Androgen Deficiency in Aging Males 설문지와 Aging Males' Symptoms Scale 간의상관관계및혈청테스토스테론과의관련성 Correlation between Androgen Deficiency on the Aging Males Questionnaire and the Aging Males Symptoms Scale and Their Relatiohip with Serum Testosterone Dong Soo Park, Tae Beom Kim 1, Ja Hyun Ku, Soo Woong Kim, Jae-Seung Paick From the Department of Urology, Seoul National University College of Medicine, Seoul, and 1 Department of Urology, Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea Purpose: The aim of this study is to analyze the correlation between the Androgen Deficiency in Aging Males (ADAM) questionnaire and the Aging Males Symptoms (AMS) scale and to determine their relatiohip with the serum testosterone level. Materials and Methods: We retrospectively reviewed the medical records of the patients who took the self-administered ADAM questionnaire, the AMS scale and the International Index of Erectile Function (IIEF) questionnaire. We enrolled a total of 265 patients older than 40 years who presented a positive result for the ADAM questionnaire (defined as a yes awer to question 1 or 7, or a yes awer to at least three of the other questio). Blood tests were performed, including the total testosterone, prolactin, the lipid profiles and the fasting glucose level. Results: The psychological subscale of the AMS scale was correlated with ADAM questio 2, 3, 5, 7, 8 and 10 (p<0.005) and the somato-vegetative subscale was correlated with questio 2, 3, 5, 6, 8 and 10 (p<0.05). The sexual subscale was correlated with questio 1, 2, 5, 6, 7, 8 and 10 (p< 0.05). Statistically significant differences were found for the IIEF questionnaire scores between the patients with yes and no awer to ADAM question 1 and 7 (p<0.05). The IIEF questionnaire scores were significantly lower for the men with a sexual subscale score 11-25 on the AMS scale (p<0.05). The total testosterone was not correlated with the ADAM, AMS and IIEF questionnaire but the total testosterone demotrated a significantly negative correlation with weight, abdominal circumference, body mass index (BMI) and triglyceride (p<0.05). Conclusio: This analysis revealed that the ADAM questionnaire and the AMS scale have a significant relatiohip, and especially the sexual function domain of the two questionnaires showed correlation with the IIEF questionnaire. Serum testosterone was related with weight, abdominal circumference, BMI and triglyceride. (Korean J Urol 2008;49:1035-1040) Key Words: Hypogonadism, Questionnaires, Testosterone 대한비뇨기과학회지제 49 권제 11 호 2008 서울대학교의과대학비뇨기과학교실, 1 가천의과대학교길병원비뇨기과학교실 박동수ㆍ김태범 1 ㆍ구자현김수웅ㆍ백재승 접수일자 :2008년 7월 8일채택일자 :2008년 7월 17일 교신저자 : 백재승서울대학교병원비뇨기과서울시종로구연건동 28 번지 110-744 TEL: 02-2072-2422 FAX: 02-742-4665 E-mail: jspaick@snu.ac.kr 서 폐경기와같이여성에서발생하는내분비계변화는남성 론 에게서도발생하며이는혈청테스토스테론의저하와연관된다. 1 노인남성에서혈청테스토스테론이감소함에따라생활활력도, 근력, 성욕, 수면중발기, 골밀도등의감소와복부지방, 인슐린저항성의증가가흔히발견되며테스토 1035
