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研究生:黃家昵
研究生(外文):Chia-Ni Huang
論文名稱:一、液晶顯示器製造業職業暴露對女性員工月經週期之影響;二、液晶顯示器製造業女性員工生殖內分泌研究
論文名稱(外文):1.Occupational Hazards to Menstrual Cycle in Female Workers of LCD Manufacturing;2.Reproductive Endocrine Study in Female Workers of LCD Manufacturing
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2005
畢業學年度:93
語文別:英文
論文頁數:66
中文關鍵詞:黃體激素促濾泡成熟激素月經月經雌激素不孕症液晶螢幕顯示器製造
外文關鍵詞:luteinizing hormoneestrogensinfertilityfollicle stimulating hormoneinfertilityfemaleprogesteronemenstruationliquid crystal display manufacturing
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1.
台灣液晶顯示器製造業是一個快速發展的高科技工業,並成為全球最重要的三大液晶顯示器生產國之一。液晶顯示器製造業依其製程可分為三個階段區域如薄膜區、面板區及模組區。薄膜及面板製程與半導體製程非常類似。過去在半導體製造業所作的研究中發現,在薄膜區及離子植入區工作的女性員工,平均月經週期長度比非無塵室來得長,而週期間變異性也比非無塵室較大的現象,而在黃光區工作的女性員工,月經週期小於24天的危險性較高。而在液晶顯示器製造業所作的研究,在國際上發表的一篇研究指出,以乙二醇醚為暴露分組的依據,暴露組與非暴露組的女性員工,其月經週期長度、月經長度及月經出血量並無顯著的差異。液晶顯示器的製造過程中,會用到非常多種化學物質,其中有許多已在動物實驗上證明對女性生殖系統上的危害,卻極少在人類方面的研究。而在此製造業中亦可能暴露於其他危害性因子如電磁場、輪班工作及精神壓力等,都已證實會對女性的月經功能及生育能力造成影響。

本研究為一橫斷性研究,對國內液晶顯示器製造廠做一初步探討,評估液晶顯示器製造業女性員工職場暴露對月經功能之影響。配合該公司2002年健康檢查進行問卷調查,總共有506位女性員工完成問卷。我們利用相關資料篩選出合適的研究對象,最後總共有256位女性員工納入我們的統計分析當中。

在暴露評估方面,我們使用直讀式儀器針對無塵室三個區域做一個全面性的偵測,並利用揮發性有機化合物不鏽鋼筒被動採樣作24小時空氣採樣。另外,針對整個廠區,距離所有機台及設備30公分處作一電磁場強度的測量。空氣採樣分析結果中,發現許多採集到的揮發性有機化合物中有許多已在動物實驗上證明對女性生殖系統上的危害。在利用直讀式儀器所畫出的濃度梯度圖中顯示,模組區比起其他兩個工作區域有相當高濃度的揮發性有機化合物。在統計分析結果中,女性月經功能在於月經週期平均長度異常(小於25天或大於35天),在面板區(危險勝算比=2.34,95%信賴區間:1.00-5.49)與模組區(危險勝算比=2.55,95%信賴區間:1.10-5.91)月經平均週期長度異常危險勝算比比非無塵室高。而在月經週期平均長度小於24天方面,在模組區(危險勝算比=4.79,95%信賴區間:1.08-21.32)危險勝算比比非無塵室高。另外,在分析結果中並未發現月經週期長度與輪班工作有顯著相關。因此模組工作區多重化學物質高濃度暴露之下,例如乙醇、丙酮、苯、甲苯、二甲苯、苯乙烯可能導致女性員工月經功能的影響。後續,希望利用分析尿中荷爾蒙代謝物來提供我們更多的資訊,進一步提供職業危險因子對生育下降的影響。
2.在我們前一篇研究發現,模組工作區多種化學物質高濃度暴露之下,例如乙醇、丙酮、苯、甲苯、二甲苯、苯乙烯,導致女性員工月經功能的影響,使其在月經週期平均長度小於24天方面,在模組區(危險勝算比=4.79,95%信賴區間:1.08-21.32)危險勝算比比非無塵室高。而本篇研究即是希望利用分析尿中荷爾蒙代謝物來提供我們更多的資訊,進一步提供於液晶顯示器製造廠的職場暴露對生殖內分泌的影響。

目前,在國際上已有許多的研究,利用偵測每天尿中荷爾蒙代謝物來評估女性生殖健康及生育能力。在先前的研究中,已利用偵測每天尿中荷爾蒙代謝物的方法証明職場上的壓力、抽菸、喝酒及職業方面對生殖系統上的影響。利用此評估方法,我們可以用來測量月經週期長度、濾泡期長度、黃體期長度、排卵狀況以及荷爾蒙濃度的差異,藉此我們可以評斷暴露物質危害標的器官。

