요법미시행군에서는증상을참을만하기때문에시행하지않겠다는환자가 24명, 2가지호르몬사용으로인한불안감이 2명, 약물효과상쇄에대한염려가 4명, 유방질환발생에대한염려가 4명, 다른약물복용시경험했던위장장애로인한약물기피가 4명이었다 (Fig. 1). 호르몬보충요법에따른통증에미치는부정적인영향을조사하기위해모든환자를대상으로수술전, 6회의 GnRH agonist 투여시, 최종투여 6개월후에골반통과생리통의정도를시각통증척도를통해조사한결과는 Table 3과같다. 골반통과생리통모두양군에서수술전에 4.8 ±1.5, 4.7 ±1.5로높았으나, 진단후 GnRH agonist 투여시나 6개월후추적관찰기간에는통증의감소를보였고, 이는통계적인유의성을보였다. 그러나호르몬보충요법유무에따라전조사기간에걸쳐두군간에통증의정도에차이는없었다. SF-36을이용한건강수준의비교는 Table 4와같다. Table 4는각군에서수술전과 6회의 GnRH agonist 투여시, 수술전과 GnRH agonist 투여종료 6개월후, 두군간에는대칭되는시기, 즉, 수술전시기, 6회의 GnRH agonist 투여시, 투여종료 6개월후에대해통계적분석을시행하였으며, 통계적유의성이있는경우만을표시하였다. 격렬한활동이나걷기등의신체기능 (physical function) 은호르몬보충요법군에서는수술전에비해 GnRH agonist 6회투여시에오히려향상된결과를보였다 (85.7 ± 8.8 vs. 91.0 ±10.4, P = 0.011). 하지만비보충요법군에서는 GnRH agonist 6회투여시수술전보다낮은수치를보였다 (87.6 ± 7.1 vs. 82.6 ± 4.0, P = 0.002). GnRH agonist 6회투여시에양군을비교해보면보충요법군에서비보충요법군에비해통계적으로유의하게높은결과를보였다 (91.0 ± 10.4 vs. 82.6 ± 4.0, P = 0.027). 사회적기능 (social function) 에서는수술전점수가보충 Table 3. Effects of add-back therapy on pelvic pain and dysmenorrhea Add-back group No add-back group P-value Pelvic pain Preoperative 4.8 ± 1.5 (A) 4.7 ± 1.4 (a) 0.756 At 6th gonadotropin-releasing hormone agonist injection 1.5 ± 0.9 (B) 1.4 ± 0.8 (b) 0.830 6 months later 1.7 ± 1.1 (C) 1.6 ± 1.0 (c) 0.786 Dysmenorrhea Preoperative 4.6 ± 1.6 (D) 4.3 ± 1.4 (d) 0.522 6 months later 2.1 ± 1.0 (E) 2.0 ± 1.2 (e) 0.893 Values are presented as mean ± standard deviation. Pelvic pain and dysmenorrhea values are expressed in visual analogue scale units. P<0.001, between (A) and (B), (A) and (C), (D) and (E), (a) and (b), (a) and (c), (d) and (e); P=0.447, between (B) and (C); P=0.476, between (b) and (c). WWW.KJOG.ORG 373
KJOG Vol. 55, No. 6, 2012 Gastrointestinal discomfort Fear for breast disease Reversal of drug effects Fear for 2 hormones Tolerable symptoms Fig. 1. Causes of no add-back therapy a (n = 27). a Multiple causes included. Table 4. Differences in the patients quality of life, as assessed by SF-36, before and after treatment Preop. (A) Add-back group At 6th GnRHa (B) 6 mo F/U Preop. (C) No add-back group At 6th GnRHa (D) 6 mo F/U P-value Physical function 85.7 ± 8.8 91.0 ± 10.4 87.7 ± 16.8 87.6 ± 7.1 82.6 ± 4.0 89.3 ± 6.9 0.011 a 0.251 b 0.027 c 0.002 d Role physical 70.8 ± 21.5 81.3 ± 25.5 70.8 ± 27.5 78.6 ± 25.2 76.8 ± 28.0 75.0 ± 29.4 NS Role emotional 79.2 ± 21.5 87.5 ± 16.4 81.9 ± 24.7 79.8 ± 22.8 78.6 ± 31.7 79.0 ± 26.4 NS Vitality 57.9 ± 20.4 62.3 ± 19.9 57.3 ± 21.5 58.8 ± 14.1 59.1 ± 16.5 57.8 ± 15.5 NS Mental health 62.0 ± 17.0 66.8 ± 15.3 62.1 ± 21.4 67.4 ± 8.8 63.7 ± 13.3 64.1 ± 12.3 NS Social function 79.7 ± 26.0 81.3 ± 24.7 80.2 ± 22.4 78.1 ± 11.1 79.5 ± 25.0 76.9 ± 21.6 0.039 b Body pain 71.5 ± 10.1 78.5 ± 17.9 74.6 ± 18.3 71.4 ± 15.4 79.1 ± 20.8 72.6 ± 19.0 0.033 d General health 55.8 ± 17.2 57.7 ± 16.1 54.6 ± 16.0 57.1 ± 19.1 55.9 ± 17.6 56.3 ± 18.5 NS Values are presented as mean ± standard deviation. SF-36, short form health survey; Preop., preoperative; At 6th GnRHa, at the time of 6th gonadotropin-releasing hormone agonist injection; 6 mo. F/U, 6 months after completion of GnRH agonist; NS, not signifi cant. a (A) vs. (B), b (A) vs. (C), c (B) vs. D, d (C) vs. (D). 요법군에서유의하게높아 (79.7 ± 26.0 vs. 78.1 ± 11.1, P = 0.039), 이후의양군간의비교는한계가있을것으로생각된다. 신체통증 (body pain) 에서는비보충요법군에서수술전이 6회 GnRH agonist 투여시보다통계적으로유의하게높은수치를보였다 (71.4 ± 15.4 vs. 79.1 ± 20.8, P = 0.033). 양군에서 GnRH agonist 투여가종료되고 6 개월후에시행한설문조사에서는모든항목에있어통계적차이를보이지않았다. 그외신체역할, 감정역할, 활력도, 정신건강, 전신건강상태영역에서는모두통계적인유의성을보이지않았다. 자궁내막증에대한보존적수술이후에 GnRH agonist의사용은자궁내막증의재발을방지하고통증을경감시키는데매우효과적인것으로알려져있고, 현재자궁내막증에대한표준적인치료로받아들여지고있다 [10,11]. 그러나 GnRH agonist는저에스트로겐혈증에따르는폐경증상이나골소실등을유발하게되며, 이는장기간의투여에제약을가져왔다. 이에따라부작용을최소화하고환자의순응도를높이고 374 WWW.KJOG.ORG
Jong Kil Joo, et al. Add-back therapy in endometriosis 자다양한호르몬제를함께사용하는보충요법이제안되었다 [12]. 호르몬보충요법의장점에대해서는그동안많은발표들이있었으나, 실제로호르몬보충요법이얼마나폭넓게사용되고있는가에대해서는자료가많지않다. 미국의환자청구자료를바탕으로한 2010년의보고에따르면자궁내막증환자에서호르몬보충요법은 32.0% 에서시행되는것으로알려져있다 [13,14]. 이는알려진호르몬보충요법의장점들을고려할때, 비교적낮은것으로생각된다. 본연구에서는담당의사와의상담후에호르몬보충요법의시행을환자스스로결정하게하였을때, 47.1% 에서호르몬보충요법을시행하기를원하였다. 이러한결과는호르몬보충요법의장, 단점에대한충분한설명이순응도를높이는데가장중요한요소임을시사한다고여겨진다. 본연구에서호르몬보충요법을꺼리는이유는다양하였는데, 증상을참을만하기때문에시행하지않겠다는환자가 88.9% 로가장많았다. 하지만이들도대부분이폐경증상을호소하며불편해하였으나다른이유를중복해서가지고있었으며, 호르몬제를복용하지않고참아보겠다는의지로복용을꺼리는경우들이었다. 또한 2가지호르몬제를같이사용한다는것에대한불안감, 한약제는에스트로겐을감소시키고보충요법제는에스트로겐을올려주어약물효과가상쇄되지않을까하는염려를가지고있었다. 이처럼호르몬제에대해서는많은여성들에서여러가지염려와선입견이있음을시사하고있다 (Fig. 1). 골반통과생리통에대해서수술전과 GnRH agonist 사용중, 6개월후에시행한설문조사에서수술전에비해통증이유의하게감소하였으며, 이러한통증의감소는호르몬보충요법유무에따라차이를보이지않았다. 이러한결과는호르몬보충요법이수술후 GnRH agonist 사용시기에통증을증가시키지않으며, 6개월의추적, 관찰동안재발과무관함을시사한다고하겠다. 