Anne Marie L Thomsen1, Anders H Riis1, Jørn Olsen1, Bo A G Jönsson2, Christian H Lindh2, Niels H Hjollund1,3, Tina Kold Jensen4, Jens Peter Bonde5, Gunnar Toft6. 1. Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark. 2. Division of Occupational and Environmental Medicine, Lund University Hospital, SE 221 85 Lund, Sweden. 3. Department of Occupational Medicine, Herning Regional Hospital, DK-7400 Herning, Denmark. 4. Department of Environmental Medicine, University of Southern Denmark, DK-5000 Odense, Denmark. 5. Department of Occupational and Environmental Medicine, Copenhagen University Hospital Bispebjerg-Frederiksberg, DK-2400 Copenhagen NW, Denmark. 6. Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark gunnar.toft@clin.au.dk.
Abstract
STUDY QUESTION: Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER: Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP. WHAT IS KNOWN ALREADY: Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction. STUDY DESIGN SIZE AND DURATION: A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS: We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE: Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP. LIMITATIONS REASONS FOR CAUTION: Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products. STUDY FUNDING/COMPETING INTERESTS: The original data collected were founded by Aarhus University Research Foundation, the Danish Medical Research Council and the Danish Medical Health Insurance Foundation. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER: N/A.
STUDY QUESTION: Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER: Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP. WHAT IS KNOWN ALREADY: Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction. STUDY DESIGN SIZE AND DURATION: A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS: We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE: Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP. LIMITATIONS REASONS FOR CAUTION: Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products. STUDY FUNDING/COMPETING INTERESTS: The original data collected were founded by Aarhus University Research Foundation, the Danish Medical Research Council and the Danish Medical Health Insurance Foundation. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER: N/A.
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