本研究為一橫斷性研究,對國內液晶顯示器製造廠做一生殖內分泌的研究,評估液晶顯示器製造業女性員工職場暴露對生殖系統的影響。月經功能是以問卷調查來量測。生殖內分泌方面,除了問卷資料及日誌並利用每天收集的尿液,偵測尿中荷爾蒙代謝物來評估。在暴露評估方面,我們使用直讀式儀器針對無塵室三個區域做一個全面性的偵測,並利用揮發性有機化合物不鏽鋼筒被動採樣作24小時空氣採樣。並針對整個廠區,距離所有機台及設備30公分處作一電磁場強度的測量。

於2003年十月開始進行問卷調查,總共有256女性員工完成問卷我們利用相關資料篩選出合適的研究對象加入後續的生殖內分泌研究當中。除了已停經、懷孕、正哺餵母乳及,有112位女性員工同意加入生殖內分泌研究。另外,研究對象會收集每天起床後的第一泡尿液並收集日誌,為期約1.5個月經週期,於2003年10月至2004年4月間完成。利用偵測尿中荷爾蒙代謝物以評估其月經功能及生育力。促濾泡成熟激素(follicle-stimulating hormone, FSH)、雌激素(estrogen)及黃體激素(progesterone)為我們主要探討的荷爾蒙物質。尿中FSH、estrogen及progesterone之代謝物以酵素連結免疫吸附分析法(enzyme-linked immunosorbent assay, ELISA)來分析。之後利用分析日誌中月經來潮的資料及尿液中荷爾蒙代謝物質的濃度,評估月經週期中濾泡期及黃體期的長短、月經週期是否排卵及荷爾蒙濃度的差異。

結果顯示,模組區的女性員工於濾泡前期,尿中促濾泡成熟激素及雌激素的代謝物濃度比起其他暴露組來得高。於線性迴歸分析中,相對於面板區,模組區的女性員工於早期濾泡期,尿中促濾泡成熟激素及雌激素的代謝物濃度較高(��:0.08, 95% CI: 0.00,0.16; ��:2.38, 95% CI: 0.25, 4.51)。由此結果推論,模組區女姓員工暴露於較高濃度多重化學物質,造成卵巢功能低落。因為卵巢功能低落,需要更多促濾泡成熟激素刺激濾泡成熟。而促濾泡成熟激素在濾泡前期主要刺激濾泡中細胞分泌雌激素,所以較高濃度的促濾泡成熟激素亦會帶動雌激素的上升。另外較高濃度的促濾泡成熟激素會造成濾泡期的縮短,而使得月經週期變短,與上一篇研究結果相呼應。而在此研究中並未發現模組區女性員工月經週期偏短的現象,可能是因為此研究為一自願性而非全面性的研究,而造成偏差及樣本數不足所導致。
1.The LCD-Display manufacturing is a rapid growing high-tech industry in Taiwan. It has become the second semiconductor manufacturing in Taiwan. The process of the LCD-Display manufacturing is involved array, panel and module. The array and panel process are similar to the semiconductor manufacturing process. In a study among semiconductor employees, the results indicate greater cycle length and higher cycle variability among women working in the thin film and ion implantation. Women working in the photolithography group had also a higher cycle variability and an elevated risk of short cycles. One study investigated in LCD manufacturing, no significant finding was observed among the exposed workers who handle ethylene glycol ethers (EGEEA) compared to a referent group of workers in the LCD manufacturing for duration of each menstrual cycle (period), duration (days) of the menses, and the amount of flow. Many chemical agents used in the process have been evaluated the female reproductive toxicity in animal studies. Knowledge about the reproductive toxicity of these agents in humans is scanty. There are many other potentially reproductive risk factors including electromagnetic field, shift work, and stress. Although studies investigated the effects of occupational exposures in LCD manufacturing were seldom.

The object of this cross-sectional study was to determine the effect of occupational exposures on menstrual cycle characteristics in LCD manufacturing. Menstrual function was estimated by questionnaire. Furthermore, we used handheld volatile organic compound (VOC) monitor and 24 hours canister sampling to assess potential chemical exposure. Electric and magnetic field exposure data were collected from an EMDEX meter. The study population consisted of female employees in a LCD plant in Taiwan. About 506 female workers age 19-60 years have completed routine health examination and the questionnaire during the end of 2002. For our analysis, 250 were excluded for the following criteria: above 40 years old; used oral contraceptives or other hormone; pregnancy or lactation; have had hysterectomy, bilateral oophorectomy, or other gynecologic surgery and smoking. Finally, the remaining 256 women were included in this analysis.

