Table 1.
Study population, study design, outcome definition, and control/non-case selection for investigation of environmental contaminants and endometriosis risk
| First author, year (reference) | Location | Years | Study population | Inclusion/Exclusion criteria | Case definition | Control/non-case definition |
|---|---|---|---|---|---|---|
| ENDO Study | Operative cohort | |||||
| Buck Louis 2012 [35] Kunisue 2012 [36] Louis 2012 [37] Buck Louis 2013 [39] Pollack 2013 [40] | 5 hospital surgical centers in Salt Lake City, UT; 9 clinical centers in San Francisco, CA | 2007–2009 | Operative cohort: Patients scheduled for laparoscopy/laparotomy (n=473)a Indications: Pelvic pain (42%), pelvic mass (15%), menstrual irregularities (12%), fibroids (10%), tubal ligation (10%) and infertility (7%) [52] | Inclusion: Currently menstruating, ages 18–44, no breastfeeding for ≥6 months, no injectable hormone treatment within prior 2 years, no cancer history (other than nonmelanoma skin cancer); no history of surgically-confirmed endometriosis, communicate in English or Spanish | Incident, surgically-visualized endometriosis (n=190); rASRM staging conducted | No surgical visualization of endometriosis (n=283) |
| Population cohort | ||||||
| Geographic catchment areas within 50-mile radius of surgical/clinical centers in operative cohort | 2007–2009 | Population cohort: Selected from population registries matched to operative cohort on age and residence within 50-mile radius of clinical center; screened by pelvic MRI (n=127)a | Inclusion: Currently menstruating, ages 18–44, communicate in English or Spanish, no history of laparoscopy-confirmed endometriosis, willingness to undergo pelvic MRI | MRI-visualized endometriosis (primarily ovarian endometrioma) (n=14) [52] | No MRI-detected endometriosis (n=113) | |
| WREN Study | ||||||
| Trabert 2010 [31] Upson 2012 [41] Upson 2013 [42] Upson 2014 [44] | Integrated health care system, western Washington State, USA | 1996–2001 | Female health plan enrollees | Inclusion: Enrollees ages 18–49, premenopausal, intact uteri, at least one ovary, no prior diagnosis of endometriosis, enrollment in health plan for ≥6 months prior to reference dateb | Incident, surgically-visualized endometriosis, with definite or possible endometriotic disease (n=310) | Random sample of health plan enrollees without history of endometriosis diagnosis, frequency matched to cases on age (n=747) |
| Air (1) | ||||||
| Mahalingaiah 2014 [43] | All 50 United States and District of Columbia | 1989–2007 | Nurses’ Health Study II, female nurses ages 25–43 at enrollment in 1989; followed through May 2007; analyses included 84,060 women and 710,230 person-years of follow-up | Exclusion: Endometriosis diagnosis on or before 1993, no home address that could be geocoded | Self-report of incident physician-diagnosed, laparoscopy-confirmed endometriosis (n=2,486) | No self-report of physician-diagnosed, laparoscopy-confirmed endometriosis (n=81,574) |
| OCPs, PCBs, Dioxins, Furans, PBDEs, PBB (9) | ||||||
| Cooney 2010 [28] | Two university hospitals, Location not stated | 1999–2000 | Women ages 18–40 undergoing incident laparoscopy Indications: Not stated | Not stated | Laparoscopy-visualized endometriosis and serum lipid data (n=29); AFSr staging | No endometriosis visualized on laparoscopy, serum lipid data (n=51); Of all controls (n=52), 30 with gynecologic pathology; 22 without gynecologic pathology (ie. tubal sterilization) |
| Simsa 2010 [30] | University hospital/center Leuven, Belgium | 2001–2005 | Patients undergoing laparoscopy Indications: Infertility | Not stated | Laparoscopically and histologically proven endometriosis, with equal numbers for each AFSr stage (n=96) | Patients with laparoscopically “normal pelvis” with no evidence of endometriosis (n=106) |
| Trabert 2010 [31] | See WREN | Cases, n=251 | Controls, n=538 | |||
| Cai 2011 [33] | University OB/GYN department, Isehara, Kanagawa, Japan | 2004–2007 | Patients undergoing diagnostic laparoscopy Indications: Infertility | Not stated | Surgical visualization of endometriosis during laparoscopy, rASRM staging (n=10) | No surgical visualization of endometriosis during laparoscopy (n=7) |
| Buck Louis 2012 [35] | See ENDO | |||||
