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1 폐경기호르몬대체요법후발생한폐색전증 1 인제대학교의과대학내과학교실, 2 병리학교실김선영 1, 박종혁 1, 이현경 1, 이혁표 1, 이혜경 2, 최수전 1, 염호기 1 Pulmonary Thromboembolism after Post-menopause Hormonal Replacement Therapy Sun Young Kim, M.D. 1, Jong Hyeok Park, M.D. 1, Hyun Kyung Lee, M.D. 1, Hyuk Pyo Lee, M.D. 1, Hye Kyung Lee, M.D. 2, Soo Jeon Choi, M.D. 1, Ho-Kee Yum, M.D. 1 1 Department of Internal Medicine and 2 Pathology, Inje University, Seoul, Korea Hormonal replacement therapy (HRT) has been proven for treatment of postmenopausal symptoms such as hot flushes, night sweats and urologic symptoms. HRT became very popular in the 1990's, when there were several reports showing that it also helped with other menopausal complications such as osteoporosis and cardiovascular disease. Recent studies report that the incidence of breast cancer, endometrial cancer, cerebral infarction, coronary artery diseases, deep vein thrombosis and pulmonary thrombembolism could rise after HRT. mong these side effects of HRT, the risk of pulmonary thromboembolism increases 2 to 4 fold after HRT, but can vary with the use of different doses and preparations. Here, we summarize the risk factors and clinical courses for 5 patients who developed pulmonary thromboembolism after postmenopausal HRT. (Tuberc Respir Dis 2007; 63: ) Key Words: Postmenopause hormone replacement therapy(hrt), Pulmonary thromboembolism, Deep vein thrombosis. 서 폐경후호르몬요법은폐경기의흔한증상으로알려진홍조, 야간발한, 비뇨기계증상등에효과적으로사용되어왔다. 1990년대이러한호르몬요법이폐경기후의골다공증이나심혈관계질환예방에도움이된다는보고는폐경기여성에서호르몬요법의사용을대중화했다. 그러나최근연구에서호르몬요법의부작용으로유방암, 자궁내막암, 뇌졸중, 색전증, 관상동맥질환의빈도가증가된다고알려졌다. 호르몬요법의부작용중폐색전증에대한상대적인위험도는에스트로겐용량및용법등에따라다양하게보고되었다 1,2. 최근연구결과에따르면호르몬요법후심부정맥혈전증, 폐색전증의빈도가 2-4배이상증가된다 년부터 2003년까지폐색전증의위험인자를가지 론 ddress for correspondence: Ho-Kee Yum, M.D. Department of Internal Medicine, Seoul Paik Hospital, Inje University, 85, 2-ga, Jeo-dong, Jung-gu, Seoul , Korea Phone: , Fax: pulho@korea.com Received: ug ccepted: Oct 고있는 5명의폐경기여성을대상으로폐경후호르몬요법이후발생한폐색전증의위험인자와임상경과에대하여요약하였다. 증례증례. 57세여자가왼쪽흉부통증과호흡곤란으로입원하였다. 갑작스런흉통이 5일전부터시작되었으며흡기시심해졌다. 입원 10개월전고혈압진단후 amlodipine 5 mg을복용하였으며, 폐경기증상으로호르몬제 premarin (estrogen conjugated mg) 을복용하였다. 키 165 cm, 체중 80 kg, 신체질량지수 29.3이었다. 혈압은 120/80 mmhg, 맥박수분당 90회, 호흡수분당 20회, 체온은 37.4 였다. 좌하엽에서호흡음이감소되었다. 말초혈액혈색소 12.8 g/dl, 적혈구용적 37%, 백혈구 6,700/mm 3 ( 호중구 54.3%, 림프구 31.9%, 단핵구 6.8%, 호산구 5.9%), 혈소판수 249,000/mm 3 였다. 동맥혈가스검사에서 ph 7.45, PaCO mmhg, PaO mmhg, HCO mmol/l, O 2 saturation 92.8% 였다. 단순흉부 X-선촬영에서왼쪽늑막강의의존성부위에소량의늑막액저류가관찰되었다 (Figure 1). 흉부전산화단층촬 362

Tuberculosis and Respiratory Diseases Vol. 63. No.4, Oct. 2007 Figure 1. Chest X-ray on admission.

