J Chin Med 29(2): 51-71, 2018 DOI: 10.3966/241139642018122902004 原始論文 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 1, 1, 2, 1 1 1 1 1 1, 2, * 1 桃園長庚紀念醫院中醫部, 桃園, 臺灣 2 長庚大學中醫學系, 桃園, 臺灣 子宮內膜異位症為育齡婦女中常見的疾病之一, 臨床上常見症狀有經痛 性交疼痛及骨盆疼痛等, 子宮內膜異位症的標準診斷方式為腹腔鏡檢查, 但因腹腔鏡檢查具有侵入性及費用昂貴, 所以現多以臨床症狀加上超音波檢查 血清 CA- 125 指數等作為診斷依據及後續症狀追蹤與治療效果評估 近年來使用中醫治療子宮內膜異位症已逐漸普遍且廣為患者接受, 然而實證上卻缺乏中醫藥的有效證據 本研究案從長庚研究資料庫 (CGRD) 收集 146 名子宮內膜異位症患者之資料, 發現 68.2% 子宮內膜異位症患者併高血清 CA-125 指數患者, 接受中藥治療後其指數有下降的趨勢 ; 且 78.8% 子宮內膜異位症患者未合併高血清 CA-125 指數患者, 不因服用中藥而惡化血清 CA-125 指數, 因此保守推估中藥對於子宮內膜異位症的治療具有潛在效果, 但仍需近一步的實驗證明 另外分析臨床上最常使用的方劑分別是桂枝茯苓丸 加味逍遙散及龍膽瀉肝湯等 ; 常見與方劑配伍之單味藥物為蒲公英 香附及延胡索等, 治療方向以理血 行氣 清熱 補氣為主 關鍵字 : 子宮內膜異位症 血清 CA-125 中醫藥 前言 [1] * 通訊作者 :33378 123 03-3196200 261203-3298979 E-mail hses61077@hotmail.com # 106 年 9 月 18 日受理,107 年 7 月 6 日接受刊載
52 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 CA-125 35U/mL 3 5 CA-125 [2] CA-125 CA-125 CA-125 [3] CA-125 CA-125 CA- 125 CA-125 [4-5] CA-125 [6] CA-125 CA-125 CA-125 [2] CA- 125 CA-125 CA-125 CA-125 材料與方法 1. 資料來源 2. 研究病例篩選 2004 01 2015 12 ICD-9-CM the International Classification of Disease 9th Revision Clinical Modification 617.0 617.9 CA-125 CA-125 CA-125 CA-125 3. 統計分析 CA- 125 CA-125 CA-125
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 53 CA-125 CA-125 SAS Enterprise Guide version 4.3 t-test CA-125 p < 0.05 % % 4. 醫學倫理 2017 03 06 201700321B0 N=6781 CA-125 N =38994 N =14675 圖一收案流程圖
54 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 結果 1. 子宮內膜異位症患者就診情形 2004 1 2015 12 CA-125 16641 1966 CA-125 CA-125 146 146 CA- 125 19.52 50.83 35.15 7.11 CA-125 94 20.94 50.83 CA-125 35.53 6.88 CA-125 52 19.52 50.00 CA-125 34.46 7.52 146 10365 2983 28.78% 15.86% 1644 8.98% 931 94 CA-125 5930 52 CA-125 4435 CA-125 CA-125 p < 0.01 CA-125 CA-125 p < 0.01 146 2206 15.1 18.97 6846 12577 2. 血清 CA-125 指數前後變化 146 CA-125 CA-125 圖二中藥治療之收案標準
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 55 表一分組比較收案病患基本資料 (N=146) CA-125 CA-125 p value e (N=94) (N=52) ( ) ( )(%) ( )(%) ( )(%) ( )(%) ( )(%) ( )(%) CA-125 (U/mL) CA-125 (U/mL) 35.15 7.11 35.53 6.88 34.46 7.52 0.385 b 2983 (28.78) 1655(27.91) 1328 (29.94) 0.071 c 1644 (15.86) 1110 (18.72) 534 (12.04) <0.001 ***c 931 (8.98) 753 (12.7) 178 (4.01) <0.001 ***c 468 (4.52) 214 (3.61) 254 (5.73) <0.001 ***c 354 (3.42) 289 (4.87) 65(1.47) <0.001 ***c 50 (34.2) 33 (35.1) 17 (32.7) 0.768 c 86.14 10.52 121.91 15.12 21.47 1.31 <0.001 ***b 57.11 4.75 a 74.36 6.60 a 25.93 2.68 a p value d 0.0039 ** 0.0020 ** 0.0866 146 10365 94 CA-125 5930 52 CA-125 4435 CA-125 mean S.E.M. *** p < 0.001 ** p < 0.01 a t b t c d CA-125 e CA-125 CA-125
