A recent study published in the journal Environmental Health Perspectives evaluated the link between preconception phthalate exposure and fertility, pregnancy loss, and biomarkers for inflammation, hormone disruption, and oxidative stress.
Study: Preconceptional phthalate exposure and women’s reproductive health: pregnancy, pregnancy loss, and underlying mechanisms. Image credit: Dream Perfection / Shutterstock.com
What are Phthalates?
Phthalates are commonly used as stabilizers in personal care products and plasticizers in polyvinyl chloride. Sources of phthalate exposure include inhalation or ingestion from household products and food packaging, skin absorption from personal care products, and water pollution.
Phthalates act as endocrine disruptors and can systemically enhance oxidative stress and inflammation. Phthalate exposure is associated with adverse health outcomes such as chronic kidney disease, preterm birth, and poor neurodevelopment.
Due to the sensitivity of reproductive processes to oxidative stress and endocrine disruption, reproductive toxicity from phthalate exposure is particularly concerning. Moreover, various phthalates have been linked to antiandrogenic properties. Several studies suggest that phthalate exposure in males may impair testosterone and semen quality.
Phthalate exposure during pregnancy has also been linked to pregnancy loss and preterm birth. However, studies on the effects of phthalate exposure on achieving or maintaining a healthy pregnancy have yielded conflicting results.
About the Study
The researchers collected data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) study, where women attempting pregnancy between 2007 and 2011 were recruited.
Participants were randomized to receive 81mg of aspirin and 400 µg of folic acid or placebo and folic acid at the start of the first observed menstrual cycle. All participants were monitored for up to six menstrual cycles and, if pregnant, throughout the entire pregnancy.
Eligible individuals were aged 18–40, had regular menstrual cycles, had one or two prior pregnancy losses, had no history of infertility, had no contraindications to aspirin or indications for anticoagulant treatment, and were not being treated for a medical condition.
Participants self-reported data on age, ethnicity/race, parity, smoking, and medical history. Blood and morning urine samples were also collected.
Twenty phthalate metabolites were examined in urine samples. Pregnancy was determined through human chorionic gonadotropin (hCG) levels. Pregnancy loss was determined by the absence of ultrasound confirmation of pregnancy after a positive hCG or by observed loss after clinical confirmation.
Fertility was assessed by the number of menstrual cycles in which a couple attempted to conceive. Creatinine and reproductive hormones were measured in samples taken at different timepoints, including during the follicular, ovulatory, and luteal phases. At enrollment, high-sensitive C-reactive protein (hsCRP) in serum and isoprostanes in first morning urine samples were measured.
Cox proportional hazard models were used to assess the association between phthalate metabolites and fertility. Weighted Poisson models with robust variance were used to assess the risk of pregnancy loss. Generalized linear models were used to evaluate the associations of phthalate metabolites with changes in reproductive hormones, isoprostanes, and hsCRP.
A total of 1,228 women with an average age of about 29 participated in the EAGeR study. Approximately 95% of the participants were non-Hispanic white, 68.9% had a moderate to high income, 57.2% had parity, and 12.3% reported smoking.
Overall, 797 participants became pregnant, of whom 188 experienced pregnancy loss. Preconception values of several phthalate metabolites were associated with reduced likelihood of fertility.
There were no clear associations between phthalate metabolites and the risk of pregnancy loss. The effect estimates for pregnancy loss or fertility did not differ by randomization to aspirin or placebo. Additionally, preconceptional phthalate metabolites during the early two menstrual cycles of follow-up were associated with numerous reproductive hormones.
Elevated concentrations of several metabolites were consistently associated with reduced estradiol levels throughout the menstrual cycle. Furthermore, increased levels were consistently linked with higher levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), especially during ovulation. Associations with progesterone were less consistent.
Preconceptional concentrations of phthalate metabolites were associated with increased concentrations of isoprostanes and hsCRP. The three metabolites, Monobenzylphthalate, Monobutylphthalate, and Mono-(2-ethylhexyl)phthalate most strongly associated with fertility, were consistently linked to increased isoprostane and hsCRP concentrations.
Higher preconception values of phthalate metabolites were associated with reduced fertility and estradiol levels, as well as increased LH and FSH levels during ovulation. Additionally, there was no clear association between phthalate metabolites and the risk of pregnancy loss.
Various phthalate metabolites were linked to reduced fertility, changes in reproductive hormones, as well as increased oxidative stress and inflammation. The study findings suggest that preconceptional phthalate exposure may impair women’s reproductive health and that the pre- and periconceptional periods represent sensitive windows for interventions aimed at limiting the reproductive toxicity of phthalate exposure.
- Nobles, CJ, Mendola, P., Kim, K., et al. (2023). Preconceptional phthalate exposure and women’s reproductive health: pregnancy, pregnancy loss, and underlying mechanisms. Environmental Health Perspectives. doi:10.1289/EHP12287