The results of 24 hours canister sampling analyzed showed that there were many chemical compounds had potentially reproductive effects especially in array and module areas. In addition, the results of handheld VOC monitor showed that there was higher concentration of total volatile organic compound in module area than others.

The data from the questionnaires was grouped by working areas:non-fabrication, array, panel, and module. Female worker in panel area(OR=2.34,95%CI= 1.00-5.49) and module area (OR=2.55,95%CI=1.10-5.91) have higher risk of menstrual length disorder than other groups. Female worker in module area (OR=4.79,95%CI=1.08-21.32) have higher risk of shorter menstrual length than other groups.

Therefore, we found an increased frequency of shorter menstrual cycles among the women working in module process. The conjecture of our study was that much higher concentration of potentially multiple chemicals exposure has substantial reproductive effects on the female workers in module area. Further, using daily urine metabolites of sex steroid hormones may allow us to obtain detailed menstrual function data and assess the potential reproductive effect of occupational exposure in this study site.


2.In our previous study, we found that Female worker in module area (OR=4.79,95%CI=1.08-21.32) have higher risk of shorter menstrual length than other groups. The possible explanation for these results was potential multiple chemical exposure such as ethanol, acetone, toluene, xylene, benzene, styrene, affect female reproductive system and lead to irregular menstrual cycle. In this study, using daily urine metabolites of sex steroid hormones may allow us to obtain detailed menstrual function data and assess the potential reproductive effect of occupational exposure in this study site.

Assays of prospectively collected daily urine samples for metabolites of reproductive endocrine such as follicle stimulating hormone (FSH), estrogens, and progesterone have been used in much epidemiologic studies to assess ovulatory status, timing of ovulation and menstrual function. Previous epidemiologic studies have examined the effects of phychological stress in work place, smoking, and occupation on menstrual function by using daily urinary hormone metabolites. In this study, we used this tool to estimate the length of segment, ovulatory status, and hormone levels. By the assessment, we could determine the target organs of the occupational exposure.

The objective of this cross-sectional study was to assess the potential reproductive endocrine effects of occupational exposure in the LCD manufacturing. Menstrual function was estimated by questionnaire. Reproductive endocrine was evaluated by detecting the concentration of reproductive hormonal metabolites in urine, either questionnaire or daily diary. Furthermore, we used handheld volatile organic compound (VOC) monitor and 24 hours canister sampling to assess potential chemical exposure. Electric and magnetic field exposure data were collected from an EMDEX meter.

The study population consisted of female employees in a LCD plant in Taiwan. About 256 female workers have completed the questionnaire during the end of 2003. They were screened by a face-to-face interview to identify those who were eligible and willing to collect and freeze urine samples daily after waking for up to 1.5 menstrual cycles. Finally, urine samples of 96 subjects were included in urinary hormone analysis. Participants completed a detailed baseline questionnaire. We assayed FSH, E1C (estrone conjugates) and PdG (Pregnanediol-3-glucuronide) by ELISA. We also obtained reproductive and exposure information from baseline questionnaire and daily diary.

After adjusting effects of factors on hormonal excretion, E1C level of the female workers in module group still had a significantly increased (2.38 ng/mg Cr, 95% CI: 0.25, 4.51) compared with the female workers in panel group in early follicular phase. FSH level of the women in module group had a little significantly increased (0.08 mIU/mg Cr, 95% CI: 0.00,0.16) adjusted by effects compared with the women in panel group in early follicular phase.

The possibility is that multiple chemical exposures may diminish ovarian oocyte reserve or induced ovarian failure. Furthermore, shorten follicular phase may lead to shorten menstrual cycle. It is consistent with the finding of our previous study.
1.
摘要 1
Abstract 3
Introduction 7
Material and Methods 8
Study Population 8
Exposure Assessment 8
The questionnaire 9
Statistical analysis 10
Results 11
Results of exposure assessment 11
Results of data analysis 11
Discussion 18
References 21


2.
摘要 1
Abstract 3
Introduction 6
Material and Methods 7
Research Design and Population 7
Initial Participant Interview and Questionnaire 8
Exposures Assessment 9
Urine samples collection 9
Determination of menstrual endpoints and phase characteristics 10
Endocrine measurements 11
Statistical analysis 12
Results 13
Results of exposure assessment 13
Results of hormone assay 14
Discussion 23
References 27
Appendix 1. Flowchart of LCD manufacturing process 30
Appendix 2. 員工健康檢查問卷調查表 33
Appendix 3. Daily Dairy 41
Appendix 4. Air sampling levels (ppb) of volatile organic compound by administrative department and three areas in fabrication 43
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