56 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 CA-125 CA-125 86.14 10.52 U/ ml CA-125 57.11 4.75U/mL CA-125 p < 0.01 CA- 125 94 64.38 % CA-125 121.91 15.12 U/ ml CA-125 74.36 6.60 U/mL CA-125 p < 0.01 CA-125 52 35.62% CA-125 21.47 1.31 U/mL CA-125 25.93 2.68 U/mL CA-125 p > 0.05 CA-125 CA-125 CA-125 35 CA-125 CA-125 59 CA-125 CA-125 11 CA-125 CA-125 41 94 CA-125 CA-125 35 10 25 CA-125 59 23 N = 146 ** CA-125 p < 0.01 圖三中藥治療改善子宮內膜異位症患者之血清 CA-125 指數
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 57 CA-125 CA-125 N =94 CA-125 N =52 ** CA-125 p < 0.01 圖四中藥治療改善子宮內膜異位症患者之血清 CA-125 指數 : 以初次血清 CA-125 指數分組討論 36 35 CA-125 CA-125 59 CA-125 CA-125 p > 0.05 CA-125 CA-125 p < 0.05 35 CA-125 CA-125 2628 59 CA-125 CA-125 3302 p < 0.01 3. 146 名子宮內膜異位症於治療期間常用方劑分析 CA- 125 22.73% 1556 7.41% 507 7.27 % 507 4. 146 名子宮內膜異位症於治療期間方劑類別分析 CA-
58 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 125 32.35% 2215 20.61 % 1411 14.13 % 967 表二分組比較治療前血清 CA-125 指數上升之患者 (N=94) 接受賀爾蒙藥物與後續血清 CA-125 指數之 變化 Group A (N=35) Group B (N=59) p value ( ) ( )(%) ( )(%) ( )(%) ( )(%) ( )(%) ( )(%) CA-125 (U/mL). CA-125 (U/mL) 36.26 6.65 35.10 7.04 0.434 b 541 (20.59) 1114 (33.74) <0.001 ***c 504 (19.18) 606 (18.35) 0.418 c 495(18.84) 258 (7.81) <0.001 ***c 36 (1.37) 178 (5.39) <0.001 ***c 235(8.94) 54 (1.64) <0.001 ***c 10 (28.57) 23 (38.98) 0.307 c 85.01 11.52 143.79 22.71 0.024 *b 109.99 13.09 a 53.22 5.56 a <0.001 ***b p valued <0.001 *** <0.001 *** Group A CA-125 CA-125 2628 Group B CA-125 CA-125 3302 CA-125 mean S.E.M. * p < 0.05 *** p < 0.001 a t b t c d CA-125
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 59 146 10 1556 22.73%507 7.41%498 7.27% 317 4.63%251 3.67% 183 2.67% 156 2.28%150 2.19% 135 1.97% 128 1.87% 56.69% 圖五 146 名子宮內膜異位症於中藥治療期間前 10 位常用方劑分析 146 2215 32.35% 1411 20.61% 967 14.13% 636 9.29% 223 3.26% 79.64% [34] 圖六 146 名子宮內膜異位症於中藥治療期間使用方劑類別分析
60 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 5. 146 名子宮內膜異位症於治療期間常用單味藥物分析 CA- 125 5.38 % 677 4.96 % 624 4.86 % 611 6. 146 名子宮內膜異位症於治療期間單味藥物類別分析 CA- 125 30.11% 3787 20.11 % 2529 17.24 % 2168 7. 接受中藥治療後之血清 CA-125 指數上升之藥物分析 CA-125 94 35 CA-125 488 22.56% 164 8.26% 157 7.91% 254 7.70% 146 10 677 5.38% 624 4.96% 611 4.86% 419 3.33% 394 3.13% 370 2.94% 366 2.91% 317 2.52% 306 2.43% 304 2.42% 34.88% 圖七 146 名子宮內膜異位症於中藥治療期間前 10 位常用單味藥物分析
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 61 146 3787 30.11% 2529 20.11% 2168 17.24% 1189 9.45% 213 4.24% 81.15% [35] 圖八 146 名子宮內膜異位症於中藥治療期間使用單味藥物類別分析 175 5.31% 171 5.19% CA-125 52 11 CA-125 表三接受中藥治療前之血清 CA-125 指數顯示為異常者且中藥治療後血清 CA-125 指數持續上升 (N=35) 之藥物分析, 依開立頻次遞減 (%) ( ) ( ) 488 (22.56) 1.53 0.8 3.0 164 (8.26) 1.43 0.4 3.5 157 (7.91) 1.46 0.5 3.0 129 (6.50) 1.27 0.5 2.5 69 (3.47) 1.26 0.4 2.0 254 (7.70) 0.45 0.2 2.0 175(5.31) 0.45 0.2 0.8 171 (5.19) 0.46 0.2 0.6 146 (4.43) 0.71 0.3 1.2 139 (4.22) 0.43 0.3 0.7
