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OD Research - Reproductive Epidemiology

Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study

Endometriosis is a gynecologic disorder affecting menstruating women and manifests as ectopic implantation of endometrial glands and stroma outside the uterine cavity. These endometrial implants may respond like normal endometrium to cyclic hormones and may manifest in pain and bleeding. While the etiology of endometriosis remains unknown, evidence is suggesting that endocrine-disrupting chemicals (EDCs) may be associated with the development of endometriosis. The ENDO Study was designed to address key methodologic challenges and to answer questions about the role of EDCs and newly diagnosed endometriosis. Specifically, we sought to assess whether 99 persistent and non-persistent EDCs were associated with endometriosis, and if the findings were consistent across samples and diagnostic methods. The ENDO Study utilized a matched exposure cohort design with surgery being the exposure. The operative sample comprised 495 women age 18 to 44 years undergoing laparoscopy or laparotomy at one of the 14 participating clinical sites in the Salt Lake City or San Francisco areas between 2007 and 2009. The population sample was designed to recruit women at risk for endometriosis (currently menstruating) and diagnosis (residence within clinical centers’ catchment areas) from the general population. The population cohort underwent pelvic magnetic resonance imaging (MRI) for the detection of endometriosis in light of having no indications for surgery. 

Following the baseline interview, all women completed standardized anthropometric assessments, the International Physical Activity Questionnaire and the 7-item BECK Depression Inventory Fast Screen before providing blood and urine samples for toxicologic analysis. Women were followed through surgery or MRI for the ascertainment of incident endometriosis.  The incidence of surgically visualized endometriosis for the operative sample was 41% and 11% for the population sample undergoing MRIs (Buck Louis et al., Fertil Steril 2011).

While most chemical classes of EDCs were associated with a higher odds of an endometriosis diagnosis, blood cadmium and specific congeners of polybrominated biphenyls ethers (PBDEs) and polychlorinated biphyenyls (PCBs) reflected a lower odds of disease. Only two chemical classes (hexachlorocyclohexane (HCH) and phthalates) reflected significantly elevated adjusted odds ratios (ORs) for women in the operative and population samples. In terms of non-persistent chemicals, mono-(2-ethylhexyl) phthalate (mEHP) also was consistently associated with a higher odds of endometriosis irrespective of sampling framework, meaning it was observed in both the operative and population groups (Buck Louis et al., Fertil Steril 2013). Two PFASs were associated with a higher odds of disease in the operative sample:  perfluorooctanoate (PFOA, AOR=1.89; 95% CI 1.17, 3.06) and perfluorononanonoate (PFNA, AOR=2.20; 95% CI 1.02, 4.75) (Buck Louis et al., Epidemiology, 2012).  We also found that one benzophenone UV-type filter (4OH-BP) was associated with endometriosis (AOR=1.19; 95% CI=1.01-1.41 Kunisue et al. 2012) in the population sample.

Principal Investigator

Germaine Louis, Ph.D., M.S.

DIPHR Collaborator

Zhen Chen, Ph.D.
Sunni Mumford, Ph.D., M.S.