1036 대한비뇨기과학회지 : 제 49 권제 11 호 2008 스테론을보충하면근력과성욕등의향상이여러연구에서보고되었다. 2-8 테스토스테론의저하와관련된증후군은 andropause, Androgen Deficiency in Aging Males (ADAM), Partial Androgen Deficiency in Aging Males (PADAM), testosterone deficiency syndrome 등으로불려져왔으며최근에는 late oet hypogonadism (LOH) 으로불려지고있다. 9 일반적으로 LOH의진단은호르몬검사와설문지조사로이루어진다. 그러나 LOH의진단을위한호르몬검사의진단기준은아직까지정립되지않았고노화에따른남성호르몬의변화도개개인마다일정하지않으며, 10 노화와관련된증상이남성호르몬의감소에의한것인지도분명치않다. 그러므로 LOH의임상적진단을용이하게하기위해현재까지 3가지의설문지가개발되었다. ADAM 설문지는 2000년 Morley 등 11 에의해개발되어 40 세이상의남성에서남성호르몬결핍상태를선별할수있는진단검사로서의타당도가입증되었고진단의민감도가높아선별검사로서흔히사용되며, 2004년 Kim 등 12 에의해한국어번역본이개발되었다. Aging Males Symptoms (AMS) scale는노화가삶의질에미치는영향을평가하기위해 1999년 Heinemann 등 13 에의해개발되어타당도와신뢰도가입증되었으며 2003년 Daig 등 14 에의해한국어로번역되었다. Massachusetts Male Aging survey (MMAS) 는 2000년 Smith 등 15 에의해고안되었지만한국어번역본이없어국내에서는거의사용되지않는다. 최근까지 ADAM 설문지와 AMS scale 간의상관관계를밝힌연구가거의없기에저자들은두설문지간의상관관계를조사하고이설문지들이실제환자들의테스토스테론농도와국제발기능지수 (International Index of Erectile Function; IIEF) 와관련성이있는지알아보고자하였다. 대상및방법 2006년 3월부터 2007년 5월까지발기력감소, 무기력등의남성갱년기증상을주소로본원을방문하여 ADAM, AMS, IIEF 설문지를자가기입한환자를대상으로하였다. 대상환자들의병력청취를통하여이전에테스토스테론보충요법을시행받은환자와제5형 phosphodiesterase 억제제 (PDE5I) 를복용중인환자, 노인성우울증으로진단받고항우울제를복용중인환자는제외하였고 40세이상이며 ADAM 설문지에서양성, 즉성욕감퇴를평가하는 1번문항또는발기력감퇴를평가하는 7번문항에 예 라고답하거나다른 3개이상의문항에대해 예 라고응답한 265명의환자를대상으로하였다. AMS scale는 psychological subscale, somato-vegetative subscale, sexual subscale로구분하였 고, AMS 총점수가 29점이상인경우양성반응으로판단하였다. IIEF 설문지는발기능영역, 절정감영역, 성적욕구영역, 성교만족도영역, 전반적만족도영역으로구분하였고발기능영역의점수가 26점미만인경우발기력의장애가있는것으로판단하였다. 모든대상환자들은오전 8시부터 11시사이에정맥혈을일회채취하여혈청테스토스테론, 프로락틴, 총콜레스테롤, 중성지방, HDL 콜레스테롤, LDL 콜레스테롤, 공복시혈당을측정하였다. 통계분석은 SPSS version 13.0 (SPSS, Inc., USA) 을이용하여 correlation analysis를수행하였고 p값이 0.05 미만인경우를통계학적으로의미가있다고판정하였다. Table 1. Patients characteristics Variable 결 대상환자의연령, 체질량지수 (body mass index; BMI), 혈청테스토스테론, 프로락틴, 총콜레스테롤, 중성지방, HDL 콜레스테롤, LDL 콜레스테롤, 공복시혈당의평균값은각각 59.9±8.4세, 24.5±2.8kg/m 2, 5.0±2.1ng/ml, 183.1±48.2mg/dl, 142.3±84.5mg/dl, 55.7±84.5mg/dl, 112.0±33.2mg/dl, 106.2±31.9 Age (years) Height (cm) Weight (kg) BMI (kg/m²) Testosterone (ng/ml) Prolactin (ng/ml) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) Fasting glucose (mg/dl) AMS scale Psychological subscale Somato-vegetative subscale Sexual subscale Total score IIEF questionnaire Erectile function domain Sexual satisfaction domain Orgasmic function domain Sexual drive domain Overall satisfaction domain Total score Mean±SD 59.9±8.4 171.5±34.6 70.6±8.9 24.5±2.8 5.0±2.1 5.8±7.0 183.1±48.2 142.3±84.5 55.7±84.5 112.0±33.2 106.2±31.9 12.3±4.5 16.7±5.5 16.8±6.7 45.5±11.5 10.1±9.0 4.0±3.7 3.7±3.7 4.0±2.2 3.7±2.0 25.6±19.4 SD: standard deviation, BMI: body mass index, HDL: high deity lipoprotein, LDL: low deity lipoprotein, AMS: Aging Males Symptoms, IIEF: International Index of Erectile Function 과
