Lipophilic Environmental Chemicals and Endometriosis
The operative cohort comprised 495 women scheduled for surgery, and the population cohort comprised 131 women, representing 77% and 79% of eligible women in the target populations, respectively. Twenty-six women had no diagnostic information stemming from the cancellation of 22 (4%) surgeries or 4 (4%) unreadable MRIs in the operative and population cohorts, respectively, and were excluded from all analyses. Despite their different sampling frameworks, few differences were observed between cohorts (data not shown), with the exception of a higher percentage of married women in the operative than in the population cohort (76% vs. 60%, respectively), as previously reported (Buck Louis et al. 2011). The incidence of surgically visualized endometriosis was 41% in the operative cohort, whereas MRI-visualized endometriosis was 11% in the population cohort. Most of the cases in the operative cohort were not severe: 71% had stage 1 or 2, and 29% had stage 3 or 4. However, differences were observed by disease status. In the operative cohort, women with endometriosis were significantly younger, of lower parity, and leaner than women without endometriosis (Table 1). In the population cohort, women with endometriosis were comparable to women without disease, with one important difference—the absence of smokers among women with endometriosis (Table 1).
Table 2 presents the distributions of POPs by biological medium and disease status for each of the cohorts. Two differences emerged: a) the upper bound of all tertiles based on wet-weight concentrations was higher for the sum of OCPs (ΣOCPs), ΣPBDEs, and ΣPCBs when measured in fat than when measured in serum, and b) the geometric mean serum PBDE and PCB concentrations were slightly higher in women without versus women with endometriosis in the operative cohort, whereas the opposite pattern was observed for the population cohort. Significant mean differences in ΣPBDEs measured in fat were observed for the operative cohort, with higher concentrations for women without endometriosis than for women with endometriosis. The reverse pattern was observed for the population cohort for mean ΣPBDEs in serum. No other patterns were evident for the remaining POPs by endometriosis status. The distributions for all individual chemicals by biological medium, cohort, and endometriosis status are provided in Supplemental Material, Table 1 and Table 2 (http://dx.doi.org/10.1289/ehp.1104432). Lipid adjusted fat and serum concentrations also are provided in Supplemental Material, Table 3.
Table 3 presents the logistic regression results for each chemical observed to be significantly associated with the odds of an endometriosis diagnosis in each cohort and by biological medium. Results for all chemicals not achieving significance are provided in Supplemental Material, Table 4 (http://dx.doi.org/10.1289/ehp.1104432). Several noteworthy patterns emerged, including the absence of consistent chemical effects across biological media or cohorts and a modest attenuation in the magnitude of point estimates after adjustment, although with no change in the direction of the adjusted ORs (AORs). In the operative cohort, where chemicals could be measured in fat, γ-HCH was positively associated with endometriosis (per 1-SD increase: AOR = 1.27; 95% CI: 1.01, 1.59). Of note are the three compounds associated with reduced odds of diagnosis: PBDE-47 (AOR = 0.70; 95% CI: 0.55, 0.90), PCB-74 (AOR = 0.72; 95% CI: 0.55, 0.93), and PCB-156 (AOR = 0.74; 95% CI: 0.57, 0.96). Serum β-HCH was the only POP that showed a statistically signficant association with endometriosis in the population cohort (per 1-SD increase: AOR = 1.72; 95% CI: 1.09, 2.72).
We conducted a number of sensitivity analyses to assess the robustness of our primary findings, given different modeling assumptions (data not shown). Given the uncertain role of breast-feeding and parity in the etiologic pathway, we removed it from the model and observed similar associations for fat γ-HCH (AOR = 1.26; 95% CI: 1.00, 1.58) and serum β-HCH (AOR = 1.70; 95% CI: 1.08, 2.66) in the operative and population cohorts, respectively. A reversal in the direction of the AOR was observed for fat γ-HCH when restricting the endometriosis to include visualization and histology (AOR = 0.86; 95% CI: 0.57, 1.28) and to stages 2 and 4 (AOR = 0.86; 95% CI: 0.47, 1.55). The AOR remained elevated for fat γ-HCH (AOR = 1.31; 95% CI: 0.96, 1.79) when restricting the comparison women to those with a postoperative diagnosis of a normal pelvis. We also noted an association with two other POPs in this analysis using fat concentrations: a) PBDE-183 (AOR = 1.55; 95% CI: 1.06, 2.26) and b) PCB-151 (AOR = 3.23; 95% CI: 1.43, 7.28).
