한국 폐경 여성에서 경구 에스트로겐 종류에 따른 유방 치밀도에 대한 Medroxyprogesterone Acetate의 효과

이동윤 ( Dong Yun Lee ),최현진 ( Hyun Jin Choi ),최두석 ( Doo Seok Choi ),민용기 ( Yong Ki Min ),최연현 ( Yeon Hyeon Choe ),윤병구 ( Byung Koo Yoon ) 대한폐경학회 2010 대한폐경학회지 Vol.16 No.2

연구목적: 한국 폐경 여성에서 경구 에스트로겐 종류에 따른 medroxyprogesterone acetate (MPA)의 유방 치밀도에 대한 영향을 조사하였다. 연구재료 및 방법: Conjugated equine estrogen (CEE)+MPA 치료 (n=10) 및 estropipate+MPA 치료 (n=16)를 1년간 시행하여, 치료 전후의 X-선 유방촬영술상 유방 치밀도의 변화를 breast imaging reporting and data system (BI-RADS) 판독 및 J-image 프로그램을 이용하여 비치료 대조군 (n=27)과 함께 비교하였다. 결 과: 각 군간 기초 임상 특성의 차이는 없었다. 1년의 호르몬 치료 후, 대조군 (0%)에 비해 CEE+MPA (7/10, 70%; P<0.001) 및 estropipate+MPA (3/16, 18.8%; P=0.002) 치료군에서 유의한 유방 치밀도 증가가 관찰되었으며, CEE를 병합한 경우가 estropipate 병합군에 비해 높은 유방 치밀도 증가를 보였다 (P=0.033). NIH J image로 계산한 치밀 면적의 비율 변화는 대조군에서 0.66%, CEE+MPA 군에서 7.67%, estropipate+MPA군에서 1.48%로 차이를 보이는 경향이 있었다. 결론: 한국 여성에서 estropipate+MPA 치료는 CEE+MPA에 비해 유방 치밀도에 대한 자극 효과가 적으며, 유방 치밀도의 변화는 경구 에스트로겐의 성분에 따라 다를 수 있다. 향후 유방암 위험에 대한 추가 연구가 시행되어야 한다. Objectives: We determined if the impact of medroxyprogesterone acetate (MPA) co-administered with conjugated equine estrogen (CEE) or estropipate differed on mammographic density (MMGD) in Korean postmenopausal women. Methods: In this retrospective study, 53 healthy postmenopausal women without prior hormone therapy (HT) use were included. Smokers, habitual drinkers, women with a body mass index ≥27 kg/㎡, and women with a history of mammoplasty or breast cancer were excluded. HT using MPA (n=26) consisted of the following two groups: CEE (n=10) and estropipate (n=16). Twenty-seven untreated women served as the control group. Mammography was obtained at baseline and 1 year later, and MMGD was assessed based on the breast imaging reporting and data system (BI-RADS) by one radiologist who was blinded to treatment. In addition, the change in the proportion of the dense area after HT was assessed using the J-image program. Data were analyzed with analysis of variance and chi-square or Fisher`s exact test. Results: There were no significant differences in baseline clinical characteristics and MMGD among the three groups. After 1 year of HT, CEE (7/10 [70%]; P<0.001) and estropipate (3/16 [18.8%]; P=0.002) regimens significantly elevated the BI-RADS grade compared with controls (0%), and CEE induced a greater increase in MMGD than estropipate (P=0.033). In addition, the proportion of dense areas assessed using the J-image program increased more with the CEE regimen (7.67%) than the estropipate regimen (1.48%), but there was no statistically significant difference. Conclusion: Estropipate+MPA had a less stimulating effect on MMGD than CEE+MPA in Korean postmenopausal women. The change in MMGD induced with MPA might depend on the oral estrogen preparation. A further study on breast cancer risk based on combination HT is warranted.

측정변형율에서 동적변위 식별

신수봉 ( Shin Soobong ),윤병구 ( Yun Byung-koo ) 한국구조물진단유지관리공학회 2008 한국구조물진단유지관리공학회 학술발표대회 논문집 Vol.12 No.1

A simple algorithm is proposed for computing dynamic displacements from measured dynamic strains. A beam theory is basically applied to relate the curvature and strain. Modal superposition using general coordinates are used to relate the curvature and displacement. Theoretical mode shapes of some of the lowest modes are used in the formulation. For the current study, only beam-type structures are tested. However, the idea may be easily extended to other types of structures.

