多氯聯苯、多氯夫喃和多氯戴奧辛均為重要的環境污染物。由動物實驗中發現這些環境中的「內分泌干擾物質」會改變動物的性徵發育及內分泌功能。然而在人類，尚未有可信的有關此類物質引起生殖系統功能異常之完整研究或報告。因此透過本研究，我們可藉以評估多氯聯苯/夫喃對女性中毒者之生殖效應。

　　在1979年間台灣中部發生了因食用被多氯聯苯/夫喃污染的米糠油而受害的大規模中毒事件，此事件被稱為油症。為評估中毒者之第一代女性生殖機能，將針對中毒者的第一代女性與其經性別、年齡、種族、居住地區、教育程度配對過的對照組進行「回溯性生育能力之研究」，利用問卷以瞭解其經期特徵、懷孕之相關疾病及受孕所需時間(time to pregnancy)等生殖系統相關問題。

　　共有192位中毒者及188位對照者完成問卷調查，其中青春期前就暴露於多氯聯苯/夫喃的中毒者較對照者之平均月經來潮天數有顯著性延長(5.8 vs. 5.3, p=0.02)，而平均月經週期也有較長的現象(30.4 vs. 29.8)。已婚婦女中，135位中毒者與132位對照者相較下，早產比例增加(16.8% vs. 9.3%)，死產的比例也增加(6.1% vs. 2.3%)；青春期前就暴露的中毒者較對照者之死產比例呈顯著差異(6.4% vs. 0%, p=0.05 )； 暴露濃度高、中及對照組相較下，死產比例也呈顯著差異(13.5% vs. 1.9% vs.2.3%, p=0.003)。以受孕所需時間（TTP）作為生育力指標時，中毒者較對照者之受孕比顯著下降(fecundability ratio=0.85, 95%CI:0.73~0.98)。

　　因此，本研究發現多氯聯苯/夫喃對女性月經功能、懷孕結果及生育力都會造成影響。

　　Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-furans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) are among the most widespread environment pollutants. These endocrine disrupting chemicals alter sexual maturation and endocrine function in animal studies, but their effects on humans’ reproductive system are not well studied. The purpose of this study was to assess reproductive effects in women exposed to PCBs/PCDFs.

　　In Taiwan in 1979, a severe event of accidental exposure to PCBs/PCDFs due to ingestion of PCBs/PCDFs-contaminated rice-bran oil was reported and called Yucheng (oil-disease). Information on menstrual characteristics, reproductive function, and reproductive history including time to pregnancy were collected retrospectively by a questionnaire interview.

　　A total of 192 Yucheng women and 188 controls matched for sex, age, gender, area of residence and educational level completed the questionnaire interview satisfactorily. Yucheng women exposed to PCBs/PCDFs before puberty had longer days of menstrual flow (5.8 vs. 5.3, p=0.02) and mean menstrual cycle length (30.4 vs. 29.8). Among 135 married Yucheng women and 132 controls, more of the Yucheng women reported having premature birth rate (16.8% vs. 9.3%) and stillbirth rate (57.1% vs. 44.4%). Yucheng women exposed to PCBs/PCDFs before puberty had higher stillbirth rate (6.4% vs. 0%, p=0.05). High level PCBs/PCDFs exposure also had a higher stillbirth rate (13.5% vs. 1.9% vs.2.3%, p=0.003). Waiting time to pregnancy of Yucheng women was longer than controls, and a decrease fecundability ratio was found (fecundability ratio=0.85, 95%CI: 0.73~0.98).

　　Our findings suggest that women exposed to PCBs/PCDFs were affected their reproductive function.

Allen J, Barsotti D, Lambrecht L, et al. Reproductive effects of halogenated aromatic hydrocarbons on nonhuman primates. Ann N Y Acad Sci 1979; 320:419–25.

