Does prenatal exposure to phthalates lead to decreased penile length and width in the offspring? The testicular dysgenesis syndrome hypothesis revisited
Rodrigo LP Romao, MD1, Linda Dodds, PhD1, Jillian Ashley-Martin, PhD1, Patricia Monnier, MD, PhD2, Tye Arbuckle, PhD3.
1IWK Health Centre, Dalhousie University, Halifax, NS, Canada, 2Research Institute McGill University Health Centre (MUHC), MUHC Reproductive Centre, Montreal, QC, Canada, 3Health Canada, Ottawa, ON, Canada.
Introduction: The testicular dysgenesis syndrome hypothesis suggests that exposure to endocrine disrupting chemicals (EDCs) with anti-androgenic effects have a negative impact on male reproductive development, potentially leading to an increased risk of developing hypospadias, testicular cancer and infertility. Phthalates are a group of EDCs ubiquitously present in the environment. The objective of this study was to determine if prenatal exposure to phthalates was associated with reduced penile length/width at birth in full term singleton boys.
Materials & Methods: In the MIREC (Maternal-Infant Research on Environmental Chemicals) prospective cohort study, 2001 pregnant women from 10 Canadian cities were recruited and provided biospecimens for measurement of chemicals, including phthalates. Urinary concentrations of 11 phthalate metabolites were measured in the first trimester of pregnancy. Total high and low molecular weight phthalates and the sum of Di-2-ethylhexyl phthalate (DEHP) metabolite concentrations were calculated based on the molar sum of their respective metabolites. At birth, multiple anthropometric measurements including penile length (PL) and width (PW) were conducted for 215 male newborns. Trained personnel performed 3 consecutive measurements of PL and PW. Maternal (age, parity, smoking status, household income, education, race, BMI, comorbidities), infant (gestational age at birth, birthweight/length, weight-for-length z-score) and urinary covariates (specific gravity, time of day/season of collection, time since last void) were collected. Univariate and multivariate linear regressions were performed to study the association between penile measurements and maternal urinary concentrations of each phthalate metabolite and composite measures adjusting for potential confounders. Exposure levels did not follow a normal distribution and were log-transformed for the analysis. A p<0.05 was considered statistically significant.
Results: 170 term male newborns had complete exposure and outcome data for analysis; 4 phthalate metabolites with high (>50%) undetectable levels were excluded. Average PL and PW
were 21.47±4.28 and 10.45±2.02 mm, respectively. Both measurements displayed good intra-rater reliability and similar variance across centers. On univariate analysis, no association was found between the individual levels of 7 phthalate metabolites, DEHP, low or high molecular weight phthalates and PL/PW. Comparably, on multivariate analysis controlling for infant's size, gestational age, urinary specific gravity, center of enrollment and other potential confounders, no association was found between PL / PW and the levels of any of the phthalate metabolites (table).
Conclusions: Our study of the association between maternal urinary levels of phthalate metabolites in the 1st trimester of pregnancy and penile measurements (length and width) yielded no significant findings for individual phthalate metabolite levels, or the sums of DEHP, low or high molecular weight phthalates in univariate and multivariate analyses. The main limitation is that exposure to phthalates was assessed based on a single measurement in the first trimester of pregnancy. Future studies with serial phthalates measurements are warranted to confirm these findings.
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