Biomarkers of phthalates and inflammation: Findings from a subgroup of Women's Health Initiative participants

Background: Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders. Objectives: We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI). Methods: A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI. Results: In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (beta = 0.092; 95% CI 0.026, 0.158) and IL-6 (beta = 0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (beta = -0.019; 95% CI -0.036, -0.001) and monobenzyl phthalate (MBzP) (beta = -0.034; 95% CI -0.058, -0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels. Conclusions: Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI.

Automated summary

The study aimed to investigate the relationship between phthalate exposure and inflammatory markers CRP and IL-6 in postmenopausal women. Positive associations were found between some phthalates (e.g. MCNP) and CRP/IL-6, but these associations were attenuated after adjustment for BMI. Inverse associations with CRP were observed for other phthalates (e.g. MEP and MBzP) only after adjusting for BMI.