| Vichi 2012 [38] | University OB/GYN Department, Rome, Italy | 2002–2005 | Italian women ages 18–45 undergoing incidental laparoscopy Indications: Suspected endometriosis, other benign gynecologic conditions Additional control selection: No infertility or pelvic pain complaints, benign gynecologic conditions: 62% benign adnexal masses, 25% fallopian tube abnormalities/diseases, 14% uterine myomas | Inclusion: Age 18–45, residence in Rome past 5 years, nulliparity, no breastfeeding history, absence of immunologic, hormonal disorders, or chronic diseases, and no occupational exposure to PCBs or pesticides | Laparoscopy and histology confirmed endometriosis (n=181), rASRM staged, subset (n=63) with PCB data | No visual evidence of endometriosis with laparoscopy; No complaints of infertility, pelvic pain (n=162), subset (n=63) with PCB data |
| Upson 2013 [41] | See WREN | Cases, n=248 | Controls, n=538 | |||
| Martinez-Zamora 2015 [46] | University GYN department of tertiary referral hospital, Catalonia, Spain | Referred patients undergoing laparoscopy Indications: Cases: Suspected DIE Controls: Benign adnexal pathology; 80% ovarian cysts (functional, dermal, cystadenomas); 20% hydrosalpinx | Inclusion: Ages 18–40, BMI 18.5–25.0 kg/m2 Exclusion: History of cancer, suspected malignancy, previous abdominal surgery, autoimmune diseases, and any other chronic condition, previous pregnancies, previous breastfeeding, change of body weight >5 kg in last 5 years. | Patients underlying laparoscopic surgery due to suspected DIE (n=30) | Next consecutive patient undergoing laparoscopic surgery for benign adnexal gynecological diseases; no history of pelvic surgery; no suspicion of endometriosis during surgery or TVUS (n=30) | |
| Ploteau 2017 [49] | Study site not stated; Region Pays-de-Loire, France | 2013–2015 | Referred patients | Exclusion: History of cancer, suspected malignancy, autoimmune diseases, and any other chronic condition | Ages 18–45, surgical diagnosis of DIE, 26 with additional ovarian endometrioma, all cases AFSr stages III, IV (n=55) | No endometriosis during surgery for tubal ligation, genital prolapse surgery, ovarian cystectomy, without clinical symptoms, including CPP, dysmenorrhea, dyspareunia, history of infertility; matched to cases on age, race, BMI, breastfeeding history (n=44) [90] |
| Perfluoroalkyls (2) | ||||||
| Louis 2012 [37] | See ENDO | |||||
| Campbell 2016 [47] | United States | 2003–2006 | Nationally-representative sample NHANES 2003–2004 and 2005–2006 cycles (n=753, unweighted) | Inclusion: Women ages 20–50, self-report data on doctor-diagnosed endometriosis and serum PFAS measurements | Self-report of doctor-diagnosed endometriosis (n=54, unweighted) | No self-report of doctor-diagnosed endometriosis (n=699, unweighted) |
| Metals (2) | ||||||
| Pollack 2013 [40] | See ENDO | |||||
| Lai 2017 [48] | University hospital infertility clinic, Taipei, Taiwan | 2008–2010 | Patients undergoing laparoscopy Indications: First visit for infertility | Exclusion: Diagnoses of ovarian cyst, premature ovarian failure, repeated implantation failure or pregnancy; refused to provide blood sample; incomplete questionnaires | Laparoscopy and pathology-confirmed symptomatic endometriosis (chronic abdominal pain, diarrhea, dysmenorrhea, dyspareunia) or serum CA125 >35 U/ml, or ovarian endometrioma on transvaginal ultrasound (n=45)) or recurrent endometriosis and history of endometriomas and surgery (n=23); (n=68 total) | No evidence of endometriosis with laparoscopy or other examination, such as hystero-salpingography, semen analysis, and ultrasonagraphy, for tubal factor infertility, male factor infertility, or uterine myomas; no common symptoms (abdominal pain, diarrhea, dysmenorrhea, dyspareunia), serum CA125 levels >35 U/ml, nor ovarian endometrioma on TVUS) (n=122) |
| Bisphenol A, phthalate metabolites (9) | ||||||
| Huang 2010 [29] | OB/GYN diarrhea, dysmenorrhea, dyspareunia), serum CA125 levels >35 U/ml, nor ovarian endometrioma on TVUS) (n=122) | 2005–2007 | Patients undergoing laparotomy of Chinese descent Indications: Not stated | Exclusion: Those with pelvic masses on laparotomy, previous diagnosis of endometriosis, leiomyoma, or adenomyosis | Pathologic-confirmation of endometriosis (n=28) | Laparoscopy-confirmed absence of endometriosis, leiomyoma, and adenomyosis (n=29) |
