Menstrual cycle perturbation by organohalogens and elements in the Cree of James Bay, Canada

Abstract

Persistent organohalogens (POHs) and metals have been linked to alterations in menstrual cycle function and fertility in humans. The Cree First Nations people living near James Bay in Ontario and Quebec, Canada, have elevated levels of POHs, mercury and lead compared to other Canadians. The present study examines the interrelationships between selected POHs and elements on menstrual cycle function in these Cree women. Menstrual cycle characteristics were derived from structured daily diaries and endocrine measurements from daily urine samples collected during one cycle for 42 women age 19-42. We measured 31 POHs in blood plasma and 18 elements in whole blood, for 31 of the participants. POHs and elements detected in ≥ 70% of the participants were transformed by principal component (PC) analysis to reduce the contaminant exposure data to fewer, uncorrelated PCA variables. Multiple regression analysis revealed that, after adjusting for confounders, PC-3 values showed significant negative association with cycle length, after adjusting for confounders (p = 0.002). PC-3 accounted for 9.2% of the variance and shows positive loadings for cadmium, selenium, and PBDE congeners 47 and 153, and a negative loading for copper. Sensitivity analysis of the model to quantify likely effect sizes showed a range of menstrual cycle length from 25.3 to 28.3 days using the lower and upper 95% confidence limits of mean measured contaminant concentrations to predict cycle length. Our observations support the hypothesis that the menstrual cycle function of these women may be altered by exposure to POHs and elements from their environment.

Keywords: Cadmium; Cree; Hormones; Lead; Menstrual cycle; Mercury; Persistent organic pollutants.

Figure 1

a, b, c. Principal Components Analyses. Loadings for organohalogens and elements for the three largest principal components (PCs), which collectively account for 63.5% of the variance in the original matrix. The percentage of variation explained by each PC variable is presented in parenthesis in the axis label. Analytes included in the PCA were detectable in ≥70% of blood samples. See Table 4 for contaminant units. . All analytes were transformed by log10(x+1). . Figure 1a plots PC-1 loadings against PC-2 loadings. Figure 1b plots PC-1 against PC-3. Figure 1c plots PC-2 against PC-3.

Figure 1

a, b, c. Principal Components Analyses. Loadings for organohalogens and elements for the three largest principal components (PCs), which collectively account for 63.5% of the variance in the original matrix. The percentage of variation explained by each PC variable is presented in parenthesis in the axis label. Analytes included in the PCA were detectable in ≥70% of blood samples. See Table 4 for contaminant units. . All analytes were transformed by log10(x+1). . Figure 1a plots PC-1 loadings against PC-2 loadings. Figure 1b plots PC-1 against PC-3. Figure 1c plots PC-2 against PC-3.

Figure 1

a, b, c. Principal Components Analyses. Loadings for organohalogens and elements for the three largest principal components (PCs), which collectively account for 63.5% of the variance in the original matrix. The percentage of variation explained by each PC variable is presented in parenthesis in the axis label. Analytes included in the PCA were detectable in ≥70% of blood samples. See Table 4 for contaminant units. . All analytes were transformed by log10(x+1). . Figure 1a plots PC-1 loadings against PC-2 loadings. Figure 1b plots PC-1 against PC-3. Figure 1c plots PC-2 against PC-3.

Figure 2

a, b. Principle component (PC) scores for organohalogen and elements versus menstrual cycle length. Analytes included in the PCA were detectable in ≥70% of blood samples. See Table 4 for contaminant units. All analytes were transformed by log10(x+1). Figure 2a plots PC-3 loadings against menstrual cycle length. Figure 2b plots PC-1 loadings versus menstrual cycle length.

Figure 2

a, b. Principle component (PC) scores for organohalogen and elements versus menstrual cycle length. Analytes included in the PCA were detectable in ≥70% of blood samples. See Table 4 for contaminant units. All analytes were transformed by log10(x+1). Figure 2a plots PC-3 loadings against menstrual cycle length. Figure 2b plots PC-1 loadings versus menstrual cycle length.