育齡婦女體內戴奧辛及多氯聯苯濃度與雌性素相關疾病之探討

目的: 以往研究發現，戴奧辛屬於內分泌干擾物質¥。以育齡婦女而言，暴露於戴奧辛會造成雌性素(estrogen)代謝異常。本研究目的探討此類污染物質經由雌性素功能及子宮內膜増生之相關疾病進而影響生殖功能，如子宮內膜異位症、子宮肌腺瘤或子宮肌瘤。方法: 研究方法使用配對病例-對照研究。收案時間從2005年1月~2006年12月與南部某醫學中心合作協助受試者收集。由婦產科使用腹腔鏡診斷為子宮內膜異位症與子宮肌腺瘤或子宮肌瘤患者為病例組；對照組為健康婦女或排除上述疾病。利用高解析度氣相層析儀與高解析質譜儀定量血清中戴奧辛(polychlorinated dibenzo-p-dioxins PCDDs, dibenzo-furans PCDFs)與多氯聯苯(polychlorinated biphenyls PCBs)濃度。目前受試人數72位，年齡介於25-45歲(病例組=28位,對照組=44位)，皆有檢測體內戴奧辛與多氯聯苯濃度。結果與討論: 病例組以及對照組年齡平均分別為33歲、31歲，基本特性描述結果發現月經不規律病例組佔了89%(p = 0.043) ，半年內不正常出血者佔了53.6% (p <0.001) 。初步分析病例組與對照組體內戴奧辛/多氯聯苯濃度，發現病例組Total PCDDs/DFs; Total PCBs濃度(14.45 pg TEQ/g-lipid, 8.71 vs. 11.21, 5.71):顯著高於對照組( p <0.001; p <0.05)，利用複回歸模式更進一步分析並調控年齡、肥胖指數、胎次、哺餵母乳次數仍可發現體內Total Dioxins/PCBs 濃度大於18pg TEQ/g lipid 會增加疾病風險達七倍之多(Odds ratio, 95%CI= 7.47, 1.78-31.29)。在荷爾蒙分析部分經由線性回歸調控喝酒抽菸後，病例組體內AFP(α-fetal protein)則與Total PCBs有顯著正相關(β = 0.283; p= 0.024)。目前本研究仍屬小樣本，但可清楚看到雌性素疾病體內戴奧辛/多氯聯苯濃度顯著高於對照組，對於未來應增加樣本數以及更進一步探討其中的致病機轉。

關鍵字

戴奧辛；雌性素過度釋放；芳香烴基碳水化合物；雌性素接受器

並列摘要

Objective: Previous studies showed dioxins are well established endocrine disrupters. Exposure to dioxin will cause abnormal metabolism of estrogen in women of reproductive age. We hypothesize that the pollutants may cause reproductive dysfunction by increased risk for diseases related to estrogens function and uterus endometrial proliferation, such as endometriosis, adenomyosis and leiomyoma Material and Methods: This is a matched case control study of participants surveyed in a medical center of southern Taiwan during January, 2005 and December, 2006. Cases were from Department of Obstetrics and Gynecology using laparoscopy for diagnosis of endometriosis, adenomyosis and leiomyoma. Controls were from either the same department or health check unit and free from the above three diseases. Serum levels of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzo-furans (PCDFs), and polychlorinated biphenyls (PCBs) were quantified by high resolution (HR) gas chromatography and HR mass spectrometry. The current report was based on 72 subjects aged 25~45 years (28 cases and 44 controls) with dioxins and PCBs all measured. Results and discussion: As compared to the controls, cases had high irregration of menstrual rate（89%, p=0.043）and abnormal uterine bleeding (53.6%, p<0.001).Compaired Dioxins/ PCBs concentration in case and control, Total PCDDs/DFs and PCBs are significantly higher in cases(14.45 pg TEQ/g-lipid, 8.71 vs. 11.21, 5.71) than in control( p <0.001; p <0.05, respectively). Multivarient logistic regression analyses also show significant association between the disease risk and increased Total Dioxins/PCBs levels. The disease prevalence increased 7 folds in subjects over 18 pg-TEQ/g lipid as compared to those below the level (Odds ratio, 95%CI= 7.47, 1,78-31.29) after adjustment for age, BMI, parity, and breast-feeding. In correlation analysis between dioxins and hormone, the cases AFP (α-fetal protein ) is significant positive correlation on Total PCBs (β = 0.283; p= 0.024) after adjustement for smoke and alchol. We found a clearly positive association between dioxin/PCB body burden and the esterogen denpendecy disease even with small sample size. The effect is worth of noting for reproductive dysfunction in fertility women, further studies should increase sample size and investigate mechanisms.

並列關鍵字

Dioxin, estrogen over-expression, aryl-hydrocarbon receptor (AhR), estrogen receptor

參考文獻

Google Scholar

Kitawaki J. 2006. Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best practice & research 20(4): 493-502.

Google Scholar

Kitawaki J, Kado N, Ishihara H, Koshiba H, Kitaoka Y, Honjo H. 2002. Endometriosis: the pathophysiology as an estrogen-dependent disease. The Journal of steroid biochemistry and molecular biology 83(1-5): 149-155.