Results
The operative cohort comprised 495 women scheduled for surgery, and the population cohort comprised 131 women, representing 77% and 79% of eligible women in the target populations, respectively. Twenty-six women had no diagnostic information stemming from the cancellation of 22 (4%) surgeries or 4 (4%) unreadable MRIs in the operative and population cohorts, respectively, and were excluded from all analyses. Despite their different sampling frameworks, few differences were observed between cohorts (data not shown), with the exception of a higher percentage of married women in the operative than in the population cohort (76% vs. 60%, respectively), as previously reported (Buck Louis et al. 2011). The incidence of surgically visualized endometriosis was 41% in the operative cohort, whereas MRI-visualized endometriosis was 11% in the population cohort. Most of the cases in the operative cohort were not severe: 71% had stage 1 or 2, and 29% had stage 3 or 4. However, differences were observed by disease status. In the operative cohort, women with endometriosis were significantly younger, of lower parity, and leaner than women without endometriosis (Table 1). In the population cohort, women with endometriosis were comparable to women without disease, with one important difference—the absence of smokers among women with endometriosis (Table 1).
Table 2 presents the distributions of POPs by biological medium and disease status for each of the cohorts. Two differences emerged: a) the upper bound of all tertiles based on wet-weight concentrations was higher for the sum of OCPs (ΣOCPs), ΣPBDEs, and ΣPCBs when measured in fat than when measured in serum, and b) the geometric mean serum PBDE and PCB concentrations were slightly higher in women without versus women with endometriosis in the operative cohort, whereas the opposite pattern was observed for the population cohort. Significant mean differences in ΣPBDEs measured in fat were observed for the operative cohort, with higher concentrations for women without endometriosis than for women with endometriosis. The reverse pattern was observed for the population cohort for mean ΣPBDEs in serum. No other patterns were evident for the remaining POPs by endometriosis status. The distributions for all individual chemicals by biological medium, cohort, and endometriosis status are provided in Supplemental Material, Table 1 and Table 2 (http://dx.doi.org/10.1289/ehp.1104432). Lipid adjusted fat and serum concentrations also are provided in Supplemental Material, Table 3.
Table 3 presents the logistic regression results for each chemical observed to be significantly associated with the odds of an endometriosis diagnosis in each cohort and by biological medium. Results for all chemicals not achieving significance are provided in Supplemental Material, Table 4 (http://dx.doi.org/10.1289/ehp.1104432). Several noteworthy patterns emerged, including the absence of consistent chemical effects across biological media or cohorts and a modest attenuation in the magnitude of point estimates after adjustment, although with no change in the direction of the adjusted ORs (AORs). In the operative cohort, where chemicals could be measured in fat, γ-HCH was positively associated with endometriosis (per 1-SD increase: AOR = 1.27; 95% CI: 1.01, 1.59). Of note are the three compounds associated with reduced odds of diagnosis: PBDE-47 (AOR = 0.70; 95% CI: 0.55, 0.90), PCB-74 (AOR = 0.72; 95% CI: 0.55, 0.93), and PCB-156 (AOR = 0.74; 95% CI: 0.57, 0.96). Serum β-HCH was the only POP that showed a statistically signficant association with endometriosis in the population cohort (per 1-SD increase: AOR = 1.72; 95% CI: 1.09, 2.72).
We conducted a number of sensitivity analyses to assess the robustness of our primary findings, given different modeling assumptions (data not shown). Given the uncertain role of breast-feeding and parity in the etiologic pathway, we removed it from the model and observed similar associations for fat γ-HCH (AOR = 1.26; 95% CI: 1.00, 1.58) and serum β-HCH (AOR = 1.70; 95% CI: 1.08, 2.66) in the operative and population cohorts, respectively. A reversal in the direction of the AOR was observed for fat γ-HCH when restricting the endometriosis to include visualization and histology (AOR = 0.86; 95% CI: 0.57, 1.28) and to stages 2 and 4 (AOR = 0.86; 95% CI: 0.47, 1.55). The AOR remained elevated for fat γ-HCH (AOR = 1.31; 95% CI: 0.96, 1.79) when restricting the comparison women to those with a postoperative diagnosis of a normal pelvis. We also noted an association with two other POPs in this analysis using fat concentrations: a) PBDE-183 (AOR = 1.55; 95% CI: 1.06, 2.26) and b) PCB-151 (AOR = 3.23; 95% CI: 1.43, 7.28).
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