Fact checked byRichard Smith

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January 08, 2024
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Exposure to endocrine-disrupting chemicals may lower odds for achieving pregnancy

Fact checked byRichard Smith
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Key takeaways:

  • Women had lower fecundability with increased exposure to certain types of phthalates.
  • No associations were observed between phthalate exposure and pregnancy loss.

Exposure to endocrine-disrupting phthalates may reduce women’s fecundability, or odds of becoming pregnancy during a menstrual cycle, according to findings published in Environmental Health Perspectives.

“Phthalates are endocrine-disrupting chemicals that may have harmful impacts on menstrual cycle function and how long it takes a woman to become pregnant,” Carrie Nobles, PhD, assistant professor of environmental health sciences in the School of Public Health and Health Sciences at University of Massachusetts Amherst, told Healio. “Among 1,228 women enrolled in a unique preconception study, we found higher preconception exposure to phthalates to be associated with elevated levels of inflammation and oxidative stress, changes in reproductive hormones across the menstrual cycle, and a longer time to pregnancy.”

Carrie Nobles, PhD

Researchers obtained data from 12,228 women who participated in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial from 2007 to 2011 (mean age, 28.7 years; 94.6% non-Hispanic white). In the trial, women aged 18 to 40 years with regular menstrual cycles between 21 and 42 days with no known diagnosis of infertility and one to two prior pregnancy losses were randomly assigned to 81 mg low-dose aspirin plus 400 µg folic acid or placebo plus folic acid at the beginning of the first observed menstrual cycle. Participants were followed for up to six menstrual cycles or throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured through urine samples collected at the beginning of the first menstrual cycle of follow-up. Fecundability was the number of cycles of follow-up a couple attempted to achieve pregnancy until a pregnancy occurred or the study ended. Pregnancy loss was the absence of pregnancy on clinical ultrasound at 6.5 weeks of gestation following a positive human chorionic gonadotropin test. Reproductive hormones and urinary creatinine were measured at four time points during each menstrual cycle.

Of the participants, 64.9% became pregnancy during the study, and 23.6% of women who became pregnant had a pregnancy loss.

Each interquartile range increase in exposure to mono-(2-ethylhexyl) phthalate (OR = 0.88; 95% CI, 0.78-1), mono-butyl phthalate (OR = 0.82; 95% CI, 0.7-0.96) and mono-benzyl phthalate (OR = 0.85; 95% CI, 0.74-0.98) reduced the odds for fecundability. Women with a BMI of at least 30 kg/m2 exposed to higher concentrations of the sum of di(2-ethylhexyl) phthalate metabolites also had lower fecundability odds (OR = 0.75; 95% CI, 0.58-0.97). No associations were observed between any phthalate metabolites and the likelihood for pregnancy loss.

“Prior research has suggested phthalates may increase risk of pregnancy loss, and it’s possible we may have missed the most relevant window for risk by looking at preconception vs. early pregnancy phthalate exposure,” Nobles said.

Six types of phthalate metabolites were associated with lower levels of estradiol across the menstrual cycle. Higher levels of most phthalates were associated with higher levels of follicle-stimulating hormone and luteinizing hormone. Associations between phthalates and progesterone were less consistent, but researchers found stronger associations between high phthalate concentrations and high progesterone during the luteal phase of the menstrual cycle.

In cross-sectional analyses, each interquartile range increase in exposure to phthalic acid (beta = 0.805 mg/dL; 95% CI, 0.185-1.426), mono-butyl phthalates (beta = 0.616 mg/dL; 95% CI, 0.068-1.165), mono-(3-carboxypropyl) phthalate (beta = 0.572 mg/dL; 95% CI, 0.06-1.084) and mono-(4-hydroxypentyl phthalate (beta = 0.537 mg/dL; 95% CI, 0.093-0.98) were associated with increased levels of high-sensitivity C-reactive protein.

“It was striking how strongly phthalates were associated with inflammation, oxidative stress and reproductive hormones,” Nobles said. “Although our study was focused on understanding effects of phthalate exposure among women trying to become pregnant, findings suggest phthalates may have broader impacts on menstrual cycle function and women’s reproductive health that remain understudied.”

For more information:

Carrie Nobles, PhD, can be reached at cnobles@umass.edu.