62 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 188 28.31% 53 7.98% 51 7.68% 86 6.40% 83 6.18% 80 5.96% CA-125 CA-125 59 CA-125 表四接受中藥治療前之血清 CA-125 指數顯示為正常者但經中藥治療後血清 CA-125 指數上升 (N=11) 之藥物分析, 依開立頻次遞減 (%) ( ) ( ) 188 (28.31) 1.69 0.8 2.2 53 (7.98) 1.45 0.8 2.0 51 (7.68) 1.51 0.8 2.5 38 (5.72) 1.42 0.4 2.0 37 (5.57) 1.71 0.5 4.0 86 (6.40) 0.42 0.2 0.5 83 (6.18) 0.33 0.1 0.5 80 (5.96) 0.47 0.3 0.6 78 (5.81) 0.47 0.1 1.5 71 (5.29) 0.48 0.2 0.6 表五接受中藥治療前之血清 CA-125 指數顯示為異常者但經中藥治療後血清 CA-125 指數下降者 (N=59) 之藥物分析, 依開立頻次遞減 (%) ( ) ( ) 600 (25.70) 1.59 0.5 3.0 213 (9.12) 1.55 0.5 3.0 199 (8.52) 1.46 0.5 3.0 99 (4.24) 1.25 0.5 2.5 83 (3.55) 1.23 0.5 2.0 259 (5.77) 0.45 0.3 0.6 223 (4.97) 0.37 0.2 0.5 183 (4.08) 0.44 0.2 0.8 170 (3.79) 0.50 0.2 1.0 161 (3.59) 0.89 0.3 3.0
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 63 表六接受中藥治療前之血清 CA-125 指數顯示為正常者且經中藥治療後血清 CA-125 指數仍為正常者 (N=41) 之藥物分析, 依開立頻次遞減 (%) ( ) ( ) 320 (17.20) 1.44 0.5 2.5 126 (6.77) 1.40 1.0 2.5 91 (4.89) 1.67 0.6 6.0 77 (4.14) 1.47 0.1 3.5 70 (3.76) 1.34 0.6 2.0 198 (5.74) 0.33 0.2 0.5 175(5.07) 0.36 0.2 0.5 123 (3.56) 0.28 0.2 0.5 100 (2.90) 0.36 0.1 0.5 98 (2.84) 0.35 0.2 0.6 146 94 32.53%64 22.15% Gestrinone Dimetriose 33 11.42%32 11.07% Danazol Ladogal 31 10.73% 27 9.34% 4 1.38% 4 1.38% 圖九 146 名子宮內膜異位症曾於西醫婦產科門診開立之賀爾蒙藥物分析
64 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 CA-125 41 8. 子宮內膜異位症患者曾接受的西藥治療 146 88 50 28% 24.32% 10.99% 32.53%22.15% Gestrinone Dimetriose 11.42% 11.07% Danazol Ladogal 10.73% 討論 1. 子宮內膜異位症之病因病機探討 [7] [8] CA-125 CA-125 [9-10] CA-125 CA-125 [11] CA- 125 CA-125 2. 中藥治療與血清 CA-125 之關係 146 94 CA-125 52 CA-125 CA-125 CA-125 CA-125 3~5 CA-125 35 CA-125 11 CA-125 CA-125
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 65 CA-125 CA-125 3. 子宮內膜異位症之常用見共病 [12] 146 CA-125 CA-125 CA-125 CA-125 CA-125 CA-125 CA-125 CA-125 [13] deep infiltrative endometriosis, DIE 5mm CA- 125 [14] ICD-9-CM ICD-9-CM 617.3 endometriosis of pelvic peritoneum 617.4 endometriosis of rectovaginal septum and vagina 617.5 endometriosis of intestine ICD-9-CM 617.9 endometriosis, site unspecified 617.0 endometriosis of uterus 617.1 endometriosis of ovary CA-125 94 CA-125 4. 94 名中藥治療前血清 CA-125 指數為異常者之分析 94 CA-125 CA-125 35 35 10 CA-125 59 59
66 中藥對於子宮內膜異位症患者血清 CA-125 指數之影響初探 23 p > 0.05 CA-125 35 CA-125 CA-125 35 CA-125 18.84% 59 7.81% 59 5.39% 35 1.37% 35 CA- 125 59 CA-125 CA-125 5. 146 名子宮內膜異位症之常用中藥方劑探討 IL2 IL-6 IL-8 MAPK p-erk VEGF [15-17] [18] CA-125 [7, 19-20] [21]
許聿榕鄭為仁高銘偵郭靜諭郭順利陳曉暐林玫君楊淑齡 67 [22] MMP-2 MMP-9 [23] [24] 6. 146 名子宮內膜異位症之常用中藥單味藥物探討 [25-26] [27] [28] [29] [30] ICAM-1 intercellular adhesion molecule-1 CD44 ICAM-1 IL-6 [7, 31] 7. 子宮內膜異位症之整體用藥分析 8. 使用中藥治療後血清 CA-125 指數上升之原因探討
