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1 J Korean Diabetes 2015;16: Vol.16, No.3, 2015 ISSN , 이화여자대학교의과대학내과학교실 Epidemiology and Diagnostic Criteria of Polycystic Ovary Syndrome Hyejin Lee, Yeon-Ah Sung Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea Abstract Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by oligomenorrhea, hyperandrogenism and polycystic ovaries. The prevalence of PCOS varies between 6% and 10% depending on the diagnostic criteria and the ethnicity. Diagnosis of PCOS relies on a combination of clinical, biological and ultrasound criteria that are used worldwide in different variations. Few studies have extensively examined reproductive and metabolic characteristics and hyperandrogenism in Korean women. Despite the paucity of these studies, they are critical for ascertaining PCOS diagnostic criteria for this population. This review addresses the epidemiology and diagnostic criteria of PCOS specifically for Korean women. Keywords: Diagnosis, Epidemiology, Polycystic ovary syndrome 서론 다낭난소증후군 (polycystic ovary syndrome, PCOS) 은가임여성의 6~10% 에서발생하는흔한내분비질환으로고안드로겐증과배란이상을특징으로한다 [1]. PCOS는현재까지도통일된진단기준이확립되지않았으며, 이는다양 한병인에의해여러가지임상상으로발생함을시사한다. PCOS는무배란이나불임과연관된생식계이상으로인한문제뿐아니라, 인슐린저항성및비만으로인한제2형당뇨병, 이상지질혈증, 심혈관계질환등의문제점을가지고있다 [2,3]. 따라서 PCOS는단순한산부인과적질환이아닌대사이상을동반한내분비질환이며 [4,5], 조기에진단하 Corresponding author: Yeon-Ah Sung Department of Internal Medicine, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea, yasung@ewha.ac.kr Received: Aug. 6, 2015; Accepted: Aug. 20, 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2015 Korean Diabetes Association The Journal of Korean Diabetes 차 _JKDA 16 권 3 호 05_( ) 성연아 _ 저자 - 간행교정.indd 오후 3:36:47

2 여치료를시작하는것이필요하나환자의대부분이이병이있다는것을자각하지못하고있다. 본글은 PCOS의역학및진단기준에대해살펴보고한국여성에맞는진단기준에대한제안을하고자한다. PCOS 의진단기준 PCOS는병인이분명하지않고, 표현형또한매우다양하여 [6-9] 아직그진단기준에도논란이많은실정이며 National Institute of Children s Health and Disease (NICHD) 와 European Society of Human Reproduction and Embryology (ESHRE) 및 Androgen Excess Society (AES) 는 Table 1과같이 PCOS 의진단기준을제시한바있다 [10,11]. NICHD는희발월경과안드로겐과다가있는경우, ESHRE는희발월경, 안드로겐과다, 다낭난소중 2가지이상이있는경우, AES는안드로겐과다와난소기능이상이있는경우를 PCOS의진단기준으로제시하였다. ESHRE 기준에서는희발월경이없거나안드로겐과다가없는환자도 PCOS로진단이되며, AES 기준은희발월경이없는경우를포함하므로시상하부성무월경등도 PCOS로진단이될수있는문제가있다. 과거 PCOS의임상특징에관한보 고들이매우다양한결과를보이는이유도서로다른진단기준의사용에기인한다. 또한진단의주요요소인안드로겐과다는인종마다차이를보이며, 한국인고유의기준이없어이의개발이필요하고, 특히조모증 (hirsutism, 남성형털과다증 ) 의빈도가낮은한국에서임상적고안드로겐증의기준을정립할필요성이있다 [12]. 한국인 PCOS에게어떤진단기준을적용하는것이적절할것이며또한고안드로겐증의기준은어떻게설정하고적용할것인지결정하는것은 PCOS 환자의처치에매우중요하다. 저자들은 2,950명의가임기여성을대상으로 PCOS의진단을위한설문조사와 modified Ferriman-Gallewey (mfg) 점수로조모증검사를포함한신체검진을하였고, 초기난포기에호르몬검사와난소초음파검사및대사이상에관한검사를시행한바있다. 대조군의조모증점수 95 백분위수이상을조모증의기준으로삼을때, 서구인에서이에해당하는 mfg 점수는 6~8 점이었으며, 안드로겐과다를특징으로하는 PCOS 환자에서조모증의빈도는 50~80% 였고, 평균 mfg 점수는핀란드 8점, 독일 9.4점, 터키 12점, 영국 17점으로보고된바있다 [13-16]. 아시아에서는 mfg 3점을기준으로하여야한다는보고가있으나 [17], 아직아시아인종에서조모증의기준은확립되어있지않다. 또한아시아 PCOS 환자에서 Table 1. Various diagnostic criteria of polycystic ovary syndrome National Institute of Children s Health and Disease (1990) (both 1 and 2) 1. Chronic anovulation 2. Clinical and/or biochemical hyperandrogenism European Society of Human Reproduction and Embryology (2003) (2 out of 3) 1. Oligomenorrhea or anovulation 2. Clinical and/or biochemical hyperandrogenism 3. Polycystic ovaries Androgen Excess Society (2006) (both 1 and 2) 1. Hyperandrogenism: hirsutism and/or hyperandrogenemia 2. Ovarian dysfunction: oligomenorrhea/ anovulation and/or polycystic ovary Exclusion of other disorders (congenital adrenal hyperplasia, Cushing syndrome) 차 _JKDA 16 권 3 호 05_( ) 성연아 _ 저자 - 간행교정.indd 오후 3:36:47