Selected Publications

  • Buck Louis GM, Hediger ML, Peterson CM, Croughan M, Sundaram R, Stanford J, Chen Z, Fujimoto VY, Varner MW, Giudice LC; ENDO Study Working Group. Incidence of endometriosis by study population and diagnostic method: the ENDO study. Fertility and Sterility 2011; 96(2):360-365. PMID: 21719000. PMCID: PMC3143230
  • Buck Louis GM, Chen Z, Peterson CM, Hediger ML, Croughan MS, Sundaram R, Stanford JB, Varner MW, Fujimoto VY, Giudice LC, Trumble A, Parsons PJ, Kannan K. Persistent lipophilic environmental chemicals and endometriosis: The ENDO Study. Environmental Health Perspectives 2012; 120(6):811-816. PMID: 22417635. PMCID: PMC3385438
  • Kunisue T, Chen Z, Buck Louis GM, Sundaram R, Hediger ML, Sun L, Kannan K. Urinary concentrations of benzophenone-type UV filters in U.S. women and association with endometriosis. Environmental Science & Technology 2012; 46(8):4624-4632. PMID: 22417702. PMCID: PMC3352028
  • Schliep KC, Stanford JB, Chen Z, Zhang B, Chen Z, Dorais JK, Boiman Johnstone EB, Hammoud AO, Varner MW, Louis GM, Peterson CM. Interrater and intrarater reliability in the diagnosis and staging of endometriosis. Obstetrics and Gynecology 2012; 120(1):104-112. PMID: 22914398
  • Louis GM, Peterson MC, Chen Z, Hediger ML, Croughan MS, Sundaram R, Stanford JB, Fujimoto VY, Varner MW, Giudice LC, Kennedy A, Sun L, Wu Q, Kannan K. Perflurochemicals and Endometriosis: The ENDO Study. Epidemiology 2012; 23(6):799-805. PMID: 22992575. PMCID: PMC4122261
  • Thoma ME, Hediger ML, Sundaram R, Stanford JB, Peterson CM, Croughan MS, Chen Z, Buck Louis GM; ENDO Study Working Group. Comparing apples and pears:  women’s perceptions of their body size and shape. Journal of Women’s Health 2012; 21(10):1074-1081. PMID: 22873752. PMCID: PMC3466911
  • Wolff EF, Sun L, Hediger ML, Sundaram R, Peterson CM, Chen Z, Buck Louis GM. In utero exposures and endometriosis: the Endometriosis, Natural History, Disease, Outcome (ENDO) Study. Fertility and Sterility 2013; 99(3):790-795. PMID: 23211710. PMCID: PMC3604121
  • Peterson CM, Johnstone EB, Hammoud AO, Stanford JB, Varner MW, Kennedy A, Chen Z, Sun L, Fujimoto VY, Hediger ML, Buck Louis GM; ENDO Study Working Group. Risk factors associated with endometriosis: Importance of study population for characterizing disease in the ENDO Study. American Journal of Obstetrics and Gynecology 2013; 208(6):451.e1-11. PMID: 23454253. PMCID: PMC4114145
  • Steuerwald AJ, Parsons PJ, Arnason JG, Chen Z, Peterson CM, Louis GM. Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: Characterizing spectral interferences using inorganic mass spectrometry. Journal of Analytical Atomic Spectrometry 2013; 28(6):821-830. PMID: 27397951. PMCID: PMC4935091
  • Buck Louis GM, Peterson CM, Chen Z, Croughan M, Sundaram R, Stanford J, Varner MW, Kennedy A, Giudice L, Fujimoto VY, Sun L, Wang L, Guo Y, Kannan K. Bisphenol A and phthalates and endometriosis, The ENDO Study. Fertility and Sterility 2013; 100(1):162-169.e1-2. PMID: 23579005. PMCID: PMC3700684
  • Pollack AZ, Louis GM, Chen Z, Peterson CM, Sundaram R, Croughan MS, Sun L, Hediger ML, Stanford JB, Varner MW, Palmer CD, Steuerwald AJ, Parsons PJ. Trace element and endometriosis: the ENDO study. Reproductive Toxicology 2013; 42:41-48. PMID: 23892002. PMCID: PMC3836840