Wedge shaped ill-defined inhomogenous density is revealed at minor fissure and pleural surface of right upper lung ().

Multifocal thromboembolism are revealed at mainly segmetal and subsegmental arterial branches supplying both lower lobes ().

(). 영에서양측폐하엽폐동맥에혈전이관찰되었다 (Figure 2). 하지정맥도플러초음파상심부혈전증은보이지않았다. 1년간항응고제 (warfarin) 투약및경과관찰하였으며재발은없었다. 증례. 58세여자가호흡곤란으로입원하였다.

2 Tuberculosis and Respiratory Diseases Vol. 63. No.4, Oct Figure 1. Chest X-ray on admission. Left costophrenic angle obliteration is revealed due to left pleural effusion (). Wedge shaped ill-defined inhomogenous density is revealed at minor fissure and pleural surface of right upper lung (). Figure 2. Computed tomographic angiography. Multifocal thromboembolism are revealed at mainly segmetal and subsegmental arterial branches supplying both lower lobes (). Multifocal thromboembolism are revealed at lobar and segmental branches supplying both whole lungs except right middle lobe (). 영에서양측폐하엽폐동맥에혈전이관찰되었다 (Figure 2). 하지정맥도플러초음파상심부혈전증은보이지않았다. 1년간항응고제 (warfarin) 투약및경과관찰하였으며재발은없었다. 증례. 58세여자가호흡곤란으로입원하였다. 3 일전갑작스런흉부불쾌감이있었다. 이후경도의호흡곤란을느껴오다입원당일호흡곤란이심해져입 원하였다. 환자는 4년전당뇨진단후혈당강하제를복용하였다. 입원 1년 5개월전부터입원 1년전까지개인병원산부인과에서폐경기증상으로 1달에 1번호르몬제 defofemin (estradiol cypionate 5 mg) 과 mirodepo (testosterone cyclopentylprorionate 250 mg) 을근육주사맞았다. 1년전좌하지심부정맥혈전증으로개인병원에서항응고제 (warfarin) 를복용중이었 363

SY Kim et al: Pulmonary thromboembolism after post-menopause hormonal replacement therapy Figure 3. Lower Extrimity Doppler.

Deep vein thrombosis are revealed from left common iliac to common femoral vein (). Table 1.

3 58 testosterone+estradiol 5 DM dyspnea 25.

3 SY Kim et al: Pulmonary thromboembolism after post-menopause hormonal replacement therapy Figure 3. Lower Extrimity Doppler. Deep vein thrombosis are revealed at left popliteal and most proximal superficial femoral vein (). Deep vein thrombosis are revealed from left common iliac to common femoral vein (). Table 1. Summary of the clinical characteristics of subjects Case ge HRT Duration (months) Other risk factor Main symptom MI 57 estrogen conjugated 10 chest pain testosterone+estradiol 5 DM dyspnea 25.9 C 60 estrogen conjugated 34 echet disease, operation D 57 medroxypg+estrogen 68 cruciate ligament injury, operation chest discomfort 22.2 hemoptysis 25.6 E 59 estrogen conjugated 3 long time travel chest pain 23.6 * MI: body mass index; PG: prostaglandin; DM: diabetes mellitus. 다. 키 152 cm, 몸무게 60 kg, 신체질량지수 25.9이었다. 혈압은 140/90 mmhg, 맥박수분당 78회, 호흡수분당 26회, 체온은 36.0 였다. 흉부진찰소견은이상 없었다. 말초혈액혈색소 13.8 g/dl, 적혈구용적 41%, 백혈구 8,150/mm 3 ( 호중구 55.0%, 림프구 34.3%, 단핵구 7.2%, 호산구 2.9%), 혈소판수 364

