Objective
We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study.
Study Design
In this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort.
Results
The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57−3.76) and population (AOR, 7.91; 95% CI, 1.69−37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28−4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44−5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32−0.75), parity (AOR, 0.42; 95% CI, 0.28−0.64), and body mass index (AOR, 0.95; 95% CI, 0.93−0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor.
Conclusion
An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.
Endometriosis has been clinically recognized since 1860. The prevalence of endometriosis in women varies widely: 0.7-11% in populations presenting for health care, 2-22% when undergoing surgical sterilization, 17-47% among infertile women, and 2-74% in women with chronic pelvic pain. Recently, we reported that the incidence of endometriosis varied by a magnitude of 2 depending upon the study population and diagnostic criteria employed in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. The variability in the reported prevalence and incidence of endometriosis raises questions regarding the consistency of risk factors for an endometriosis diagnosis or for informing about its etiology. Reports to date have largely relied upon a single study cohort/sample, which precludes assessment of the consistency/validity of so-called risk factors across different cohorts.
Prior studies identified a variety of endometriosis risk factors including abnormal or heavy bleeding, cyclic gastrointestinal/urinary symptoms, dyschezia, dysmenorrhea, dyspareunia, dysuria, and pelvic pain. Increasing age, alcohol use, early menarche, family history of endometriosis, infertility, intercourse during menses, low body weight, prolonged menstrual flow, and short cycle interval are also alleged risk factors. Endometriosis has been negatively associated with exercise and smoking. Recently, red hair, blue or green eyes, and freckles have been reported to increase the odds of diagnosis. The plethora of risk factors for endometriosis may reflect varying methodologies such as study populations, definitions utilized for risk factors, and diagnostic accuracy. Our aim is to assess previously reported risk factors for endometriosis and their consistency across study cohorts in the ENDO Study to identify variations in risk factors, and how they may inform regarding etiology.
Materials and Methods
Study design and populations
The ENDO Study was specifically designed and implemented to identify environmental (nongenetic) determinants for endometriosis including persistent environmental chemicals and lifestyle in the context of somatic signs and symptoms. A prospective matched (with surgery being the exposure) cohort design was utilized to assess the robustness of findings across study populations and diagnostic methods. The operative cohort comprised 495 currently menstruating women, aged 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of 5 participating surgical facilities located in the Salt Lake City area (n = 432) or 1 of 9 sites in the San Francisco area (n = 63) in 2007 through 2009. Exclusion criteria included: previous laparoscopic diagnosis of endometriosis; currently breast-feeding ≥6 months (because of its likely impact lowering concentrations of environmental chemicals); history of cancer other than nonmelanoma skin cancer; use of injectable hormonal therapy within the past 2 years that may affect somatic presentation; and inability to communicate in Spanish or English. Any surgical indication was acceptable and included pelvic pain (n = 206, 42%), pelvic mass (n = 74, 15%), menstrual irregularities (n = 60, 12%), fibroids (n = 49, 10%), tubal ligation (n = 48, 10%), and infertility (n = 35, 7%). The population cohort was matched to the surgical cohort on both age and residence within a 50-mile geographic catchment area for the participating clinical centers, and included 131 currently menstruating women without a history of surgically confirmed endometriosis. Sampling frameworks for defining the population cohorts included the Utah Population Database and the InfoUSA California directory to ensure both cohorts arose from the same geographic referent population. The population cohort was defined to be at risk for endometriosis (currently menstruating) and opportunity for diagnosis (residence in the clinical catchment area) in an attempt to overcome key methodologic challenges underlying endometriosis research that requires adherence to the gold standard of visualized disease. More complete details regarding the design and methodology of the ENDO Study are provided elsewhere.
Data collection
All women were given a study packet introducing the study prior to enrollment. Research assistants subsequently screened and recruited women by telephone or in person. Briefly, the standardized data collection protocol included a computer-assisted interview administered at baseline, an anthropometric assessment including body mass index (BMI) and skin-fold measurements, and biospecimen collection for quantification of environmental chemicals. Women were queried regarding sociodemographic characteristics, medical and reproductive history, pain, and lifestyle. The protocol was administered prior to surgery for the operative cohort and at the earliest convenience for the population cohort (approximately 2 months before surgery or magnetic resonance imaging [MRI]). Completion rates were 95% and 98% for the operative and population cohorts, respectively.
Surgeons completed a standardized operative report immediately following surgery to capture gynecologic pathology and endometriosis diagnosis and staging using the revised criteria from the American Society for Reproductive Medicine (rASRM). A computerized algorithm was also developed for the automatic calculation of severity and categorized as stage 1 (minimal) to 4 (severe) disease.