Axmon A, Rylander L, Stromberg U, et al. Time to pregnancy and infertility among women with a high intake of fish contaminated with persistent organochlorine compounds. Sand J Work Environ Health 2000; 26:199-206.

Axmon A, Rylander L, Stromberg U. Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in relation to time to pregnancy. J Toxicol Environ Health 2001; 64:485-98.

Barid DD, Wilcox AJ, Weinberg CR. Use of time to pregnancy to study environmental exposures. Am J Epedemiol 1986; 124:470-80.

Barsotti DA, Marlar RJ, Allen JR. Reproductive dysfunction in rhesus monkeys exposed to low levels of polychlorinated biphenyls (Aoroclor 1248). Food Cosmet Toxicol 1976; 14:99-103.

Barsotti DA, Van Miller JP. Accumulation of a commercial polychlorinated biphenyl mixture (Aroclor 1016) in adult rhesus monkeys and their nursing infants. Toxicology 1984; 30:31-44.

Bracken MB, Hellenbrand KG, Holford TR. Conception delay after oral contraceptive use: the effect of estrogen dose. Fertil Steril 1990; 53:21-7.

Buck GM, Sever LE, Mendola P, et al. Consumption of contaminated sport fish from Lake Ontario and time-to-pregnancy. Am J Epidemiol 1997; 146:949-54.

Buck GM, Mendola P, Vena JE, et al. Paternal Lake Ontario fish consumption and risk of conception delay, New York State Angler Cohort. Environ Res 1999; 80:S13-S18.

Buck GM, Vena JE, Schisterman EF, et al. Parental consumption of cotaminated sport fish from Lake Ontario and predicted fecumdability. Epidemiol 2000; 11:388-93.

Centers for Disease Control. Preliminary Report: dioxin levels of exposed population in Seveso, Italy. JAMA 1990,263:1023-5

Chen HS. Polychlorinated Biphenyls: Environmental occurrence, biological and toxicological effects. Cli Med (Taipei) 1981; 7:4-8.

Chen PC, Hsieh GY, Wang JD, et al. Prolonged time to pregnancy in female workers ezposed to ethylene glycol ethers in semiconductor manufacturing. Epidemiol 2002; 13:191-6.

Chen PH, Luo ML, Wong CK, et al. Polychlorinated biphenyls, dibenzofurans, and quaterphenyls in the toxic rice-bran oil and PCBs in the blood of patients with PCB poisoning in Taiwan. Prog Cli Biol Res 1984; 137:133-45.

Colborn T, vom Saal FS, Soto AM. Developmental effects of endocrine disrupting chemicals in wildlife and humans. Environ Health Persp 1993; 101:378-84.

Cook JC, Caido KW, Greenlee WF. Ah receptor: Relevance of mechanistic studies to human risk assessment. Environ Health Perspect 1987; 76:71-7.

Cordle F, Cornelissen P, Jelinek C, et al. Human exposure to polychlorinated biphenyls and polybrominated biphenyls. Environ Health Persp 1978; 24:157-74.

del Rio Gomez I, Marshall T, Tsai P, et al. Number of boys born to men exposed to polychlorinated biphenyls. Lancet 2002; 360:143-4.

Eskenazi B, Mocarelli P, Warner M, et al. Seveso women’s health study: a strsy of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive health. Chmosphere 2000; 40:1247-53.

Eskenazi B, Warner M, Mocarelli P, et al. Serum dioxin concentrations and menstrual cycle characteristics. Am J Epidemiol 2002; 156:383-91.

Eskenazi B, Mocarelli P, Warner M, et al. Serum dioxin concentrations and endometriosis: A cohort strdy in Seveso, Italy. Environ Health Persp 2002; 110:629-34.

Fady I, Sharara MD, Seifer MD, et al. Environmental toxicants and female reproduction. Fertil Steril 1998; 70:613-22.

Flesch-Janys D, Steindorf K, Gurn P, et al. Estimation of the cumulated exposure to polychlorinated dibenzo-p-dioxins/furans and standardized mortality ratio analysis of cancer mortality by dose in an occupationally exposed cohort. Enviro Health Persp 1998; 106:655-62.

