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系統識別號 U0026-0812200914105730
論文名稱(中文) 暴露於多氯聯苯與多氯呋喃對女性內分泌與生殖功能之研究
論文名稱(英文) Female endocrine and reproductive function associated with PCBs/PCDFs exposure
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 96
學期 2
出版年 97
研究生(中文) 楊秋月
研究生(英文) Chiu-yueh Yang
學號 S5889117
學位類別 博士
語文別 中文
論文頁數 101頁
口試委員 口試委員-王應然
召集委員-蔡少正
口試委員-郭浩然
口試委員-陳保中
口試委員-林銘德
指導教授-郭育良
中文關鍵字 多氯聯苯  初經  月經  受孕等待時間  動情激素  多氯呋喃 
英文關鍵字 PCDFs  estradiol  menarche  PCBs  menstruation  infereility  TTP 
學科別分類
中文摘要 在動物實驗中多氯聯苯與多氯呋喃,會對內分泌系統及雌性生殖系統造成影響。但在人類研究中,暴露多氯聯苯與多氯呋喃這些物質所造成的生殖危害尚未十分清楚。因此本研究即針對台灣中部一群因食用多氯聯苯及呋喃污染之米糠油中毒之油症世代進行調查,以期瞭解多氯聯苯與多氯呋喃暴露與女性生殖危害之相關性。

我們邀請全部多氯聯苯與多氯呋喃中毒事件油症婦女及其配對之參考組婦女,進行電話問卷調查,收集女性月經特質及懷孕等待時間之資料,另我們也邀請油症中毒女性所生之女兒及其配對之參考組,於青春期時參加研究,填寫84天之月經日記及於月經來潮之第3天,抽血分析相關之賀爾蒙濃度。

本研究結果分為三部分:
第一 對於油症第二代少女,多氯聯苯與多氯呋喃暴露會導致較短的月經週期及月經流血天數,另多氯聯苯與多氯呋喃暴露會增加血清中動情激素濃度。
第二 根據412位已婚油症婦女及其配對之參考組資料顯示,多氯聯苯與多氯呋喃暴露延長受孕等待時間,如將受孕等待時間超過12月定義為不孕症,則發現多氯聯苯與多氯呋喃暴露會增加不孕症之危險性。
第三 從423位油症婦女及其配對之參考組的月經特質資料顯示,多氯聯苯與多氯呋喃暴露會縮短月經週期,且中毒者如有皮膚病變其月經週期會更短,其次,月經流血天數,暴露組較長,多氯聯苯與多氯呋喃暴露與月經週期之相關性於青春期前中毒者較為明顯。另多氯聯苯與多氯呋喃暴露與初經未發現有相關性。

總結以上結果,多氯聯苯/呋喃類的暴露會改變女性內分泌及增加生殖危害,其致病機轉尚未清楚,因此,有待更進一步研究探討。
英文摘要 Polychlorinated biphenyls (PCBs) and related compounds such as polychlorinated dibenzofurans (PCDFs) alter endocrine and the female reproductive system in animals. In 1978-1979, a mass poisoning occurred in central Taiwan from cooking oil contaminated by PCBs/PCDFs. The purposes of our study were to investigate the relationship of PCBs/PCDFs exposure with endocrine and reproductive function in women.

We invited Yucheng girls age 13-19 years, born to mothers exposure to PCBs/PCDFs, and Yucheng women age less 20 years in 1979. We conducted a telephone survey with Yucheng women to collect menstrual characteristics and time to pregnancy. Yucheng girls recorded their menstrual characteristics daily for 84 days and serum levels of estradiol, LH, FSH and testosterone were measured on the third day of menstruation.

The results included three parts. First, A total of 17 exposed girls and controls participated, the exposed girls reported shorter mean duration of bleeding per cycle than 16 unexposed (5.5 vs 6.5 days, P=0.0055). Serum level of estradiol (p=0.016) was higher in exposed girls as compared to reference. Second, totally 412 women responded satisfactorily, with median TTP 4 months in Yucheng and 3 months in reference women (p=0.019). After adjusting for confounders by Cox regression, Yucheng women had fecundability ration of 0.90 (95 % confidence interval (CI): 0.80, 1.00). Among the 408 women who had non-contraceptive sexual activity for more than 12 months, 19.7% Yucheng women and 9.7% reference did not become pregnant (i.e., infertile). After adjusting confounders by logistic regression, the infertility odds ratio was 2.34, (95 % CI: 1.23, 4.59) for Yucheng women as compared to reference. Third, totally 423 women responded satisfactorily for analyses menstrual cycle length. Yucheng women on average 0.24 (95% CI: 0.03, 0.89) days shorter than the menstrual cycles of the reference group. Increasing the severity levels of skin lesions was associated with decreasing cycle length, with a difference of 1.1(95% CI: 0.28, 1.91) days in the most severity levels, such as the Yucheng with skin lesions, compared to reference (p for trend test =0.03). In addition, the Yucheng women when they exposed PCBs/PCDFs at premenacheal period were significant longer days of menstrual flow (adjusted =0.26 day, 95% CI: 0.01, 0.51). On the other hand, there were no association between PCBs/PCDFs exposure and age at menarche.