Magnetic resonance imaging
All women in the population cohort (without prior surgery) underwent a pelvic MRI to assess visceral fat distribution and any gynecologic pathology including endometriosis. Using Food and Drug Administration–approved protocol for pelvic imaging, 1 radiologist supervised and evaluated all MRI. All findings were confirmed by a second radiologist with special expertise in gynecologic imaging.
Human subjects and monitoring
Remuneration was provided for time and travel. Full human subjects’ approval was awarded by all participating research institutions; all women provided written informed consent prior to any data collection.
Operational definitions
Endometriosis diagnoses were derived from visualization by the surgeon in the operative cohort and from MRI in the population cohort. Histologically confirmed endometriosis required the presence of endometrial glands and/or stroma and/or hemosiderin-laden macrophages. MRI-visualized endometriosis comprised primarily ovarian endometriomas, but also included nodular implants. rASRM staging was categorized as: stage I, minimal (scores 1-5); stage II, mild (scores 6-15); stage III, moderate (scores 16-40); or stage IV, severe (scores >40).
Statistical analysis
The analysis was conducted in 2 phases with separate analyses for each cohort. First, descriptive analyses were undertaken to inspect the completeness and consistency of data, and to identify risk factors associated with endometriosis diagnosis for both cohorts. Potential risk factors were identified a priori based on prior literature and these were included in the ENDO instruments. Significance was estimated using either the χ 2 statistic or the Student t test for categorical and continuous variables, respectively. In the analytic phase, unadjusted odds ratios (ORs) and accompanying 95% confidence intervals (CIs) were estimated for all risk factors observed to be significant in the descriptive phase of research using logistic regression. We conservatively estimated ORs rather than relative risks, given our uncertainty about the timing of onset for incident endometriosis. Subsequently, a logistic regression model was specified to include all significant ORs along with age (in years) and clinical site (Utah or California) to account for potential residual confounding. Separate models were run for each cohort. To assess the robustness of findings, several sensitivity analyses were undertaken by restricting endometriosis to be visually and histologically confirmed disease, restricting to moderate or severe disease (stages 3 and 4), or restricting the comparison group of women to those with a postoperative diagnosis of a “normal pelvis.” Twenty-two (4%) women in the operative cohort had no diagnostic information, given cancellations of their surgeries. Also, 4 (3%) women in the population cohort had unreadable MRIs. The absence of diagnostic information for these 26 women necessitated their removal from analyses. All statistical analyses were conducted using SAS, version 9.1 (SAS Institute, Cary, NC).
Results
The incidence of surgically visualized endometriosis in the operative cohort was 40% (190/473 with 11.8% [56/473] moderate/severe and 28.3% [134/473] minimal/mild) and 11% (14/127) in the population cohort based on MRI. MRI-visualized endometriosis in the population cohort consisted of primarily ovarian endometriomas, and included nodular implants (stage 3-4 by rASRM).
Only a few significant differences in reproductive history were observed by endometriosis status, with some difference by cohort ( Table 1 ). Women with endometriosis had lower mean gravidity (1.7 ± 2.0) than unaffected women (2.3 ± 2.1), and lower parity (ie, 1.8 ± 1.3 and 2.2 ± 1.4, respectively) in the operative cohort. While not significant, a reverse pattern for gravidity and parity was observed in the population cohort. A higher percentage of women with endometriosis reported prior infertility treatment than women without endometriosis in both the operative (34% and 17%, respectively) and population (29% and 5%, respectively) cohorts ( Table 1 ). With regard to menstruation history, women in the operative cohort with endometriosis reported more pelvic pain or dysmenorrhea in the past year than women without endometriosis ( Table 2 ).