혈관 평활근세포 증식에 대한 국내 자생종 승마의 효과

강영희 ( Young Hee Kang ),이동윤 ( Dong Yun Lee ),최두석 ( Doo Seok Choi ),윤병구 ( Byung Koo Yoon ),이영주 ( Young Joo Lee ),류미라 ( Mee Ra Rhyu ) 대한폐경학회 2012 대한폐경학회지 Vol.18 No.2

연구목적: 혈관 평활근세포 증식에 대한 국내 자생종 승마의 효과를 밝히기 위해 시행되었다. 연구재료 및 방법: 3개월된 암컷 Sprague-Dawley 쥐의 대동맥으로부터 혈관 평활근세포를 얻었다. 눈빛승마, 왜승마, 세잎승마, 촛대승마 등 4종의 자생 승마를 80% ethanol, absolute methanol 그리고 40% 2-propanol을 사용하여 추출하였다. 10% fetal bovine serum (FBS)에서 배양한 혈관 평활근세포를 승마 추출물 (0.3mg/mL)로 24시간 동안 처리한 후 bromodeoxyuridine incorporation assay를 사용하여 세포증식을 조사하였다. dichlorofluorecin diacetate을 첨가한 후 flow cytometry를 이용하여 세포내 ROS 생성을 정량화하였다. 결과: 추출법이 다른 국내 자생종 승마 추출물을 처리한 결과, 혈관 평활근세포의 증식이 유의하게 23-30% 억제되었다. 또한 강력한 항산화제인 비타민 E는 10% FBS로 유도된 세포증식을 감소시켰다. 승마 추출물의 작용기전을 밝히기 위한 추가 연구 상 10% FBS에 의한 ROS 생성이 승마에 의해 감소되었다. 세포증식이나 ROS 생성에 대한 효과는 추출 방법과 승마 종에 따라 차이가 없었다. 결론: 국내 자생종 승마는 산화 스트레스 감소를 통하여 혈관 평활근세포 증식을 억제한다. 향후 다양한 심혈관계 영향에 대한 추가 연구가 필요할 것으로 사료된다. Objectives: To examine the effect of extracts of Korean native Cimicifuge species on cell proliferation in vascular smooth muscle cells (VSMC). Methods: VSMC were isolated from rat aorta. Cell proliferation was assessed by measure of bromodeoxyuridine incorporation into the cells. Differences in Reactive oxygen species (ROS) levels were examined after exposure to the extracts of Korean native Cimicifuge species using the detection reagents dichlorofluorecin diacetate. The rhizomes/roots were air-dried and milled with a commercial food mixer. Milled rhizomes/roots of each Cimicifuga species were separately extracted by 80% ethanol, absolute methanol, and 40% 2-propanol using homogenizer and evaporated under reduced pressure at low temperatures. Effects of extracts dissolved in phosphate-buffered saline (0.3 mg/mL) were examined. Results: Ethanolic, methanolic or propanolic extracts of 4 Korean native Cimicifuge species (Cimicifuga [C] davurica, C. japonica, C. heracleifolia var. bifida Nakai, C. simplex) were screened. The addition of extracts of each Korean native Cimicifuge species to cells in the presence of 10% fetal bovine serum (FBS) potently inhibited cell proliferation. Significant decrease of 23%-30% was observed. Vitamin E, a potent antioxidant, inhibited 10% FBS-stimulated cell proliferation of VSMC. We also demonstrated that extracts of each Korean native Cimicifuge species decreased intracellular ROS generation induced with 10% FBS. The effect of Korean native Cimicifuge species was not species-specific and solvent-specific. Conclusion: TExtracts of Korean native Cimicifuge species inhibit VSMC proliferation via inhibition of intracellular ROS. These findings suggest that Cimicifuge species used for reducing menopause symptoms might be cardioprotective in women.

