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약품 분류군 영문성문명 주성분코드 제품코드 한글제품명

GONADOTROPIN S AND

ANTIGONADOTR OPINS

leuprorelin 182601BIJ 644200180 루크린주

　 　 182602BIJ 696300381 루프린주3.75mg

　 　 182602BIJ 641601192 루피어데포주3.75mg

　 　 182602BIJ 644200170 루 크 린 데 포 피 디 에 스 주 3.75mg

　 　 182602BIJ 696300391 루프린디피에스주3.75mg

　 　 182602BIJ 653400451 로렐린데포주사

　 　 182602BIJ 624900021 루크린데포주3.75mg

　 　 182602BIJ 641601191 루피어데포주3.75mg

　 　 182604BIJ 696300401 루프린디피에스주11.25mg

　 　 182604BIJ 644200160 루 크 린 데 포 피 디 에 스 주 11.25mg

　 　 182604BIJ 624900030 루크린데포주11.25mg

　 　 182604BIJ 644200140 루크린데포주11.25mg

　 　 182605BIJ 655601441 엘리가드주7.5mg

　 　 182606BIJ 655601451 엘리가드주22.5mg

　 　 182608BIJ 655601471 엘리가드주45mg

　 　 182610BIJ 624900091 루크린데포피디에스주30mg

　 　 182611BIJ 696300481 루프린디피에스주22.5mg

　 　 182630BIJ 653400461 로렐린주사액

　 goserelin 167202BIJ 650700481 졸라덱스데포주사

　 　 167201BIJ 650700491 졸라덱스엘에이데포주사

　 triptorelin 244902BIJ 652500021 데카펩틸데포주

　 　 467501BIJ 681400041 디페렐린피알주11.25mg

　 　 244930BIJ 652500031 데카펩틸주0.1mg

　 　 467502BIJ 681400141 디페렐린에스알주22.5mg

　 　 244902BIJ 681400031 디페렐린피알3.75mg주

- 34 -

　 　 244902BIJ 681400030 디페렐린피알3.75mg주

　 　 467501BIJ 681400040 디페렐린피알주11.25mg

antiandrogens bicalutamide 117201ATB 641801720 비카루드정

　 　 117201ATB 650700510 카소덱스정

　 　 117202ATB 643305110 칼루타미정150mg

　 　 117201ATB 643302750 칼루타미정50mg

　 　 117201ATB 626900610 테바비칼루타마이드정50mg

　 　 117201ATB 641901310 비카덱스정

　 　 117201ATB 658601260 비카소정

　 　 117201ATB 643501180 비칼루정

　 　 117201ATB 671806090 카덱스정

　 　 117201ATB 648503130 카소비트정

　 　 117201ATB 647802590 프로세이드정

　 　 117201ATB 652601490 프로카덱스정

　 　 117201ATB 640003750 프로칼린정50mg

　 cyproterone

139401ATB 641100680 안드로쿨정 　 flutamide 162101ATB 655501300 유렉신정250mg ANTIGONADOT

ROPINS degarelix 624402BIJ 652500352 퍼마곤주120mg

　 　 624401BIJ 652500341 퍼마곤주80mg

ESTRAMUSTIN

E estramustine 155101ACH 648901250 에스트라시트캡슐140mg

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개시일자 변경전코드 변경후코드 제품명

182602BIJ 1999-08-01 E01860061 644200150 루크린데포주3.75밀리그람 초산류프롤리드( )

244902BIJ

1999-08-01 E07560081 652500020 데카펩틸 데포 트립토렐린아세트산염- ( )

1999-08-01 E07560091 652500030 데카펩틸주0.1밀리그람 초산트립토렐린( )

2001-06-16 E20330061 681400030 디페렐린피알3.75밀리그람주 초산트립토렐린( )

167201BIJ 2002-01-01 E06610331 650700490 졸라덱스엘에이데포주사 초산고세렐린( )

167202BIJ 2002-01-01 E06610321 650700480 졸라덱스데포주사 초산고세렐린( )

182604BIJ 2002-08-01 E01860411 644200140 루크린데포주11.25mg(초산류프롤리드)

182602BIJ 2004-07-01 A04350931 641601190 루피어데포주3.75밀리그램 류프로렐린아세트산( 염)

467501BIJ 2005-02-01 E20330101 681400040 디페렐린피알주11.25밀리그람 파모산트립토렐( 린)

182604BIJ 2005-12-01 E01860541 644200160 루크린데포피디에스주11.25밀리그람 초산류프롤( 리드)

182602BIJ

2006-02-01 E01860551 644200170 루크린데포피디에스주3.75mg(초산류프롤리드)

2007-12-01 E04490201 W50460131 루프린디피에스주3.75mg

2007-12-01 E04490041 W50460021 루프린주3.75mg

2007-12-01 W50460021 640000210 루프린주3.75mg(초산류프로렐린)

182604BIJ

2007-12-01 E04490221 W50460121 루프린디피에스주11.25mg

2007-12-01 W50460121 640000190 루프린디피에스주11.25밀리그램 초산류프로렐( 린)

182608BIJ 2008-01-01 E01700211 655601470 엘리가드주 밀리그램 초산류프롤리드45 ( )

