The role of exposure to phthalates in variations of anogenital distance: A systematic review and meta-analysis

Environmental chemicals such as phthalate esters may have adverse effects on anogenital distance (AGD), but the evidence in both genders has not been reviewed systematically. The objective of the present study is to conduct a systematic review and meta-analysis of studies that analyzed the relationship between exposure to phthalates and AGD. English papers published up to March 2018 were searched in PubMed, Scopus, Clarivate-Web of Science, and Google scholar. We applied fixed-effects models to calculate pooled beta coefficient [β]. In the case of heterogeneity, random-effects models were used. Using the comprehensive search strategies, 313 papers were identified and after screening, 10 of them were included in this study. In primary analyses, we found that exposure to phthalates was not associated with short AGD (β = −0.11; 95% CI, −0.27, 0.06; I² = 0%). However, results of subgroup analyses indicated that in boys, the sum of di-2-ethylhexyl phthalate (∑DEHP) metabolites had significant association with the risk of shortened anopenile distance (AGDAP) (β = −0.915, 95% CI: 1.629, −0.2) and anoscrotal distance (AGDAS) (β = −0.857, 95% CI: 1.455, −0.26). In addition, urinary monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monoisobutyl phthalate (MiBP) were associated with short AGDAP. We also observed significant association between monobenzylphthalate (MBzP) and anofourchette distance (AGDAF) in girls. Our study provided findings on significant association of exposure to ∑DEHP metabolites, MBP, MEP, and MiBP with shortened AGDAP in boys. The mechanisms of phthalates effect on AGD may involve receptors and enzymes involved in steroidgenesis, negative influence on Leydig cells, cell proliferation, gonocyte cell numbers, and testosterone production.