한국 폐경 여성에서 경피 에스트로겐 겔 치료의 효과

최동석 ( Dong Seok Choi ),이동윤 ( Dong Yun Lee ),윤병구 ( Byung Koo Yoon ) 대한폐경학회 2012 대한폐경학회지 Vol.18 No.2

연구목적: 한국 폐경 여성에서 경피 에스트로겐 겔 투여 효과를 조사하였다. 연구재료 및 방법: 49명의 페경 여성에서 경피 에스트로겐 제형인 겔 (0.1%, 매일 1.5 mg 투여) 1년간 호르몬 치료를 시행하였다. 치료 3개월 뒤 폐경 증상의 호전 정도를 치료 전과 비교하였고, 부작용의 발생을 평가하였다. 체중, 체질량지수, 허리 둘레와 같은 신체측정 및 콜레스테롤, lipoprotein(a), 공복혈당, fibrinogen, C-반응성 단백질 및 deoxypyridinoline과 같은 대사 인자들을 치료 시작 3, 6, 12개월 후에 측정하여 치료 전 수치와 비교하였다. 이와 함께 치료 6개월 및 12개월 후 요추 및 대퇴 경부에서 골밀도를 측정하여 치료 시작 전과 비교하였다. 결과: 치료 3개월 후 폐경 증상이 유의하게 감소하였으며, 이 기간 동안 가장 흔한 부작용은 유방과 관련된 증상들이었고 (32.1%), 다음으로는 두통 (17.8%) 및 피부 자극 (14.3%)이 흔하였다. 1년 간의 호르몬 치료 기간 중 신체측정 결과에는 변화가 없었던 반면, 혈중 총 콜레스테롤, 저밀도 지단백, 공복 혈당 및 deoxypyridinoline 농도는 유의하게 감소하였다. 아울러, 요추 부위의 골밀도 역시 유의하게 증가하였다. 결론: 한국 폐경 여성에서 경피 에스트로겐인 겔을 이용한 호르몬 치료는 폐경 증상을 호전시키고, 대사 및 골에 유익한 영향이 있다. Objectives: To evaluate the effects of transdermal estrogen gel on postmenopausal Korean women. Methods: In this retrospective study, 49 healthy postmenopausal women were treated with transdermal gel (0.1%, 1.5 mg/day +/- progestogen) for 1 year. After 3 months of transdermal hormone therapy (HT), deviations from baseline of the global index for menopausal symptoms and the frequency of side effects were evaluated. Anthropometric factors including weight, body mass index, waist circumference, and metabolic parameters (such as serum cholesterol, lipoprotein(a), fasting glucose, fibrinogen, C-reactive protein, and deoxypyridinoline levels) were measured at baseline and after three, six, and twelve months of HT. In addition, bone mineral density was also measured at the lumbar spine and femoral neck at baseline and after six and twelve months of HT. Differences between baseline values and subsequent post-HT measurements were compared. Results: After 3 months of transdermal HT, the global index for menopausal symptoms decreased significantly (P < 0.001). Side effects within 3 months included problems related to the breast, which were most common (32.1%), followed by headache (17.8%) and skin irritation (14.3%). Anthropometric factors did not change after HT, however, metabolic parameters creased significantly. There was a notable increase in bone mineral density at the lumbar spinebut not at the femoral neck. Conclusion: Transdermal gel HT improves menopausal symptoms and metabolic parameters in postmenopausal Korean women and increases bone mineral density at the lumbar spine.

Lysophosphatidylcholine의 혈관평활근세포에 대한 세포 독성

강영희 ( Young Hee Kang ),이영주 ( Young Joo Lee ),이동윤 ( Dong Yun Lee ),유미라 ( Mee Ra Rhyu ),최두석 ( Doo Seok Choi ),윤병구 ( Byung Koo Yoon ) 대한폐경학회 2012 대한폐경학회지 Vol.18 No.3

Objectives: To investigate the cytotoxic effects of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoproteins (LDL), on vascular smooth muscle cells (VSMCs). Methods: VSMCs were derived from rat aorta. Cell death was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, lactic dehydrogenase (LDH) assay, and DNA fragmentation assay. Apoptosis was quantified by propidium iodide staining and fluorescent activated cell sorting (FACS) analysis, and intracellular free radical production was determined using 2``, 7``-dichlorofluorescin diacetate (DCF-DA). In addition, the changes in caspases, bcl-2 and bax proteins were evaluated by western blot analysis. Results: LysoPC over 25 μM induced more than 50% of the cell death at 10 hours on MTT assay with no change in the level of LDH. The DNA ladder pattern showed that cell death induced by lysoPC was caused by apoptosis, which was associated with increased free radical production. Vitamin E, a potent antioxidant and caffeic acid phenylethyl ester (CAPE), an inhibitor of nuclear factor-kappaB (NF-kB), blocked apoptosis. The casepase-3 precursor decreased and the active form of caspase-8 increased. Total bcl-2 and bax proteins did not change with lysoPC treatment, but translocation of bax from cytosole to the mitochondria membrane was observed. Conclusion: LysoPC induces apoptosis in VSMCs via an oxidant mechanism, dependent on NF-kB. (J Korean Soc Menopause 2012;18:139-146)

