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. 2002 Jul;110(7):629–634. doi: 10.1289/ehp.02110629

Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Brenda Eskenazi 1, Paolo Mocarelli 1, Marcella Warner 1, Steven Samuels 1, Paolo Vercellini 1, David Olive 1, Larry L Needham 1, Donald G Patterson Jr 1, Paolo Brambilla 1, Nicoletta Gavoni 1, Stefania Casalini 1, Stefania Panazza 1, Wayman Turner 1, Pier Mario Gerthoux 1
PMCID: PMC1240907  PMID: 12117638

Abstract

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis.

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Selected References

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  1. Akins J. R., Waldrep K., Bernert J. T., Jr The estimation of total serum lipids by a completely enzymatic 'summation' method. Clin Chim Acta. 1989 Oct 16;184(3):219–226. doi: 10.1016/0009-8981(89)90054-5. [DOI] [PubMed] [Google Scholar]
  2. Bois F. Y., Eskenazi B. Possible risk of endometriosis for Seveso, Italy, residents: an assessment of exposure to dioxin. Environ Health Perspect. 1994 May;102(5):476–477. doi: 10.1289/ehp.94102476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carlsen E., Giwercman A., Keiding N., Skakkebaek N. E. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12;305(6854):609–613. doi: 10.1136/bmj.305.6854.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cummings A. M., Hedge J. M., Birnbaum L. S. Effect of prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice. Toxicol Sci. 1999 Nov;52(1):45–49. doi: 10.1093/toxsci/52.1.45. [DOI] [PubMed] [Google Scholar]
  5. Cummings A. M., Metcalf J. L., Birnbaum L. Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison. Toxicol Appl Pharmacol. 1996 May;138(1):131–139. doi: 10.1006/taap.1996.0106. [DOI] [PubMed] [Google Scholar]
  6. Eskenazi B., Warner M. L. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997 Jun;24(2):235–258. doi: 10.1016/s0889-8545(05)70302-8. [DOI] [PubMed] [Google Scholar]
  7. Eskenazi B., Warner M., Bonsignore L., Olive D., Samuels S., Vercellini P. Validation study of nonsurgical diagnosis of endometriosis. Fertil Steril. 2001 Nov;76(5):929–935. doi: 10.1016/s0015-0282(01)02736-4. [DOI] [PubMed] [Google Scholar]
  8. Gerhard I., Runnebaum B. Grenzen der Hormonsubstitution bei Schadstoffbelastung und Fertilitätsstörungen. Zentralbl Gynakol. 1992;114(12):593–602. [PubMed] [Google Scholar]
  9. Johnson K. L., Cummings A. M., Birnbaum L. S. Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls. Environ Health Perspect. 1997 Jul;105(7):750–755. doi: 10.1289/ehp.97105750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koninckx P. R., Braet P., Kennedy S. H., Barlow D. H. Dioxin pollution and endometriosis in Belgium. Hum Reprod. 1994 Jun;9(6):1001–1002. doi: 10.1093/oxfordjournals.humrep.a138623. [DOI] [PubMed] [Google Scholar]
  11. Kreuzer P. E., Csanády G. A., Baur C., Kessler W., Päpke O., Greim H., Filser J. G. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch Toxicol. 1997;71(6):383–400. doi: 10.1007/s002040050402. [DOI] [PubMed] [Google Scholar]
  12. Kurjak A., Kupesic S. Scoring system for prediction of ovarian endometriosis based on transvaginal color and pulsed Doppler sonography. Fertil Steril. 1994 Jul;62(1):81–88. doi: 10.1016/s0015-0282(16)56820-4. [DOI] [PubMed] [Google Scholar]
  13. Lebel G., Dodin S., Ayotte P., Marcoux S., Ferron L. A., Dewailly E. Organochlorine exposure and the risk of endometriosis. Fertil Steril. 1998 Feb;69(2):221–228. doi: 10.1016/s0015-0282(97)00479-2. [DOI] [PubMed] [Google Scholar]
  14. Mayani A., Barel S., Soback S., Almagor M. Dioxin concentrations in women with endometriosis. Hum Reprod. 1997 Feb;12(2):373–375. doi: 10.1093/humrep/12.2.373. [DOI] [PubMed] [Google Scholar]
  15. Mocarelli P., Brambilla P., Gerthoux P. M., Patterson D. G., Jr, Needham L. L. Change in sex ratio with exposure to dioxin. Lancet. 1996 Aug 10;348(9024):409–409. doi: 10.1016/s0140-6736(05)65030-1. [DOI] [PubMed] [Google Scholar]
  16. Needham L. L., Gerthoux P. M., Patterson D. G., Jr, Brambilla P., Turner W. E., Beretta C., Pirkle J. L., Colombo L., Sampson E. J., Tramacere P. L. Serum dioxin levels in Seveso, Italy, population in 1976. Teratog Carcinog Mutagen. 1997;17(4-5):225–240. [PubMed] [Google Scholar]
  17. Patterson D. G., Jr, Hampton L., Lapeza C. R., Jr, Belser W. T., Green V., Alexander L., Needham L. L. High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem. 1987 Aug 1;59(15):2000–2005. doi: 10.1021/ac00142a023. [DOI] [PubMed] [Google Scholar]
  18. Pauwels A., Schepens P. J., D'Hooghe T., Delbeke L., Dhont M., Brouwer A., Weyler J. The risk of endometriosis and exposure to dioxins and polychlorinated biphenyls: a case-control study of infertile women. Hum Reprod. 2001 Oct;16(10):2050–2055. doi: 10.1093/humrep/16.10.2050. [DOI] [PubMed] [Google Scholar]
  19. Peterson R. E., Theobald H. M., Kimmel G. L. Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. Crit Rev Toxicol. 1993;23(3):283–335. doi: 10.3109/10408449309105013. [DOI] [PubMed] [Google Scholar]
  20. Pirkle J. L., Wolfe W. H., Patterson D. G., Needham L. L., Michalek J. E., Miner J. C., Peterson M. R., Phillips D. L. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam Veterans of Operation Ranch Hand. J Toxicol Environ Health. 1989;27(2):165–171. doi: 10.1080/15287398909531288. [DOI] [PubMed] [Google Scholar]
  21. Rier S. E., Martin D. C., Bowman R. E., Dmowski W. P., Becker J. L. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundam Appl Toxicol. 1993 Nov;21(4):433–441. doi: 10.1006/faat.1993.1119. [DOI] [PubMed] [Google Scholar]
  22. Rier S. E., Turner W. E., Martin D. C., Morris R., Lucier G. W., Clark G. C. Serum levels of TCDD and dioxin-like chemicals in Rhesus monkeys chronically exposed to dioxin: correlation of increased serum PCB levels with endometriosis. Toxicol Sci. 2001 Jan;59(1):147–159. doi: 10.1093/toxsci/59.1.147. [DOI] [PubMed] [Google Scholar]
  23. Yang J. Z., Agarwal S. K., Foster W. G. Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the cynomolgus monkey. Toxicol Sci. 2000 Aug;56(2):374–381. doi: 10.1093/toxsci/56.2.374. [DOI] [PubMed] [Google Scholar]
  24. di Domenico A., Silano V., Viviano G., Zapponi G. Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. IV. Vertical distribution of TCDD in soil. Ecotoxicol Environ Saf. 1980 Sep;4(3):327–338. doi: 10.1016/0147-6513(80)90034-2. [DOI] [PubMed] [Google Scholar]

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