We conclude that prenatal exposure to PCBs/PCDFs resulted in abnormal menstruation and higher estradiol and FSH levels in follicular phase of menstrual cycle in adolescent girls. However, There were the association between PCBs/PCDFs and female reproductive hazards. The mechanisms are still unknown and warranted to be further investigated.
論文目次 目 錄

中文摘要 ………………………………………………………………… I
Abstract …………………………………………………………………… III
誌謝 ……………………………………………………………………… V
目錄 ……………………………………………………………………… VI
表目錄……………………………………………………………………… VIII
圖目錄……………………………………………………………………… IX
縮寫對照……………………………………………………………………… X
第一章 緒論……………………………………………………………… 1
1.1 前言……………………………………………………………… 1
1.2 女性生殖系統…………………………………………………… 1
1.3 多氯聯苯………………………………………………………… 5
1.4 多氯呋喃/多氯戴奧辛 ………………………………………… 9
1.5 多氯聯苯/多氯呋喃/多氯戴奧辛之毒性作用 ………… 10
1.6 多氯聯苯的雌性生殖功能影響-動物實驗 …………………… 13
1.7 多氯聯苯的人類流行病學研究………………………………… 13
1.8 論文研究假說 ………………………………………………… 31
第二章 研究對象與方法………………………………………………… 34
2.1 出生前暴露多氯聯苯與多氯呋喃對青少女內分泌及生殖功能之影響………………………………………………………………… 34
2.2 多氯聯苯與多氯呋喃暴露導致油症婦女受孕等待時間延長… 38
2.3 多氯聯苯與多氯呋喃暴露對女性月經特質之影響 ………… 46
第三章 結果…………………………………………………………… 52
3.1 油症中毒世代之第一代女性的基本資料 …………………… 52
3.2 油症中毒世代之第二代女性的基本資料 …………………… 53
3.3 血清性荷爾蒙濃度 …………………………………………… 54
3.4 生育能力 ……………………………………………………… 54
3.5 月經週期 ……………………………………………………… 55
3.6 不同階段暴露多氯聯苯與多氯呋喃對月經特質的影響 …… 57
第四章 討論 …………………………………………………………… 60
4.1 本研究重要性及獨特性 ……………………………………… 60
4.2 出生前暴露多氯聯苯與多氯呋喃對油症少女內分泌之影響… 61
4.3 多氯聯苯與多氯呋喃暴露導致油症婦女受孕等待時間延長… 63
4.4 多氯聯苯與多氯呋喃暴露對女性初經來潮之影響………… 65
4.5 多氯聯苯與多氯呋喃暴露對女性月經週期之影響………… 66
4.6 未來之研究方向……………………………………………… 67
第五章 結論…………………………………………………………… 69
參考文獻………………………………………………………………… 82
附錄一 臺灣地區居民健康調查問卷………………………………… 92
附錄二 與本研究相關之發表…………………………………………… 101

表目錄

表1 歷年來,台灣油症患者血液中多氯聯苯及呋喃之平均含量 19
表2 歷年來,個案血中濃度之含量最多的6個PCB同源物及2個主要PCDF濃度值…………………………………………………… 21
Table 3. Background characteristics of Yucheng women cohort and their reference group as of 2003……………………………………… 70
Table 4. Background characteristics of studied Yucheng and reference women, 2003…………………………………………………… 71
Table 5. Characteristic and medical history of female Yucheng and unexposed adolescents………………………………………… 72
Table 6. Serum hormonal levels in menstruation period of Yucheng and unexposed girls………………………………………………… 73
Table 7. Fecundability ratios (FR) with 95% CI between reference and Yucheng women, and among 1980-2 serum PCBs level groups 74
Table 8. The crude and adjusted odds ratios for infertility due to exposure group, age of woman and husband at first pregnancy, and frequency of intercourse before first pregnancy in 408 women………………………………………………………… 75
Table 9. Menstrual cycle irregularity and dysmenorrhea among Yucheng and reference women…………………………………………… 76
Table 10. Menstrual cycle length and days of menstrual flow among Yucheng and reference women………………………………… 77
Table 11. Menstruation and reproductive function of female Yucheng and unexposed adolescents………………………………………… 78
Table 12. Menstruation characteristics by girls’ daily records for 84 days 79
Table 13. Age of menarche (mean ± SD) in 113 women who were younger than 10 year of age and premenarcheal in 1979……… 80



圖目錄

圖1 女性月經週期中生殖系統之變化……………………………… 4
圖2 戴奧辛類化學物質之基本結構………………………………… 7
圖3 戴奧辛類化學物質可能的毒性致病機轉……………………… 12
圖4 台灣油症事件發生的主要鄉鎮地區及罹病率(每百萬人)分佈 16
圖5 義大利Seveso中毒事件之分部區域……………………… 27
圖6 油症少女研究架構圖…………………………………………… 34
圖7 油症婦女研究架構圖…………………………………………… 38
圖8 第一代油症中毒婦女施測生殖問卷之收案流程……………… 40
圖9 第一代油症中毒婦女施測月經特質問卷之收案流程………… 47
圖10 油症婦女與參考組受孕等待時間之分佈……………………… 81
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