폐경 호르몬요법에서 경구용 Levonorgestrel 투여 1년 후 유방 치밀도에 대한 효과

위찬우 ( Chan Woo Wee ),강민정 ( Min Jung Kang ),서경용 ( Kyoung Yong Seo ),최연현 ( Yeon Hyeon Choe ),민용기 ( Yong Ki Min ),이동윤 ( Dong Yun Lee ),최두석 ( Doo Seok Choi ),윤병구 ( Byung Koo Yoon ) 대한폐경학회 2011 대한폐경학회지 Vol.17 No.1

연구목적: 한국 폐경여성에서 levonorgestrel (LNG)를 이용한 호르몬 치료의 유방 치밀도에 대한 영향을 평가하였다. 연구재료 및 방법: 후향적 연구로서, 이전에 호르몬치료 기왕력이 없는 58명을 대상으로 하였다. 23명에게 estadiol valerate (E)+LNG를 이용해 주기적으로 치료하였고, 25명의 비치료군을 대조군, 10명의 conjugated equine estrogen (CEE)+medroxyprogesterone acetate (MPA) 치료군을 양성 대조군으로 두었다. 이후 기저치와 1년 후 유방촬영을 시행하여 치밀도를 비교하였다. 치료 전후의 X선 유방촬영술상 유방 치밀도의 변화는 J-image 프로그램을 이용하여 평가하였다. 자료는 chi-square 분석 및 Fisher`s exact 분석법, 그리고 nalysis of variance (ANOVA)을 이용하여 분석하였다. 결 과: 세 군 간의 기저 임상적 특성에 차이는 없었다. 1년의 호르몬요법 후, breast imaging reporting and data system (BI-RADS) 기준에 따른 변화를 보았을 때 CEE+MPA 사용군 (77.8% [7/9])이, E + LNG 사용군 (12.5% [2/16])보다 유의하게 증가하였으나 (P=0.001), E+LNG 사용군과 비치료군 (5.3% [1/19])사이에 유의한 차이는 없었다 (P=0.446). 치밀도가 3단계인 환자만을 대상으로 한 분석에서도 E+LNG 사용군은 비치료군과 유방 치밀도 변화에 차이가 없었다. J-image 프로그램을 이용한 분석 결과도 유사한 결과를 보였다. 또한 회귀 분석 결과, 기저 치밀도와 호르몬요법후 치밀 면적의 변화 사이에는 상관 관계가 나타나지 않았다. 결론: 한국 폐경 여성에서 LNG를 이용한 호르몬요법은 유방 치밀도에 영향을 미치지 않는다. 향후 유방암 위험에 대한 추가 연구가 필요하다고 사료된다. Objectives: We evaluated changes in mammographic density (MMGD) after hormone therapy (HT) using levonorgestrel (LNG) in Korean postmenopausal women. Methods: In this retrospective study, 58 healthy postmenopausal women with no history of prior HT were included. Twenty-three women were given a cyclic regimen of estradiol valerate (E) 2 mg/day+LNG 0.075 mg/day and 25 untreated women served as a negative control and 10 women treated with continuous combined regimen of conjugated equine estrogen (CEE) 0.625 mg/day+medroxyprogesterone acetate (MPA) 2.5 mg/day as a positive control. Mammography was obtained at baseline and 1 year later, and MMGD was assessed. In addition, the change in the proportion of the dense area after HT was assessed using the J-image program. Data were analyzed with analysis of variance and chi-square or Fisher`s exact test. Results: There were no significant differences in baseline characteristics among three groups. After 1 year of HT, increase of BI-RADS grade in CEE+MPA group (7/9, 77.8%) was higher than in E+LNG group (2/16, 12.5%; P=0.001). But there was no difference between untreated group (1/19, 5.3%) and E+LNG group (2/16, 12.5%; P=0.446). In subgroup analysis of women with BI-RADS grade 3 at baseline, no significant difference. Changes in the proportion of dense areas assessed by the J-image program showed similar results. Regression analysis revealed that there was no correlation between baseline dense area and changes after HT in E+LNG group. Conclusion: HT using LNG did not influence MMGD in Korean postmenopausal women. Further study on breast cancer risk may be needed. (J Korean Soc Menopause 2011;17:27-33)