Abstract
STUDY QUESTION: Is exposure to toxic metal cadmium associated with increased endometriosis prevalence among a nationally representative sample of the US population? SUMMARY ANSWER: Concentrations of urinary cadmium, a long-term biomarker (10-30 years) of cadmium exposure, were associated with an increased prevalence of endometriosis. WHAT IS KNOWN ALREADY: Cadmium exhibits estrogenic properties and may increase the risk of endometriosis, a gynecologic condition associated with substantial morbidity, for which estrogen has a central pathogenic role. Previous epidemiological studies of cadmium and endometriosis have yielded mixed results, with null, positive, and inverse associations being reported. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from four cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2006. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population comprised participants aged 20-54 years who had an endometriosis diagnosis, available data on urinary cadmium, and a glomerular filtration rate ≥60 ml/min/1.73 m2 (unweighted n = 1647). Urinary cadmium was measured by inductively coupled plasma-mass spectrometry, and we used urinary creatinine concentrations and covariate-adjusted standardization to account for urinary dilution. Self-reported diagnosis of endometriosis was ascertained by interview. We examined the association between quartiles of urinary cadmium and endometriosis using log-binomial regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: We observed twice the prevalence of endometriosis for participants with cadmium concentrations in the second quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.9) and the third quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.7). Our data also suggested a 60% increased prevalence of endometriosis with urinary cadmium concentrations in the fourth quartile (versus the first quartile) (aPR 1.6, 95% CI: 0.8, 3.2). In a sensitivity analysis, restricting the study population to premenopausal participants with an intact uterus and at least one ovary (unweighted n = 1298), stronger associations accompanied by wider CIs were observed. LIMITATIONS, REASONS FOR CAUTION: We were limited by the ascertainment of urinary cadmium and endometriosis diagnosis at a single time point, given the cross-sectional study design, and we relied on self-report of endometriosis diagnosis. However, urinary cadmium characterizes long-term exposure and findings from validation studies suggest that misclassification of self-reported endometriosis diagnosis may be minimal. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that cadmium is associated with an increased endometriosis prevalence. Given the substantial morbidity conferred by endometriosis and that the general population is ubiquitously exposed to cadmium, further research is warranted to confirm our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institute of Nursing Research (grant R00NR017191 to K.U.) of the National Institutes of Health. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.