박동수외 :ADAM, AMS Scale 간의상관관계및테스토스테론과의관련성 1037 mg/dl였다. 대상환자중 AMS scale에서양성반응을보인환자는 93.2% (247명) 였고 AMS scale의 psychological subscale, somato-vegetative subscale, sexual subscale의평균값은각각 12.3±4.5, 16.7±5.5, 16.8±6.7, 총점수의평균값은 45.5± 11.5였다. IIEF에서발기력장애를보인환자는 92% (244명) 였고각영역별평균값은각각발기능영역 10.1±9.0, 절정감영역 3.7±3.7, 성적욕구영역 4.0±2.2, 성교만족도영역 4.0±3.7, 전반적만족도영역 3.7±2.0이었고, 총점수의평균값은 25.6±19.4였다 (Table 1). AMS scale의 psychological subscale는 ADAM 설문지의 2-3번, 5-8번, 10번문항과상관관계를보였으며, somatovegetative subscale은 ADAM 설문지의 2-3번, 5-6번, 8번, 10 번문항과상관관계를보였고, sexual subscale는 ADAM 설문지의 1-2번, 5-8번, 10번문항과서로상관관계를보였다 (p<0.05). 그러나 ADAM 설문지의 4번문항과 9번문항은 AMS의 3개 subscale 모두와상관관계를보이지않았다 (Table 2). ADAM 설문지 1번문항에 예 라고응답한경우 IIEF 설 문지의 5개의영역모두유의하게낮은점수를보였으며 7번문항에 예 라고응답한경우성적욕구영역과전반적만족도영역의점수가유의하게낮았다 (p<0.05) (Table 3). AMS scale의 sexual subscale이 severe (score 11-25) 인경우 IIEF의발기능영역, 성교만족도영역, 전반적만족도영역의점수가유의하게낮았다 (p<0.05) (Table 4). 대상군의혈청테스토스테론농도는 ADAM 설문지의 10 개문항, AMS scale의 3개 subscale, IIEF의 5개영역의평가결과와는유의한관련이없었으며, 테스토스테론농도는체중, 복부둘레, BMI, 중성지방농도와통계적으로유의한음의상관관계를보였다 (p<0.05) (Table 5). 고찰고환과부신에서분비되는테스토스테론은성인이전에는외성기의남성화와이차성징의발현에역할을하고성인이된후에는성기능에중요한역할을한다. 혈청테스토스테론은 20-40대에최고치에도달하고이후에는감소하는 Table 2. Correlation between the ADAM questionnaire and the AMS scale ADAM questionnaire Decreased libido Lack of energy Decreased strength and/or endurance Loss of height Decreased enjoyment of life Sad and/or grumpy Erectio less strong Deterioration in ability to play sports Falling asleep after dinner Deterioration in work perfor-mance 0.010 0.313 0.258 0.039 0.279 0.493 0.121 0.306 0.050 0.324 AMS psychological AMS somatovegetative AMS sexual r p-value r p-value r p-value 0.874 0.528 0.048 0.416 AMS: Aging Males Symptoms, ADAM: Androgen Deficiency in Aging Males 0.023 0.349 0.274 0.045 0.138 0.353 0.098 0.375 0.064 0.356 0.706 0.463 0.023 0.108 0.300 0.176 0.334 0.097 0.114 0.203 0.217 0.217 0.149 0.056 0.350 0.004 0.113 0.063 0.001 0.015 0.365 Table 3. Correlation between the ADAM questionnaire questio 1 and 7 and the IIEF questionnaire IIEF questionnaire Eretile function Sexual satisfaction Orgasmic function Sexual drive Overall satisfaction ADAM 1 ADAM 7 Yes No p-value Yes No p-value 9.8±8.8 3.8±3.7 3.6±3.7 3.9±2.1 3.6±1.9 15.2±9.9 5.7±3.7 5.4±3.7 5.3±2.7 5.0±2.3 0.004 0.017 0.026 0.020 0.001 ADAM: Androgen Deficiency in Aging Males, IIEF: International Index of Erectile Function 9.7±8.9 3.9±3.7 3.6±3.7 3.9±2.1 3.6±2.0 13.4±10.3 5.3±4.2 5.0±4.2 5.1±2.3 4.7±2.3 0.074 0.094 0.107 0.014 0.026