3 이혜진외 조모증의빈도는 9.4~34.8% 로보고되었으나, 연구별로조모증의기준이차이가있어표준화되지못한점수이다. 필자가모집한전체여성들중 58.3% 가 0점, 30.7% 가 1~4 점, 6.3% 가 5~7점, 8점이상은 4.7% 였으며 95백분위수에해당하는점수는 7점이었다. 정상월경주기여성의 4.5%, 희발월경여성중 5.4%, 희발월경여성중 NICHD 기준으로진단된 PCOS 환자의 7.1% 에서, mfg 점수 8점이상의조모증이있었다. 한국여성의조모증점수분포와 PCOS 환자에서매우낮은조모증의유병률을감안해본다면한국인 PCOS 진단에조모증을적용하는것은진단예민도등에문제가있으며향후적절한기준점수의설정이필요할것으로생각된다. 이와같이임상적고안드로겐증의지표인조모증의진단적가치가매우낮은것을감안해볼때 PCOS 의진단을위해생화학적고안드로겐혈증기준설정은한국여성에서더욱중요하다고할수있다. 고안드로겐혈증의기준정립의중요한관건은적절한정상범위의설정이며, 이는대규모의여성을대상으로혈중테스토스테론을측정함으로써가능하다. 본연구에서는정상월경주기를가지고다낭난소의소견이없는여성 1,177명에서총테스토스테론농도를분석한결과 95 백분위수에해당하는농도는 71.9 ng/dl였으며성호르몬결합글로불린을측정하고계산한유리테스토스테론농도는 0.83 ng/dl였다. 기존연구역시대부분정상월경대조군의 90~95 백분위수이상또는평균값의 2 표준편차이상을고안드로겐혈증의기준으로삼고있으며, 연구에따라테스토스테론 60~88 ng/dl, 계산한유리테스토스테론 0.66~1.4 ng/dl를그기준으로하고있다 [18]. 한국여성에서조모증점수가다른인종에비해낮은것에비해고안드로겐혈증은인종적차이가크지않음을알수있다. 이렇게설정된고안드로겐증의기준을 PCOS의진단에적용하였을때총 2,950명중 NICHD 기준 PCOS는 494명, ESHRE 기준 1,062 명, AES 기준 648명이었고, ESHRE 진단기준에의한 PCOS 환자중 46.5% 만이 NICHD 기준에부합하였고, 61.0% 가 AES 기준에부합하여 ESHRE 기준에의한 PCOS의유병률과환자수가가장많음을알수 있다. 다양한진단기준에의해진단된 PCOS 여성들이향후어떤질병경과와합병증을보이는지전향적인관찰이필요할것이며이를통하여가장적합한 PCOS 진단기준의확립이가능할것이다. 유병률 PCOS는사춘기에임상적으로발현되기시작되며, 조기에대사이상을유발하므로조기진단이필요하나, 이를위한체계적인방안은마련되어있지않다. 저자등은약 5~ 10분이소요되는초경, 월경주기, 월경이상, 과거병력, 약물복용력, 조모증등의항목을포함한간단한선별설문을가임기여성 8,080명을대상으로시행하고, 이들중질병이있으리라고추정되는예에서 PCOS의진단을위하여조모증검진, 생식호르몬측정및난소초음파를시행하였다. 전체대상군에서희발월경은 846명 (10.5%) 이었고이중검사를시행한 281명중 125명 (44.5%) 이 NICHD 기준에의하여 PCOS로진단되었다. PCOS의추정유병률을월경횟수범주에따른총설문응답자 확진율로산출하였을때 NICHD 기준유병률 5.8%, ESHRE 기준 9.9% 였다. 이들을연간월경횟수로분류하면 6회미만, 6~7회의대상자중확진검사에의해 65.0%, 43.3% 가 PCOS로진단되었다. 연월경횟수를 10회미만으로하면 100.0% 의민감도와 78.5% 의특이도, 양성예측도 57.8%, 음성예측도 100.0% 로간단한선별설문으로조기진단에도움을줄수있을것으로생각된다. PCOS의유병률은 6~10% 로보고되어있고, 본연구자들이과거국내한의과대학여학생에서조사한유병률도 4.9% 였으며 [19] 타인종과큰차이를보이지않았다 [20-23]. 결론 PCOS 진단기준의다양성은병인의상이성을반영하므로한국인 PCOS의병인규명을통하여, 한국여성에게가장적합한질병예방과치료전략을마련하도록하여야할것 차 _JKDA 16 권 3 호 05_( ) 성연아 _ 저자 - 간행교정.indd 오후 3:36:47