그러나본연구는 6개월의짧은기간동안시행되었기에재발과무관하다고결론내리기에는다소무리가있다. SF-36 설문지를통해건강수준을조사한결과에서는신체기능 (physical function) 에서수술전보다수술후 GnRH agonist 투여중일때에호르몬보충요법시행군에서비시행군에비해통계적으로높게조사되었다. SF-36 설문지의신체기능에포함되는항목으로는격렬한활동 ( 달리기, 무거운물건들기 ), 중등도의활동 ( 식탁혹은밥상옮기기, 진공청소기밀기 ), 음식물 ( 잡화류 ) 들기혹은옮기기, 5-6 계단올라가기, 상체굽히기, 무릎굽히기, 1마일 (1.6 km) 이상걷기, 몇구역 (several block) 걷기, 스스로목욕하기혹은옷입기등이포함된다. 호르몬보충요법을시행하지않은군에서는수술전에비해 GnRH agonist 사용중에통계적으로유의하게낮게조사되었다. 이러한결과는호르몬보충요법이신체기능의향상에유용함을보여준다고하겠다. 그러나그외의영역에서는호르몬보충요법에따른통계적차이를확인할수없었다. 유사한보고로 Zupi 등 [15] 은자궁내막증이재발한환자군을대상으로 GnRH agonist 단독, GnRH agonist와호르몬보충요법, estroprogestin을사용한군에서 GnRH agonist와호르몬보충요법군에서 SF-36을이용한조사결과에서다른군에비해전반적인건강상태 (general health), 활력도 (vitality), 신체기능 (physical function) 등 에서더나은결과를보여호르몬보충요법이삶의질을향상시키는데효과적임을제시하고있다. 호르몬보충요법은삶의질뿐만아니라 GnRH agonist를사용하는과정에서환자의순응도를증가시키는데도효과적인것으로보고되었다 [13]. Fuldeore 등 [13] 의보고에의하면호르몬보충요법을시행받지않는군에서 3회의 GnRH agonist 사용후에치료를중단하는비율이 1.6배높은것으로조사되었다. 연령에따라서는젊은연령군에서호르몬보충요법의순응도가더높으며고령에서는낮은것으로조사되었다. 이와같이호르몬보충요법은앞서제시한삶의질증진뿐만아니라치료적 GnRH agonist 사용에있어서도순응도를높일수있음을알수있다. 본연구에서는호르몬보충요법으로티볼론과 DRSP/E2가사용되었으나 FDA에공인을받은약제는 norethindrone acetate가유일하다 [16]. Norethindrone acetate는에스트로겐활성을가지는프로제스틴으로서에스트로겐활성을가지는대사산물을통해호르몬보충요법에사용되는것으로알려져있다. 그러나 norethindrone acetate 외에티볼론이나 estrogen-progestin 복합제역시효과적인것으로알려져있다 [17,18]. 최근에는단기간저용량의에스트로겐단독요법도효과적으로저에스트로겐혈증의증상을관리할수있다는보고가있어 [17], 호르몬보충요법은다양한제제를통해환자의상황에맞추어유용하게사용할수있을것이다. 호르몬보충요법의시작시기에대해서본연구에서는 3회의 GnRH agonist 투여를위해방문시에시작되었는데, 이는주사후월경이소실되어진것을환자스스로가확인하고받아들일수있는시점이면서저에스트로겐혈증증상이발현한후에상담을시행함으로써증상의정도를고려해서환자가스스로가호르몬보충요법의시행유무를판단하도록하기위해서였으며, 저에스트로겐혈증의증상발현은이후에호르몬보충요법의순응도향상에도도움을줄것으로생각되었기때문이다. 그러나문헌에따르면대부분의호르몬보충요법이 GnRH agonist의사용과동시에시행되는것으로보고되고있으며 [3,4], 시작시기를미루는것이자궁내막증치료에유용하다거나어떠한해로운결과를가져온다는보고는없다 [19]. 오히려골소실의측면에서는즉각적인호르몬보충요법이좀더유용하다는보고가있다. Al-Azemi 등 [20] 은만성골반통을가진환자에서 18개월의 GnRH agonist 치료군을대상으로즉각적인호르몬보충요법을시행한군과 6개월후에시작한군에서즉각적인호르몬보충요법을시행한군이통계적으로유의하게골밀도의감소가적음을보고하였다. 본연구에서는수술과이후의 GnRH agonist의사용으로자궁내막증에의한통증이감소됨을확인하였고, 이과정에서호르몬보충요법을시행하더라도골반통이나생리통에는부정적인영향이없으며, 일부에서신체기능을향상시키는영향도관찰하였다. 그러나본연구에는몇가지제한점이있는데우선, 대상군의수에있어 SF-36을사용한연구를기초로그수를결정하였으나, SF-36의평가항목이다수이고, 각항목에따라대상군의수가다르게결정될수있으며, 외국의문헌과비교하여 Table 4에제시된각각의수치가높고편차가큰경향이 WWW.KJOG.ORG 375