182607BIJ 2008-01-01 E01700221 655601460 엘리가드주 밀리그램 초산류프롤리드30 ( )

182605BIJ 2008-01-01 E01700231 655601440 엘리가드주7.5밀리그램 류프로렐린아세트산염( )

182606BIJ 2008-01-01 E01700241 655601450 엘리가드주22.5밀리그램 류프로렐린아세트산염( )

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2012-01-01 W50460131 640000200 루프린디피에스주3.75밀리그램 초산류프로렐린( )

2014-06-01 644200150 624900020 루크린데포주3.75밀리그람 초산류프롤리드( )

182604BIJ 2014-08-01 644200140 624900030 루크린데포주11.25mg(초산류프롤리드)

182610BIJ 2014-10-01 644206230 624900090 루크린데포피디에스주 밀리그램 류프로렐린아30 ( 세트산염)

- 37 - 대 상 자 수 치매 신환자

명(%) 명(%) HR†

(95% CI) P-value 사용

ADT

비사용군 3,648 (100%) 298 (8.17%) Reference - 사용군 192 (100%) 22 (11.46%)

( ) 0.4936

- 38 -

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ABSTRACT

Effects of Antiandrogen Treatment on Dementia Occurrence in case of Prostate Cancer Patients

Research Background

According to the 2017 National Cancer Registration Statistics, the incidence rate of cancer has declined since 2011, but cancer rate in 2017 was increased compared to the previous year except gastric cancer and colorectal cancer. In particular, the prostate cancer rate of males showed the highest growth at 7.1%.

As compared to the international survival rate of major cancers in 5 years, the survival rate of prostate cancer is 97.4% in the United States of America and it is 89.9% in Korea, so that the survival rate of that cancer is much higher than the other cancer types.

Because of the increase of antiandrogen treatment for prostate cancer in the domestic, long-term safety assessment should be needed, but it

- 40 -

is the fact that researches on large populations lack in Korea.

Therefore, this study researched effects of Androgen Deprivation Therapy (ADT) on dementia occurrence by utilizing sampling cohort data of the National Health Insurance.

Research Subjects and Methods

By using sampling cohort data of the National Health Insurance, this study extracted 3,868 subjects who had been diagnosed with prostate cancer for the first time during 6 years from 2003 to 2008, except some people diagnosed with dementia and other overlapping cancers after 1 year washing out period from 2002 to 2008. Excluding patients diagnosed with dementia from the first day of the first claim to 1 year of the landmark time, this study selected 3,868 patients as final research subjects, and 205 subjects out of them, who have ever received ADT at least once and 3,619 subjects out of them, who have never received ADT. In order to remove immortal time bias that occurs because every individual has the first diagnosis time differently of prostate cancer, this study used the landmark analysis as a statistical method. It represented the effects of ADT usage on dementia with a graph by using the Kapler-Meier survival curve, and it checked its significance with the Log-Rank test.

In order to research general characteristics of a prostate cancer patient group of ADT treatment and another prostate cancer patient group of non-ADT treatment and to investigate effects of ADT treatment on

- 41 -

dementia occurrence according to comorbidity, this study, through Cox’s proportional hazard model, verified relative risk depending on dementia occurrence. Finally, it set only statistically significant variables to dementia as interest variables and distinguished sub-groups, and it suggested a hazard ratio, 95% confidence interval of the hazard ratio, and p-value about the effects of ADT usage on dementia of each group.

Research Results

When covariates affecting dementia were not corrected, this study found that the ADT treatment group had a higher risk of dementia 1.558 (95% CI :0.639-1.802) compared to non-ADT treatment group, and it was a statistically significance (P-value=0.0437). However as a result of conducting Cox regression analysis after correcting the covariates affecting dementia (age, income level, smoking, drinking, high blood pressure, cardiovascular disease, heart failure, atrial fibrillation, cerebrovascular disease, diabetes, mental illness disorder, bipolar disorder, depression disorder, anxiety disorder, the average number of hospitalization per year, and the average number of outpatient use per year, the ADT treatment group had a higher risk of dementia compared to non-ADT treatment group as 1.154(95% CI:0.742~1.795), but there was not a statistical significance (P-value=0.5248). As a result of sub-group analysis that could affect dementia occurrence, the older research subjects become, the higher the risk of dementia tends to be,

- 42 -

and it was statistically significant. In the case of the prostate cancer patients with high blood pressure and mental illness disorder, the ADT treatment group had a higher risk of dementia than the non-ADT group, but it was not statistically significant.

Conclusion

This study verified that after correcting variables, affecting dementia of prostate cancer patients, the ADT treatment group had a higher risk of dementia as 1.154(95% CI:0.742~1.795) compared to the non-ADT treatment group but there was not a statistical significance.

(P-value=0.5248). However, in the future, if it conducts landmark analysis or time-dependent Cox regression analysis by including the longer billing data with sampling cohort data that this study utilized and making the ADT usage period and follow-up period much longer, the research would identify the effects of ADT treatment on dementia more accurately.

Although this study verified the ADT treatment could not have relation with the increase of dementia risk, it has to be careful for some prostate cancer patients with comorbidity including high blood pressure and mental illness disorder that there would be possibility of dementia occurrence when applying ADT treatment.