Guo YL, Ryan JJ, Lau BPY, et al. Blood Serum Levels of PCBs and PCDFs in Yucheng Women 14 Years After Exposure to a Toxic Rice Oil. Arch Environ Contam Toxicol 1997; 33:104-8.

Guo YL, Hsu PC, Hsu CC,et al. Semen quality after prenatal exposure to polychlorinated biphenyls and dibenzofurans. Lancet 2000; 356:1240-1.

Harlow SD, Ephross SA. Epidemiology of menstruation and its relevance to women’s health. Epidemiol Rev 1995; 17:265-86.

Hayabuchi H, Yoshimura T, Kuratsune M. Consumption of toxic rice oil by 'yusho' patients and its relation to the clinical response and latent period. Food Cosmet Toxicol 1979; 17:455-61.

Hsu ST, Ma CI, Hsu SK, et al. Discovery and epidemiology of PCB poisoning in Taiwan. Am J Ind Med 1984; 5:71-9.

Hsu ST, Ma CI, Hsu SK, et al. Discovery and epidemiology of PCB poisoning in Taiwan: a four-year followup. Environ Health Persp 1985; 59:5-10.

James RC, Busch H, Tamburro CH, et al. Polychlorinated biphenyl exposure and human disease. J Occup Med 1993; 35:136-48.

Jensen TK, Scheike T, Keiding N, et al. Fecundability in relation to body mass and menstrual cycle patterns. Epidemiol 1998; 10:422-8.

Joffe M, Villard L, Li Z, et al. A time to pregnancy questionnaire designed for long term recall: validity in Oxford, England. J Epidemiol Community Health 1995; 49:314-9.

Joffe M. Decreased fertility in Britain compared with Finland. Lancet 1996; 347 :1519-22.

Kimbrough RD. Polychlorinated biphenyls (PCBs) and human health: an update. Crit Rev Toxicol 1995; 25:133-63.

Koga N, Kikuichi N, Kanamaru T, et al. Hamster liver cytochrome P450 (CYP2A8) as a 4-hydroxylase for 2,5,2',5'-tetrachlorobiphenyl. Biochem Bioph Res Co 1996; 225:685-8.

Kogevinas M. Human health effects of dioxins: cancer, reproductive and endocrine system effects. Hum Reroduct Update 2001; 7:331-9.

Kusuda M. Yusho and female: studies on sexual functions in female patients with rice oil poisoning. Sanda to Fujinka 1971; 38:1063-72

Landers JP, Bunce NJ. The Ah receptor and the mechanism of dioxin toxicity. Biochem J 1991; 276:273-87.

Lang V. Polychlorinated biphenyls in the environment. J Chromat 1992; 595:1-43.

Lindbohm, ML. Women’s reproductive health: Some recent developments in occupational epidemiology. Am J Ind Med 1999; 36:18-24.

Longnecker MP, Rogan WJ, Lucier G. The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health. Ann Rev Public Health 1997; 18:211-44.

Manz A, Berger J, Dwyer JH, et al. Cancer mortality among workers in chemical plant contaminated with dioxin [see comments]. Lancet 1991; 338:959-64.

Masuda Y. Health status of Japanese and Taiwanese after exposure to contaminated rice oil. Environ Health Perspect 1985,60:321-5.

May G. Chloracne from the accidental production of tetrachlorodibenzo-dioxin. Brit J Ind Med 1982; 39:128-35.

McConnell R, Anderson K, Russell W, et al. Angiosarcoma, porphyria cutanea tarda, and probable chloracne in a worker exposed to waste oil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Brit Indust Med 1993; 50:699-703.

Mcguinness BM, Buck GM, Mendola P, et al. Infecundity and consumption of polychlorinated biphenyl-contaminated fish. Arch Environ Health 2001; 56:250-3.