4 Tuberculosis and Respiratory Diseases Vol. 63. No.4, Oct Table 2. Summary of the radiologic findings of subjects Case Chest CT Lower extremity doppler Subsegmental both lower lobes Multifocal through both lungs No evidence Lt. superficial femoral vein C nterior segment of RUL No evidence D No evidence Lt. common iliac vein E xillary segment of RUL * RUL: right upper lobe. Rt superficial femoral vein 166,000/mm 3 였다. 동맥혈가스검사에서 ph 7.47, PaCO mmhg, PaO mmhg, HCO mmol/l, O 2 saturation 93.7% 였다. 단순흉부 X-선촬영에서양측하엽에관성및낭성기관지확장증이관찰되었다. 흉부전산화단층촬영에서양측페동맥에다발성혈전이관찰되었다 (Figure 2). 하지정맥도플러초음파에서좌하지심부정맥혈전이확인되었다 (Figure 3). 2년 6개월간항응고제 (warfarin) 투약및경과관찰하였으며추적관찰한흉부전산화단층촬영에서폐색전증은관찰되지않았으며하지정맥도플러초음파에서대부분의심부정맥혈전이사라졌다. 다른 3명의증례에서증상은흉부압박감과기침, 객혈, 흉통이었으며위험인자로생각할수있는베체트병 (echet disease), 갑상선종과십자인대손상으로인한수술기왕력, 장시간의버스여행이있었다. 폐경기여성으로 6년 4개월, 2년 10개월, 3개월간호르몬제제를복용하였다. 단순흉부 X-선촬영에서우상엽에쐐기모양의증가된음영이 1증례에서관찰되었으며 (Fig. 1), 흉부전산화단층촬영에서 2증례의우상엽폐색전증이관찰되었다. 1증례에서폐관류주사영상을시행하여우상엽과우하엽에관류결손을확인하였다. 하지정맥도플러초음파에서심부정맥혈전이 2증례에서관찰되었다 (Figure 3). 1년 2개월에서 3년간항응고제 (warfarin) 투약및경과관찰하였으며추적관찰한흉부전산화단층촬영에서폐색전증은관찰되지않았으며하지정맥도플러초음파에서정맥혈전은관찰되지않았다. 결과연구대상환자는평균나이가 58.2±0.5세의폐경기여성이었다. 폐색전증을진단받기전짧게는 3개월에서 5년 8개월동안저용량에스트로겐을포함한호르몬대체요법을받았다. 호르몬제는에스트로겐-프로게스테론병합요법 2명과에스트로겐단독요법이 3명이었다. 모두가폐경기증상완화를목적으로하여피임제에포함된에스트로겐용량보다 3-4배적은용량이었다. 임상양상으로객혈, 호흡곤란, 흉부압박감이각 1명, 흉통이 2명으로일반적인폐색전증과유사하였다. 3명의환자에게하지부종, 통증등의심부정맥혈전증의증상이동반되었다. 호르몬요법외에다른위험인자로는십자인대손상에의한장기간침상안정과수술, 비만, 장시간의여행, 당뇨, 베체트병 (echet disease) 등이있었다 (Table 1). 단순흉부 X-선촬영에서늑막액저류와쐐기모양의증가된음영이각 1 명에서관찰되었다. 흉부전산화단층촬영과폐관류주사에서 2명의폐경색과 3명의폐색전증이관찰되었다. 2명에서양측에다발성으로발생하였으며 3명에서우측에발생하였다. 하지정맥도플러초음파에서대퇴동맥에서 2명과장골동맥에서 1명의하지심부정맥혈전증이관찰되었다 (Table 2). 고찰호르몬요법은홍조, 야간발한, 비뇨기계증상등폐경기증상의개선및골다공증예방을위해 1990년대이후광범위하게사용되었다. 폐경기후호르몬요법은기존의에스트로겐호르몬피임제와달리에스트로겐농도가낮기때문에혈액응고부작용은거의없다고알려졌었다 4. 그러나호르몬요법에의한부작용으로심혈관질환, 유방암, 자궁내막암, 뇌졸중위험도의증가는많은연구를통해증명되었다 1-3,5. 또한호르몬요법에의한폐색전증은폐경기후호르몬요법이광범위하게이루어진뒤점차보고가증가하고있다. 에스트로겐단독요법과에스트로겐-프로게스테론병합요법을비교한연구에서에스트로겐단독요법이심부정 365