4 이다. 또한여성의일생에영향을미칠수있는질환인만큼장기추적을할수있는진료체계의구축이필요할것으로생각한다. REFERENCES 1. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011;7: Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000;52: Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352: Legro RS. Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr Rev 2003; 24: Legro RS, Urbanek M, Kunselman AR, Leiby BE, Dunaif A. Self-selected women with polycystic ovary syndrome are reproductively and metabolically abnormal and undertreated. Fertil Steril 2002;78: Balen AH, Conway GS, Kaltsas G, Techatrasak K, Manning PJ, West C, Jacobs HS. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod 1995;10: Carmina E, Chu MC, Longo RA, Rini GB, Lobo RA. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab 2005;90: Park HR, Oh JY, Hong YS, Sung YA, Lee H, Cheong HW. The clinical characteristics of Korean women with polycystic ovary syndrome. Korean J Med 2007;73: Pyun GW, Choi YJ, Lee H, Oh JY, Hong YS, Sung YA, Chung HW. Phenotypic variation of polycystic ovary syndrome. J Korean Endocr Soc 2007;22: Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006;91: Franks S. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: in defense of the Rotterdam criteria. J Clin Endocrinol Metab 2006;91: Sung YA. Insulin resistance in polycystic ovary syndrome. Korean Diabetes J 2008;32: Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, Taylor K, Boots LR. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004;89: Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992;167: Landay M, Huang A, Azziz R. Degree of hyperinsulinemia, independent of androgen levels, is an important determinant of the severity of hirsutism in PCOS. Fertil Steril 2009;92: DeUgarte CM, Woods KS, Bartolucci AA, Azziz R. Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism. J Clin Endocrinol Metab 2006;91: Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne 차 _JKDA 16 권 3 호 05_( ) 성연아 _ 저자 - 간행교정.indd 오후 3:36:47

5 이혜진외 CN, Witchel SF, Norman RJ. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2012;18: Kumar A, Woods KS, Bartolucci AA, Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2005;62: Byun EK, Kim HJ, Oh JY, Hong YS, Sung YA: The prevalence of polycystic ovary syndrome in college students from Seoul. J Korean Endocr Soc 2005;20: Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89: Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90: Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999;84: Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000;85: 차 _JKDA 16 권 3 호 05_( ) 성연아 _ 저자 - 간행교정.indd 오후 3:36:47

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untitled 대한내과학회지 : 제 70 권제 4 호 2006 종 설 다낭성난소증후군의내과적진단과치료 이화여자대학교의과대학내과학교실내분비 - 대사내과 성연아 다낭성난소증후군 (polycystic ovary syndrome, PCOS) 은만성무배란과고안드로겐증을특징으로하는가임기여성에서가장흔한질환이며여성불임의가장흔한원인이다 1, 2). PCOS의병인은아직정확하게밝혀져있지않으며생식샘자극호르몬분비호르몬