Susanne Lund Kristensen1, Cecilia Høst Ramlau-Hansen2, Erik Ernst3, Sjurdur Frodi Olsen4, Jens Peter Bonde5, Anne Vested6, Thorhallur Ingi Halldorsson7, Panu Rantakokko8, Hannu Kiviranta8, Gunnar Toft9. 1. Danish Ramazzini Centre, Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Obstetrics and Gynecology, Regional Hospital of Randers, Denmark. Electronic address: susankst@rm.dk. 2. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. 3. Department of Gynaecology and Obstetrics, Aarhus University Hospital, and Institute of Anatomy, University of Aarhus, Aarhus, Denmark. 4. Centre for Fetal Programming, Statens Serum Institut, Copenhagen, Denmark. 5. Department of Occupational and Environmental Medicine, Bispebjerg Hospital of Copenhagen University, Copenhagen, Denmark. 6. Danish Ramazzini Centre, Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. 7. Centre for Fetal Programming, Statens Serum Institut, Copenhagen, Denmark; Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 8. National Institute for Health and Welfare, Department of Environmental Health, Chemical Exposure Unit, Kuopio, Finland. 9. Danish Ramazzini Centre, Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND: The biopersistent organochlorine pollutants dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) can be detected in humans worldwide. The chemicals can cross the placenta and may interfere with endogenous hormonal homeostasis. OBJECTIVES: To investigate effects on female reproduction following intrauterine exposure to selected biopersistent organochlorines. METHODS: We used data from a Danish pregnancy cohort with follow-up on 436 eligible daughters at approximately 20years of age. Information on age of menarche (n=335), menstrual cycle length (n=230) and serum concentrations of reproductive hormones (n=243) was obtained. Number of antral follicles was counted by vaginal ultrasound (n=147). Of 244 daughters who attended clinical examination, 170 used hormonal contraceptives and 74 were non-users. Concentrations of p,p'-DDE, HCB and six PCB congeners were analysed in maternal serum samples obtained in pregnancy week 30. RESULTS: Age of menarche and menstrual cycle length were found not to be statistically significant associated with prenatal organochlorine exposure. Among non-users of hormonal contraceptives with information on antral follicle number (n=43), daughters exposed to the highest tertile of p,p'-DDE had 28% (95% confidence interval (95% CI): 5; 46%) lower follicle number compared to the low-level exposed reference group. Those exposed to medium and higher levels of HCB had 30% (95% CI: 5; 48%) and 28% (95% CI: 7; 44%) lower follicle number compared to the reference group. Furthermore, maternal serum HCB concentrations were inversely associated with free androgen index among non-users of hormonal contraceptives (n=73). These associations were not found in users of hormonal contraceptives. CONCLUSIONS: Among non-users of hormonal contraceptives, we found indications of adverse long-term effects on female reproduction following prenatal exposure to biopersistent organochlorines. These findings may have wide implications for public health as intrauterine exposure occurs worldwide.
BACKGROUND: The biopersistent organochlorine pollutants dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) can be detected in humans worldwide. The chemicals can cross the placenta and may interfere with endogenous hormonal homeostasis. OBJECTIVES: To investigate effects on female reproduction following intrauterine exposure to selected biopersistent organochlorines. METHODS: We used data from a Danish pregnancy cohort with follow-up on 436 eligible daughters at approximately 20years of age. Information on age of menarche (n=335), menstrual cycle length (n=230) and serum concentrations of reproductive hormones (n=243) was obtained. Number of antral follicles was counted by vaginal ultrasound (n=147). Of 244 daughters who attended clinical examination, 170 used hormonal contraceptives and 74 were non-users. Concentrations of p,p'-DDE, HCB and six PCB congeners were analysed in maternal serum samples obtained in pregnancy week 30. RESULTS: Age of menarche and menstrual cycle length were found not to be statistically significant associated with prenatal organochlorine exposure. Among non-users of hormonal contraceptives with information on antral follicle number (n=43), daughters exposed to the highest tertile of p,p'-DDE had 28% (95% confidence interval (95% CI): 5; 46%) lower follicle number compared to the low-level exposed reference group. Those exposed to medium and higher levels of HCB had 30% (95% CI: 5; 48%) and 28% (95% CI: 7; 44%) lower follicle number compared to the reference group. Furthermore, maternal serum HCB concentrations were inversely associated with free androgen index among non-users of hormonal contraceptives (n=73). These associations were not found in users of hormonal contraceptives. CONCLUSIONS: Among non-users of hormonal contraceptives, we found indications of adverse long-term effects on female reproduction following prenatal exposure to biopersistent organochlorines. These findings may have wide implications for public health as intrauterine exposure occurs worldwide.
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