1038 대한비뇨기과학회지 : 제 49 권제 11 호 2008 Table 4. Correlation between the sexual subscale of the AMS scale and the IIEF questionnaire IIEF questionnaire Eretile function Sexual satisfaction Orgasmic function Sexual drive Overall satisfaction Sexual subscale of AMS scale Severe (11-15) 9.8±8.8 3.9±3.6 3.7±3.7 4.0±2.1 3.7±2.0 Not severe (5-10) 14.2±10.9 5.8±4.4 4.8±4.2 4.9±2.4 4.8±2.3 p-value 0.048 0.041 0.243 0.094 0.020 AMS: Aging Males Symptoms, IIEF: International Index of Erectile Function 데, MMAS의결과에의하면유리테스토스테론은매년 1.2% 씩, albumin에결합한테스토스테론은 1.0% 씩감소한다. 16 남성호르몬결핍의일반적생화학적기준은총테스토스테론 3.25mg/ml 이하, 유리테스토스테론 200pg/ml 이하이다. 노화에따른테스토스테론의감소치는 10년마다 110 ng/ml 정도라는연구가있고, 17 2004년미국에서는 40세이상남성에서 1년에약 48만명에서남성호르몬결핍이발생한다고연구도보고되었다. 18 최근우리나라도고령사회로진입하고있으며이에따라노인남성에서의남성호르몬결핍에대한관심이고조되고있으나아직까지그진단에대한일치된견해가부족한실정이다. 본연구가비교하고자하였던 ADAM 설문지는 Morley 등 11 이자신들의임상경험을근거로대표적인 10가지증상들을포함하여개발한설문지로서성욕감퇴나발기력저하를평가하는 1번또는 7번문항에 예 라고응답하거나, 다른문항 3가지이상에 예 라고응답한경우를양성반응으로규정하고있다. Morley 등 11 은 40세이상의남성캐나다인 316명을대상으로생체이용가능한테스토스테론을측정하여 70ng/dl 미만인경우를남성호르몬결핍이있는것으로판단하였고 ADAM 설문지에대한양성반응률과비교한결과 ADAM 설문지의진단민감도는 88%, 진단특이도는 60% 라고하였다. 또한남성호르몬보충요법을시행받은후의치료결과를객관적으로평가할수있는도구로서도유용성을입증하였다. Martı nez-jabaloyas 등 9 은 50세이상의스페인남성을대상으로 ADAM 설문지와연령, 당뇨, 호르몬등을전향적으로조사하여 ADAM 설문지에서양성반응은당뇨, 연령과관련이있고, 양성반응을보인환자에서유리테스토스테론, DHEA-S 농도는유의하게낮았으며, 혈청총테스토스테론은 ADAM 설문지의양성반응과관련이없다고보고하였다. 그리고유리테스토스테론이 0.228 nmol/l 미만일경우남성호르몬결핍상태로정의하면남성 Table 5. Relatiohip with serum testosterone Variable r p-value Age Height Weight Abdominal circumference BMI Triglyceride AMS scale ADAM questionnaire IIEF questionnaire 0.042 0.063 0.205 0.204 0.191 0.197 0.001 0.002 0.002 0.005 BMI: body mass index, AMS: Aging Males Symptoms, ADAM: Androgen Deficiency in Aging Males, IIEF: International Index of Erectile Function, : not significant 호르몬결핍의유병률은 24.6% 였고 ADAM 설문지의진단민감도와특이도는각각 84% 와 36.6% 라고하였다. Tancredi 등 19 은유리테스토스테론의절단값 (cut-off value) 을 70ng/dl 로하였을때 ADAM 설문지의진단민감도는 81%, 특이도는 21.6% 로보고하였다. 1999년 Heinemann 등 13 이독일어로개발한 AMS scale는노화가남성의삶의질에미치는영향을객관적으로평가하기위해고안된설문지이다. 40세이상건강한남성 116 명을대상으로 21개의노화와관련한증상을수집한후 40 세이상 992명의남성을대상으로노화와수반된 17개의대표증상을정리하여 psychological, somatovegetative, sexual subscale로세분화하여그타당도를입증하였다. 이설문지는 1) 노화과정에수반되는증상들을다루고있고, 2) 그제반증상의심한정도를 5점척도로평가하였으며, 3) 남성호르몬치료전후의변화를객관화할수있는장점이있다. 2005년 Basar 등 20 은 348명의환자를대상으로 AMS scale, IIEF 설문지, 호르몬등을조사하였다. AMS 총점수 29점이상을노화와수반된양성반응으로규정하고 IIEF 점수 26점미만을성기능부전이있는것으로정의하였을때, AMS scale에서양성반응을보인환자는그렇지않은환자에비해나이, DHEA-S, E2, AMS scale 총점수와 subscale 점수에서유의한차이를보였다. 또한성기능부전이있는환자들은나이, DHEA-S, 유리테스토스테론, IIEF 점수, AMS scale 총점수와 subscale 점수에서유의한차이를보였다. 그러나총테스토스테론은어느것과도연관이없었다고보고하였다. 2006년 Heinemann 등 21 은남성호르몬결핍환자 1,670명에게 12주동안테스토스테론겔을투약한후 AMS scale 총점수, psychological subscale 점수, somato-vegetative subscale 점수, sexual subscale 점수가투약전에비해각각 30.7%, 27.3%, 30.5%, 30.7% 향상된것을보고하였고증상