KJOG Vol. 55, No. 6, 2012 있어, 설문조사대상군의수가적어결과분석에영향을미쳤을가능성이있다. 또한의사와의상담이후에호르몬보충요법의시행유무를결정하였고약제의선택에있어서도두가지약제를사용하였으므로편견 (bias) 이개입되었을가능성이있다. 또한 GnRH agonist를투여중이면서, 보충요법은아직시행하기전인시기에설문조사가추가로시행되어분석되었다면좀더명확히보충요법의효과를확인할수있었을것으로생각된다. 이와같은제한점에도불구하고본연구는자궁내막증수술이후에 GnRH agonist 사용시기에호르몬보충요법을시행함으로써이미잘알려진골소실방지뿐만아니라신체기능에도향상을확인하였으며, 이를통해자궁내막증의장기적인치료와관리를위한약물의사용에있어참고자료로이용하여환자와의상담에도움을줄수있을것으로생각된다. 향후에좀더체계적인연구를통해다양한약제와연령군에서호르몬보충요법의효과와건강수준에미치는영향을연구하는것이필요할것으로생각된다. 본연구는보건복지가족부보건의료기술진흥사업의지원에의하여이루어진것임 ( 과제고유번호 : A084711). References 1. Olive DL, Schwartz LB. Endometriosis. N Engl J Med 1993;328:1759-69. 2. Park HM, Lee WS, Song MS, Hur M. The effect of progesterone add-back therapy on skeletal status during GnRH agonist therapy for endometriosis. Korean J Obstet Gynecol 2003;46:288-95. 3. Batzer FR. GnRH analogs: options for endometriosis-associated pain treatment. J Minim Invasive Gynecol 2006;13:539-45. 4. Olive DL. Gonadotropin-releasing hormone agonists for endometriosis. N Engl J Med 2008;359:1136-42. 5. Kiilholma P, Tuimala R, Kivinen S, Korhonen M, Hagman E. Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone versus goserelin combined with estrogen-progestogen add-back therapy in the treatment of endometriosis. Fertil Steril 1995;64:903-8. 6. Fernandez H, Lucas C, Hédon B, Meyer JL, Mayenga JM, Roux C. One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial. Hum Reprod 2004;19:1465-71. 7. Friedman AJ, Hornstein MD. Gonadotropin-releasing hormone agonist plus estrogen-progestin add-back therapy for endometriosis-related pelvic pain. Fertil Steril 1993;60:236-41. 8. McHorney CA, Ware JE Jr, Raczek AE. The MOS 36-Item Short- Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993;31:247-63. 9. Jenkinson C, Coulter A, Wright L. Short form 36 (SF36) health survey questionnaire: normative data for adults of working age. BMJ 1993;306:1437-40. 10. Valle RF, Sciarra JJ. Endometriosis: treatment strategies. Ann N Y Acad Sci 2003;997:229-39. 11. Jee BC, Lee JY, Suh CS, Kim SH, Choi YM, Moon SY. Impact of GnRH agonist treatment on recurrence of ovarian endometriomas after conservative laparoscopic surgery. Fertil Steril 2009;91:40-5. 12. Barbieri RL. Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 1992;166:740-5. 13. Fuldeore MJ, Marx SE, Chwalisz K, Smeeding JE, Brook RA. Add-back therapy use and its impact on LA persistence in patients with endometriosis. Curr Med Res Opin 2010;26:729-36. 