5 SY Kim et al: Pulmonary thromboembolism after post-menopause hormonal replacement therapy 맥혈전증등위험도가더낮게보고되었다 2,3,7. 본연구에서도에스트로겐-프로게스테론병합요법을한경우 5개월만에폐색전증이발생되었다. 상대적으로젊은여성에게호르몬요법부작용위험도가더낮게보고되었다 3. 다른연구에선피하주사호르몬요법이경구복용호르몬요법에비해심부정맥혈전증등의위험도가낮다고보고되었다 5,7. 고용량호르몬요법보다저용량요법에서심부정맥혈전증의위험도는낮게보고되었다 3,7-11. 폐경기후호르몬대체요법의부작용은호르몬요법후 1년이내에가장흔히발생된다 7. 폐색전증은 1시간내에 10% 의사망률을보이는질환으로빠른진단과치료를필요로한다 3,12. 폐색전증의위험도가증가하는것은호르몬제제가혈액내응고와혈전용해기전의불균형을초래하기때문이다 6. 그위험도는 2-4.5배이상상승한다 7. 그외의일반적으로잘알려진심부정맥혈전증및폐색전증의위험인자인고령, 비만, 하지정맥류등이동반된여성에게호르몬요법시폐색전증의위험도는더욱증가할것이다. 본연구에서도장시간안정을취한경우와기저질환으로혈관이상을초래할수있는당뇨병, 베체트병 (echet disease) 등이위험인자로추정된다. 모든환자는항응고제 (lower molecular weight heparin) 를통한치료를하였으며임상적으로호전되었다. 호르몬요법은중단하였으며치료종료후추적관찰기간동안폐색전증은재발되지않았다. 본연구결과에서보듯이호르몬요법외에다른위험인자가있을경우폐색전증발생빈도가증가할것으로생각된다. 그러므로폐색전증의위험인자가있는경우호르몬요법치료에특별한주위를요한다. 또한호르몬요법치료가광범위하게이루어지고있는현실정에비추어호르몬요법치료중철저한감시가필요하며향후이에대한대규모연구가진행되어야할것으로생각된다. 요약폐경기여성에서호르몬대체요법은폐경기증상의경감, 골다공증에의한골절, 대장암의위험도감소등의효과가인정되어왔다. 현재도많은폐경기여성 에게사용되어지고있는치료법이다. 그러나그에따른부작용또한점차밝혀지며연구되고있다. 이러한부작용중생명을위협할수있는폐색전증은호르몬요법을사용할시항상각별한주의를요한다. 폐경기호르몬대체요법이필요할경우심부정맥혈전증과폐색전증의다른위험인자나환경적요인등을가진환자에게그사용에있어더욱주위를기울여야한다. 또한폐색전증의가장많은증상인호흡기증상이있을경우즉시적절한평가와치료가필요하다. 참고문헌 1. Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 1996;348: Douketis JD, Julian J, Kearon C, nderson DR, Crowther M, ates SM, et al. Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? prospective case-control study. J Thromb Haemost 2005;3: Nelson HD, Humphrey LL, Nygren P, Teutsch SM, llan JD. Postmenopausal hormone replacement therapy. JM 2002;288: ae SJ, Kim JS, Kim JH, Yun YJ, Lee S. case of venous thrombosis developed in a woman taking oral contraceptives with antithrombin III, protein C and protein S deficiencies. Korean J Obstet Gynecol 2006;49: Scarabin PY, Oger E, Plu-ureau G. Differential association of oral and transdermal oestrogenreplacement therapy with venous thromboembolism risk. Lancet 2003;362: arlow DH. Hormone replacement therapy and the risk of deep vein thrombosis. Int J Gynecol Obstet 1997;59:S29-S Wu O. Postmenopausal hormone replacement therapy and venous thromboembolism. Gender Medicine 2005; 2:S18-S Lidegaard O, Edstrim, Kreiner S. Oral contraceptives and venous thromboembolism. casecontrol study. Contraception 1998;57: Vessay M, Mant D, Smith, Yeates D. Oral contraceptives and venous thromboembolism: findings in a large prospective study. r Med J 1986;292: Gerstman, Piper JM, Freiman JP, Tomita DK, Kennedy DL, Ferguson WJ, et al. Oral contraceptive estrogen and progestin potencies and the incidence of 366

6 Tuberculosis and Respiratory Diseases Vol. 63. No.4, Oct deep venous thromboembolism. Int J Epidemiol 1990;19: Gerstman, Piper JM, Tomita DK, Ferguson WJ, Stadel V, Lundin FE. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. m J Epidemiol 1991;133: Jick H, Derby LE, Myers MW, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet 1996;348:

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