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J Chin Med 29(2): 51-71, 2018 DOI: 10.3966/241139642018122902004 Original Article The Effects of Traditional Chinese Medicines in Endometriosis Patients with Screening Serum CA- 125: A Retrospective Data-Based Study Yu-Jung Hsu 1, #, Wei-Jen Cheng 1, 2 #, Ming-Chen Kao 1, Jing-Yu Guo 1, Shun-Li Kuo 1, Hsiao-Wei Chen 1, Mei-Jiun Lin 1 1, 2, *, Shu-Ling Yang 1 Department of TraditionalChinese Medicine,Center of TraditionalChinese Medicine,Chang Gung Memorial Hospital, Taoyuan, Taiwan 2 School of TraditionalChinese Medicine,College of Medicine,Chang Gung University, Taoyuan, Taiwan Endometriosis is one of the common gynecologic diseases in women of reproductive age. The most common clinical symptoms include dysmenorrhea, dyspareunia, and chronic pelvic pain. Diagnostic laparoscopy is considered the gold standard for the diagnosis of endometriosis. However, it is an invasive and expensive procedure for clinical practice, and therefore endometriosis is usually diagnosed based on clinical symptoms, sonography, and serum CA-125. In recent years, Traditional chinese Medicine (TCM) has been widely used for the treatment of endometriosis, but evidence-based studies on its efficacy remain insufficient. In this study, we collected data on 146 endometriosis patients who underwent TCM treatment from Chang Gung Research Database (CGRD) and analyzed the prescriptions. The most common formulas are Gui-zhi-fu-ling-wan, Jia-wei-xiao-yao-san, and Long-dan-xie-gan-tang, and the most common single herbs are Pu-gong-ying (Herba Taraxaci), Xiang-fu (Rhizoma Cyperi), and Yan-hu-suo (Rhizoma Corydalis). After TCM treatments, 68.2% of patients with elevated serum CA-125 level had their level decreased (p < 0.01), and 78.8% of patients with normal serum CA-125 level had their level remained normal. As a result, we assumed that TCMs have potential effects on the treatment of endometriosis via regulating blood, rectifying qi, clearing heat, and invigorating qi. However, further studies are needed to prove the efficacy of these botanical drugs. Key words: Endometriosis, CA-125, Traditional Chinese Medicine *Correspondence author: Shu-Ling Yang, Department of Traditional Chinese Medicine, Center of Traditional Chinese Medicine,Chang Gung Memorial Hospital, No. 123, Dinghu Rd., Guishan District, Taoyuan City 333, Taiwan., Tel: +886-3- 3196200 ext. 2612, Fax: +886-3-3298979, E-mail: hses61077@hotmail.com #These authors Contributed equally to this work. Received 18 th September 2017, accepted 6 th July 2018