Mendola P, Buck GM, Vena JE, et al. Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death. Environ Health Perp 1995; 103:498-502.

Mendola P, Buck GM, Sever LE, Zielezny M, Vena JE. Consumption of PCB-contaminated freshwater fish and shortened menstrual cycle length. Am J Epidemiol 1997; 146:955-60.

Mocarelli P, Marocchi A, Brambilla P, et al. Clinical laboratory manifestations of exposure to dioxin in children. A six-year study of the effects of an environmental disaster near Seveso, Italy. JAMA 1986; 256:2687-95.

Mocarelli P, Brambilla P, Gerthoux PM, et al. Chang in sex ratio with exposure to dioxin. Lancet 1996; 348:409.

Mocarelli P, Gerthoux PM, FerrarI E, et al. Paternal concentrations of dioxin and sex ratio of offspring. Lancet 2000; 355:1858-63.

Morita M, Nakagawa J, Rappe, C. Polychlorinated dibenzofuran (PCDF) formation from PCB mixture by heat and oxygen. Bull Enviro Contam Toxicol 1978; 19:665-70.

Moses M, Prioleau PG. Cutaneous histologic findings in chemical workers with and without chloracne with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Am Acad Dermatol 1985; 12:497-506.

Olsen J, Andersen PK. We should monitor human fecundity, but how? A suggestion for a new method that may also be used. Epidemiol 1999; 10:419-21.

Rogan WJ, Giaden BC, Guo YL, et al. Sex ratio after exposure to dioxin-like chemicals in Tiawan. Lancet 1999; 16:206-7.

Ryan JJ, Levesque D, Panopio LG, et al. Elimination of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) from human blood in the Yusho and Yu-Cheng rice oil poisonings. Arch Environ Contam Toxicol 1993; 24:504-12.

Safe S. Determination of 2,3,7,8-TCDD toxic equivalent factors TEF: Support for the use of the in vitro AHH induction assay. Chemosphere 1987; 16:791-802.

Safe, S. Modulation of gene expression and endocrine response pathways by 2’,3’,7’,8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol Therap 1995; 67:247-81.

Wang WJ, Shen RL, To CL. Investigation on severe PCB poisoning in-patients. Cli Med (Taipei) 1981; 7: 62-5.

Yoshimura T, Kaneko S, Hayabuchi H. Sex ratio in offsping of those affected by doxin and dioxin-like compounds: The Yusho, Seveso, and Yucheng incidents. Occup Environ Med 2001; 58:540-1.

Yu ML, Guo YL, Hsu CC, et al. Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: Long-term follow-up interviews of the women from the Taiwan Yucheng cohort. Int J Epidemiol 2000; 29:672-7.

中時晚報，”多氯聯苯餘毒未消”，第五版，1996年12月2日。

自由時報，”多氯聯苯中毒18年後討公道”，第九版，1996年12月3日。

許世昌，”最新實用解剖生理學”，582-630頁，1993年。

郭育良等，“職業病概論”，655-70頁，二版2002。

陳錫松："多氯聯苯-環境中的存在、生物及毒性效應"，臨床醫學1981，7：4-8。

黃文郁。台灣地區婦女生育力參考曲線之建立（碩士論文）。台北：國立台灣大學公共衛生學院職業醫學與工業衛生研究所，1999。

張火炎、李俊璋、桂椿雄、郭育良等："多氯戴奧辛類化學物質之暴露與毒性"，中華衛誌1999；18：13-27。

葛應欽、張正二、劉尚修："多氯連苯中毒患者之流行病學研究"，台灣醫誌1980；79：856。

葛應欽、饒連財、許書刀等："多氯聯苯在中毒患者之血中濃度"，台灣醫誌1981；80：774-9。

藍忠孚、陳錫松、謝玲玲、陳運紅："台中地區多氯聯苯中毒之流行病學研究"，臨床醫學1981；7：96-100。