박동수외 :ADAM, AMS Scale 간의상관관계및테스토스테론과의관련성 1039 이심할수록투약후반응이좋은경향을보였다고보고하였다. 2005년 Morley 등 22 은남성호르몬결핍상태를생체이용가능한테스토스테론이 70ng/ml 이하일때로정하고, ADAM, AMS, MMAS 설문지를비교하였는데각설문지의진단민감도는각각 97%, 83%, 60%, 특이도는각각 30%, 39%, 59% 라고하였다. 그리고각설문지를통해양성반응을보인환자들은유리테스토스테론, 생체이용가능한테스토스테론에서유의한차이를보였으나총테스토스테론은차이가나지않았다고보고하였다. 이처럼 ADAM 설문지와 AMS scale는높은진단민감도로인해남성호르몬결핍상태가의심되는환자에서선별검사로서흔히이용되지만특이도가낮고총테스토스테론과의관련은없다고알려져있다. 저자들의결과에서 ADAM 설문지의 10개의문항중 4번 신장이줄었습니까? 와 9번 저녁식사후바로잠에빠져드십니까? 를제외한 8개문항은 AMS scale의각 subscale과유의한연관성을보였다. 그리고 ADAM 설문지의 1번문항 성욕감퇴가있습니까? 는 AMS sexual subscale과유의한연관을보이고 1번문항에 예 라고응답한환자들은 IIEF 설문지의모든영역의점수가유의하게낮았다. 7번문항 발기가예전보다덜강합니까? 도역시 AMS sexual subscle과유의한연관을보이고 예 라고응답한환자들은 IIEF 설문지의성적욕구영역과전반적만족도영역에서유의한차이를보였고발기능영역과성교만족도영역에서는통계적으로유의하지는않지만점수가낮은경향을보였다. AMS sexual subscale의점수가 11점이상인환자들은발기능영역과성교만족도, 전반적만족도영역에서통계적으로유의한차이를보였고절정감영역과성적욕구영역의점수도유의하지않지만낮은경향을보였다. 이는 ADAM 설문지와 AMS 설문지의성기능관련부분은 IIEF 설문지와도상당한연관성을보인다는것을의미한다. 하지만대상군의혈청테스토스테론농도와 ADAM 설문지의 10개의문항, AMS scale의 3개의 subscale, IIEF의 5개영역의평가결과와는유의한관련이없었다. Morley 등 23 도혈청테스토스테론은유리테스토스테론이나생체이용가능한테스토스테론에비해남성호르몬결핍을진단하는데부정확하다고보고한바있다. 본연구는몇가지제한점을지니고있다. 첫번째, 본연구의대상환자들이모두 ADAM 설문지에서양성으로평가된환자이다. 본연구가남성갱년기증상으로외래를방문한환자를대상으로설문조사를하였기때문에대부분의대상군이 ADAM 설문지에서양성반응으로평가되어음성으로평가된환자와의비교를할수없었다. 두번째는남성 갱년기증상은매우비특이적이고노인성우울증환자에서도비슷한증상이나타난다는것이다. 본연구에서는병력청취를통해노인성우울증환자로진단받고치료중인환자는제외를하였지만진단받지않은우울증환자를배제할수있는설문조사를시행하지않아결과의혼선을가져올여지가남아있다. 세번째는혈청테스토스테론외의호르몬검사들이평가되지않았다는점이다. 유리테스토스테론, 생체이용가능한테스토스테론, E2, DHEA-S 등의호르몬들이남성호르몬결핍의증상과연관되어있다는보고들이많으므로향후이에관한연구가필요하다고생각한다. 결 ADAM 설문지, AMS scale는서로항목들간유의한상관관계를보였으며특히성기능관련영역은 IIEF 설문지와도유의한연관성을보였다. 하지만이들설문지는남성갱년기증후군이의심되는환자에서테스토스테론의저하를예측하지는못했으며테스토스테론저하는체중, 복부둘레, 체질량지수, 중성지방농도와관련이있었다. 론 REFERENCES 1. Werner AA. The male climacteric. J Am Med Assoc 1939; 112:1441-3 2. Morley JE, Kaiser F, Raum WJ, Perry HM 3rd, Flood JF, Jeen J, et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of iulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA 1997;94:7537-42 3. Brown-Sequard CE. Effects in man of subcutaneous injectio of freshly prepared liquid from guinea pig and dog testes. C R Seances Soc Biol Ser 1889;9:415-9 4.Schiavi RC, White D, Mandeli J, Levine AC. Effect of testosterone administration on sexual behavior and mood in men with erectile dysfunction. Arch Sex Behav 1997;26: 231-41 5. Janowsky JS, Oviatt SK, Orwoll ES. Testosterone influences spatial cognition in older men. Behav Neurosci 1994;108: 325-32 6. Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 1995;269:E820-6 7. Sih R, Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab
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