| Weuve 2010 [32] | United States | 1999–2004 | Nationally-representative sample, NHANES 1999–2000, 2001–2002, 2003–2004 cycles | Inclusion: Women ages 20–54 years, urinary phthalate metabolite data, urinary creatinine 30–300 mg/dL, data on key covariates (n=1227); subset with two DEHP metabolite data (years 2001–2004), n=838 | Self-report of doctor-diagnosed endometriosis (n=87, unweighted) | No self-report of doctor-diagnosed endometriosis (n=1140, unweighted) |
| Kim 2011 [34] | Study site not stated; Korea | 2009 | Patients who underwent pelviscopic surgery, exploratory laparotomy, myomectomy, or transabdominal hysterectomy Indications: Provided for controls only | Exclusion: History of occupational exposure to reproductive toxicants, smoking, alcohol, or substance abuse, hormone therapy prior year, endometriosis stages I and II | Surgical and histologic evidence of endometriosis; all had sonographic evidence of ovarian endometrioma; stage III and IV endometriosis (ASRMr) (n=97) | No surgical or histologic evidence of endometriosis; no adenomyosis, invasive carcinoma of uterine cervix or ovarian cancer (n=169); reasons for surgery included ovarian cyst (32%, leiomyoma (59%), and uterine cervix carcinoma (9%) |
| Buck Louis 2013 [39] | See ENDO | |||||
| Upson 2013 [42] | See WREN | Cases, n=92 | Controls, n=195 | |||
| Upson 2014 [44] | See WREN | Cases, n=143 | Controls, n=287 | |||
| Kim 2015 [45] | OB/GYN Department, Seoul, Korea | 2012–2013 | Patients undergoing pelviscopic surgery, exploratory laparotomy, or transabdominal hysterectomy of Korean origin and from urban areas | Exclusion: History of occupational exposure to reproductive toxicants, smoking, alcohol, substance abuse, malignancy, hormone therapy prior year, minimal or mild-stage endometriosis; sonographic or laparoscopic evidence of leiomyoma or adenomyosis | Surgical and histologic evidence of stage III, IV endometriosis (ASRMr); all had ovarian endometrioma (n=55) | Patients without endometriosis (n=33); indications include ovarian cysts (91%) and carcinoma in situ of cervix (9%) |
| Rashidi 2017 [50] | Gynecology and infertility center, Tehran, Iran | 2013–2014 | Center patients Indications: Cases: Referred with ovarian endometrioma for operative laparoscopy and ovarian cystectomy Controls: Those previously seen at center for problem, returning for routine check-up | Exclusion: PCOS, uterine fibroma, diabetes mellitus, metabolic and endocrine disorders, cardiovascular disease history, BP >140/80, renal failure, BMI>30, neoplastic disorders, smoking | Sonographic evidence of endometrioma (n=50) | No sonographic evidence of endometrioma, no past or present symptoms related to endometrioma (n=50) |
| Moreira Fernandez 2019 [51] | Endometriosis center, university hospital Belo Horizonte, Brazil | Not stated | Brazilian women ages 18–45 undergoing videolaparoscopy surgery with visual inspection of pelvis and biopsy of suspected lesions Indications: Not stated | No inclusion or exclusion criteria provided | Cases (n=30): Histologic confirmation of endometriosis (n=27) or MRI (n=3) | No surgical visualization of endometriosis (n=22) |
| Benzophenone-type UV filters (1) | ||||||
| Kunisue 2012 [36] | See ENDO | |||||
Abbreviations: AFSr, American Fertility Society revised staging; BMI, body mass index; BP, blood pressure; BPA, Bisphenol A; CA, cancer antigen; CPP, chronic pelvic pain; DEHP, di(2-ethylhexyl) phthalate; DIE, deep infiltrating endometriosis; ENDO Study, Endometriosis: Natural History, Diagnosis and Outcomes Study; GYN, gynecology; MRI, magnetic resonance imaging; NHANES, National Health and Nutrition Examination Survey; OB, obstetrics; OCPs, organochlorine pesticides; PBB, polybrominated biphenyls; PBDEs, polybrominated diphenyl ethers; PCBs, polychlorinated biphenyls; PCOS, polycystic ovary syndrome; PFAS, perfluoroalkyl substances; rASRM, revised American Society for Reproductive Medicine classification; TVUS, transvaginal ultrasound; WREN, Women’s Risk of Endometriosis Study.
a
ENDO Study enrolled n=495 for the operative cohort, but 22 cancelled surgeries. ENDO Study also enrolled n=131 for the population cohort, but 4 were insufficient quality for diagnostic purposes [35].
b
Date of first visit in integrated health care system leading to endometriosis diagnosis in cases.