14. Olive DL. The role of add-back therapy in the United States. Drugs Today (Barc) 2005;41 Suppl A:23-6. 15. Zupi E, Marconi D, Sbracia M, Zullo F, De Vivo B, Exacustos C, et al. Add-back therapy in the treatment of endometriosisassociated pain. Fertil Steril 2004;82:1303-8. 16. Surrey ES. Add-back therapy and gonadotropin-releasing hormone agonists in the treatment of patients with endometriosis: can a consensus be reached? Add-Back Consensus Working Group. Fertil Steril 1999;71:420-4. 17. Kim NY, Ryoo U, Lee DY, Kim MJ, Yoon BK, Choi D. The efficacy and tolerability of short-term low-dose estrogen-only add-back therapy during post-operative GnRH agonist treatment for endometriosis. Eur J Obstet Gynecol Reprod Biol 2011;154:85-9. 18. Morris EP, Rymer J, Robinson J, Fogelman I. Effi cacy of tibolone as add-back therapy in conjunction with a gonadotropinreleasing hormone analogue in the treatment of uterine fibroids. Fertil Steril 2008;89:421-8. 19. Surrey ES. Gonadotropin-releasing hormone agonist and addback therapy: what do the data show? Curr Opin Obstet Gynecol 2010;22:283-8. 20. Al-Azemi M, Jones G, Sirkeci F, Walters S, Houdmont M, Ledger W. Immediate and delayed add-back hormonal replacement therapy during ultra long GnRH agonist treatment of chronic 376 WWW.KJOG.ORG
Jong Kil Joo, et al. Add-back therapy in endometriosis cyclical pelvic pain. BJOG 2009;116:1646-56. 자궁내막증여성에서수술후 GnRH agonist 치료중호르몬보충요법유무에따른삶의질변화 부산대학교의학전문대학원산부인과학교실주종길, 정인국, 김기형, 이규섭 목적수술후성선자극호르몬분비호르몬효능제 (gonadotropin-releasing hormone, GnRH agonist) 를투여받는자궁내막증여성에서호르몬보충요법의유무에따른삶의질의변화를조사하여보고자하였다. 연구방법 2009년 1월부터 2010년 12월까지복강경수술을통해난소낭종절제술을시행받고 III/IV기의자궁내막증으로진단받은환자 51명을대상으로 3회의 GnRH agonist 투여시부터호르몬보충요법을함께시행받은군과 GnRH agonist만단독으로투여받은군으로나누어수술전과 6번째 GnRH agonist 투여시기및 GnRH agonist 투여가끝난 6개월후에각각 short form health survey (SF-36) 과골반통, 생리통의정도를조사하였다. 결과두군간에연령, 체질량지수, 병기, revised American Fertility Society score 등은차이가없었으며, 호르몬보충요법을시행하는이유는대부분폐경증상의발생에의한것이었다. 골반통과생리통은각각의조사시기에두군간에차이를보이지않았다. 신체기능 (physical function) 은호르몬보충요법군에서수술전에비해 GnRH agonist 6회투여시에오히려향상된결과를보였고, 비보충요법군에서는수술전이 GnRH agonist 6회투여시보다높은수치를보였다. GnRH agonist 6회투여시에보충요법군에서비보충요법군에비해통계적으로유의하게높은결과를보였다. 결론수술후 GnRH agonist를투여받는자궁내막증환자에서호르몬보충요법을함께시행한경우통증의감소에부정적인영향이없었으며신체기능이더향상된것으로나타났다. 이는호르몬보충요법이이러한환자군에서삶의질에영향을미칠수있음을시사한다. 중심단어 : 자궁내막증, 호르몬보충, 삶의질 WWW.KJOG.ORG 377