  • Williams KE, Miroshnychenko O, Johansen EB, Niles RK, Sundaram R, Kannan K, Albertolle M, Zhou Y, Prasad N, Drake PM, Giudice LC, Hall SC, Witkowska HE, Buck Louis GM, Fisher SJ. Urine, peritoneal fluid and omental fat proteomes of reproductive age women: endometriosis-related changes and associations with endocrine disrupting chemicals. Journal of Proteomics 2014; 113:194-205. PMID: 25284053. PMCID: PMC4467531
  • Johnstone EB, Louis GM, Parsons PJ, Steuerwald AJ, Palmer CD, Chen Z, Sun L, Hammoud AO, Dorais J, Peterson CM. Increased urinary cobalt and whole blood concentrations of cadmium and lead in women with uterine leiomyomata: Findings from the ENDO Study. Reproductive Toxicology 2014; 49:27-32. PMID: 24994689. PMCID: PMC4280339
  • Vitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck Louis GM, Hummelshoj L, Giudice LC, Stratton P, Adamson GD, Becker CM, Zondervan KT, Missmer SA; WERF EPHect Working Group. World Endometriosis Research Foundation endometriosis phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research. Fertility and Sterility 2014; 102(5):1223-1232. PMID: 25256930. PMCID: PMC4252538
  • Pollack AZ, Buck Louis GM, Chen Z, Sun L, Trabert B, Guo Y, Kannan K. Bisphenol A, benzophenone-type ultraviolet filters, and phthalates in relation to uterine leiomyoma. Environmental Research 2015; 137:101-107. PMID: 25531814. PMCID: PMC4355097
  • Schliep KC, Mumford SL, Peterson CM, Chen Z, Johnstone EB, Sharp HT, Stanford JB, Hammoud AO, Sun L, Buck Louis GM. Pain typology and incident endometriosis. Human Reproduction 2015; 30(10):2427-2438. PMID: 26269529. PMCID: PMC4573450
  • Trabert B, Chen Z, Kannan K, Peterson CM, Pollack AZ, Sun L, Buck Louis GM. Persistent organic pollutants (POPs) and fibroids: Results from the ENDO study. Journal of Exposure Science & Environmental Epidemiology 2015; 25(3):278-285. PMID: 24802554. PMCID: PMC4410838
  • Kim E, Zeng D, Zhou XH. Semi-parametric transformation models for multiple continuous biomarkers in ROC analysis. Biometrical Journal 2015; 57(5):808-833. PMID: 26138227 
  • Backonja U, Buck Louis GM, Lauver DR. Overall adiposity, adipose tissue distribution, and endometriosis: A systematic review.  Nursing Research 2016; 65(2):151-166. PMID: 26938364. PMCID: PMC4780367
  • Schliep KC, Mumford SL, Johnstone EB, Peterson CM, Sharp HT, Stanford JB, Chen Z, Backonja U, Wallace ME, Buck Louis GM. Sexual and Physical Abuse and Gynecologic Disorders. Human Reproduction 2016; 31(8):1904-1912. PMID: 27334336. PMCID: PMC4974667 [Available on 2017-08-01]
  • Buck Louis GM, Backjona U, Schliep KC, Sun L, Peterson CM, Chen Z. Women’s reproductive history before the diagnosis of incident endometriosis. Journal of Women’s Health 2016; 25(10):1021-1029. PMID: 27379997. PMID: PMC5111831 [Available on 2017-10-01]
  • Schliep K, Chen Z, Stanford JB, Xie Y, Hammoud AO, Johnstone E, Mumford SL, Dorais JK, Varner MW, Buck Louis GM, Peterson CM.  Endometriosis diagnosis and staging:  are surgeons’ diagnoses consistent?  British Journal of Obstetrics and Gynecology 2017; 124(4):220-229 . PMID: 26435386. PMCID: PMC4821828 [Available on 2018-01-01]
  • Backonja U, Hediger ML, Chen Z, Lauver DR, Sun L, Peterson CM, Buck Louis GM. Beyond body mass index: Using anthropometric measures and body composition indicators to assess odds of an endometriosis diagnosis. Journal of Women’s Health 2017 May 24. PMID: 28537460

Contact Information

Name: Constantine A. Stratakis, M.D., D(Med)Sc
Acting Director
Division of Intramural Population Health Research
Phone: 301-594-5984
E-mail: stratakc@mail.nih.gov

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