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      Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss

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          Abstract

          Background

          Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss.

          Objectives

          We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy.

          Methods

          Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss.

          Results

          Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: –0.5 days (95% CI: –0.9, –0.1), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: –0.8 days (95% CI: –1.2, –0.4), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.02), p = 0.001].

          Conclusions

          BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle–specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies.

          Citation

          Jukic AM, Calafat AM, McConnaughey DR, Longnecker MP, Hoppin JA, Weinberg CR, Wilcox AJ, Baird DD. 2016. Urinary concentrations of phthalate metabolites and bisphenol A and associations with follicular-phase length, luteal-phase length, fecundability, and early pregnancy loss. Environ Health Perspect 124:321–328;  http://dx.doi.org/10.1289/ehp.1408164

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          Phthalates and human health.

          R. Hauser, A M Calafat (2005)
          Article 0 comments Cited 220 times – based on 0 reviews     Review now
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            Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby.

            Allen Wilcox, Clarice R. Weinberg, Donna Baird (1995)
            The timing of sexual intercourse in relation to ovulation strongly influences the chance of conception, although the actual number of fertile days in a woman's menstrual cycle is uncertain. The timing of intercourse may also be associated with the sex of the baby. We recruited 221 healthy women who were planning to become pregnant. At the same time the women stopped using birth-control methods, they began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. We measured estrogen and progesterone metabolites in urine to estimate the day of ovulation. In a total of 625 menstrual cycles for which the dates of ovulation could be estimated, 192 pregnancies were initiated, as indicated by increases in the urinary concentration of human chorionic gonadotropin around the expected time of implantation. Two thirds (n = 129) ended in live births. Conception occurred only when intercourse took place during a six-day period that ended on the estimated day of ovulation. The probability of conception ranged from 0.10 when intercourse occurred five days before ovulation to 0.33 when it occurred on the day of ovulation itself. There was no evident relation between the age of sperm and the viability of the conceptus, although only 6 percent of the pregnancies could be firmly attributed to sperm that were three or more days old. Cycles producing male and female babies had similar patterns of intercourse in relation to ovulation. Among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation. For practical purposes, the timing of sexual intercourse in relation to ovulation has no influence on the sex of the baby.
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              Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010

              Ami R. Zota, Antonia M Calafat, Tracey J. Woodruff (2014)
              Background: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures. Objective: We examined temporal trends in urinary concentrations of phthalate metabolites in the general U.S. population and whether trends vary by sociodemographic characteristics. Methods: We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001–2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models. Results: LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and ΣDEHP metabolites decreased between 2001–2002 and 2009–2010 [percent change (95% CI): –42% (–49, –34); –17% (–23, –9); –32% (–39, –23) and –37% (–46, –26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of ΣDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (p interaction < 0.01). Conclusions: Exposure of the U.S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends. Citation: Zota AZ, Calafat AM, Woodruff TJ. 2014. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001–2010. Environ Health Perspect 122:235–241; http://dx.doi.org/10.1289/ehp.1306681
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                Author and article information

                Journal
                Journal ID (nlm-ta): Environ Health Perspect
                Journal ID (iso-abbrev): Environ. Health Perspect
                Journal ID (publisher-id): EHP
                Title: Environmental Health Perspectives
                Publisher: National Institute of Environmental Health Sciences
                ISSN (Print): 0091-6765
                ISSN (Electronic): 1552-9924
                Publication date (Electronic): 10 July 2015
                Publication date (Print): March 2016
                Volume: 124
                Issue: 3
                Pages: 321-328
                Affiliations
                [1 ]Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Durham, North Carolina, USA
                [2 ]Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
                [3 ]Westat, Durham, North Carolina, USA
                [4 ]Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA
                [5 ]Biostatistics Branch, NIEHS, NIH, DHHS, Durham, North Carolina, USA
                Author notes
                [† ]Address correspondence to A.M. Jukic, Epidemiology Branch, NIEHS, P.O. BOX 12233, Durham, NC 27709 USA. Telephone: (919) 541-2992. E-mail: jukica@ 123456niehs.nih.gov
                [*]

                Current address: Yale Center for Perinatal, Pediatric and Environmental Epidemiology, One Church St, 6th Floor, New Haven, CT 06510 USA. Telephone: (203) 764-9382; E-mail: Annemarie.jukic@ 123456yale.edu

                Article
                Publisher ID: ehp.1408164
                DOI: 10.1289/ehp.1408164
                PMC ID: 4786975
                PubMed ID: 26161573
                SO-VID: bf00cf79-fe5b-4174-8e8d-217573f3a317
                License:

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                Date received : 22 January 2014
                Date accepted : 07 July 2015
                Date: 10 July 2015
                Date: 01 March 2016
                Categories
                Subject: Research

                ScienceOpen disciplines: Public health
                Data availability:
                ScienceOpen disciplines: Public health

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