| Characteristic | Operative cohort n = 473 | Population cohort n = 127 | ||
|---|---|---|---|---|
| Endometriosis n = 190 n (%) | No endometriosis n = 283 n (%) | Endometriosis n = 14 n (%) | No endometriosis n = 113 n (%) | |
| Age, y | ||||
| <20 | 5 (2.6) | 7 (2.5) | 0 (0) | 4 (3.5) |
| 20-24 | 22 (11.6) | 26 (9.2) | 4 (28.6) | 21 (18.6) |
| 25-29 | 48 (25.3) | 55 (19.5) | 1 (7.1) | 22 (19.5) |
| 30-34 | 44 (23.2) | 58 (20.6) | 2 (14.3) | 18 (15.9) |
| ≥35 | 71 (37.4) | 136 (48.2) | 7 (50) | 48 (42.5) |
| Mean (SD) | 31.98 (6.75) | 33.61 (7.09) a | 33.14 (8.33) | 32.07 (7.76) |
| Ever sexually active | ||||
| No | 27 (14.2) | 37 (13.2) | 1 (7.1) | 14 (12.4) |
| Yes | 163 (85.8) | 244 (86.8) | 13 (92.9) | 99 (87.6) |
| Age at first consenting sex | ||||
| ≤17 | 92 (48.4) | 157 (55.5) | 4 (28.6) | 55 (48.7) |
| 18-20 | 50 (26.3) | 67 (23.7) | 6 (42.9) | 38 (33.6) |
| ≥21 | 48 (25.3) | 59 (20.8) | 4 (28.6) | 20 (17.7) |
| Mean (±SD) | 19.19 (4.28) | 18.33 (3.83) | 19.08 (2.47) | 18.49 (2.99) |
| Ever use oral contraceptives | ||||
| No | 21 (11.1) | 45 (15.9) | 1 (7.1) | 17 (15) |
| Yes | 169 (88.9) | 238 (84.1) | 13 (92.9) | 96 (85) |
| Gravidity | ||||
| Nulligravid (0) | 81 (42.6) | 74 (26.3) b | 5 (35.7) | 46 (40.7) |
| Gravid (≥1) | 109 (57.4) | 207 (73.7) | 9 (64.3) | 67 (59.3) |
| Mean (±SD) | 1.65 (1.98) | 2.28 (2.12) c | 2.21 (2.08) | 1.65 (1.80) |
| Parity (no. of live births) | ||||
| Nulliparous | 21 (19.4) | 25 (12.1) | 1 (11.1) | 10 (14.9) |
| Parous | 87 (80.6) | 182 (87.9) | 8 (88.9) | 57 (85.1) |
| Mean (±SD) | 1.81 (1.27) | 2.19 (1.44) d | 2.56 (1.59) | 2.21 (1.45) |
| Age at first pregnancy, y | ||||
| <20 | 42 (38.5) | 79 (38.2) | 0 (0) | 14 (20.9) |
| 20-24 | 42 (38.5) | 71 (34.3) | 5 (55.6) | 27 (40.3) |
| 25-29 | 20 (18.3) | 33 (15.9) | 4 (44.4) | 20 (29.9) |
| 30-34 | 4 (3.7) | 22 (10.6) | 0 (0) | 4 (6) |
| 35-39 | 1 (0.9) | 1 (0.5) | 0 (0) | 1 (1.5) |
| ≥40 | 0 (0) | 1 (0.5) | 0 (0) | 1 (1.5) |
| Mean (±SD) | 21.63 (4.19) | 21.98 (5.13) | 23.56 (2.79) | 23.64 (4.99) |
| History STIs | ||||
| No | 160 (84.2) | 219 (77.4) | 13 (92.9) | 91 (80.5) |
| Yes | 30 (15.8) | 64 (22.6) | 1 (7.1) | 22 (19.5) |
| History of abnormal pap smear | ||||
| No | 148 (77.9) | 210 (74.2) | 12 (85.7) | 80 (70.8) |
| Yes | 42 (22.1) | 73 (25.8) | 2 (14.3) | 33 (29.2) |
| Ever seek infertility treatment | ||||
| No | 126 (66.3) | 235 (83.0) e | 10 (71.4) | 107 (94.7) f |
| Yes | 64 (33.7) | 48 (17.0) | 4 (28.6) | 6 (5.3) |
| Surgical indication | ||||
| Pelvic pain | 120 (63.2) | 86 (30.5) g | ||
| Pelvic mass | 26 (13.7) | 48 (17.0) | ||
| Menstrual irregularity | 20 (10.5) | 40 (14.2) | ||
| Fibroids | 9 (4.7) | 40 (14.2) | ||
| Tubal ligation | 8 (4.2) | 40 (14.2) | ||
| Infertility | 7 (3.7) | 28 (9.9) | ||
| Characteristic | Operative cohort n = 473 | Population cohort n = 127 | ||
|---|---|---|---|---|
| Endometriosis n = 190 n (%) | No endometriosis n = 283 n (%) | Endometriosis n = 14 n (%) | No endometriosis n = 113 n (%) | |
| Menarche, y | ||||
| ≤11 | 37 (19.9) | 48 (17.3) | 2 (15.4) | 18 (16.5) |
| 12-13 | 87 (46.8) | 146 (52.5) | 5 (38.5) | 61 (56.0) |
| ≥14 | 62 (33.3) | 84 (30.2) | 6 (46.2) | 30 (27.5) |
| Mean (±SD) | 13.0 (1.8) | 12.8 (1.6) | 13.2 (1.5) | 12.7 (1.5) |
| No. of menstrual cycles in past 12 mo | ||||
| None | 5 (2.6) | 13 (4.6) a | 1 (7.1) | 4 (3.6) |
| 1-3 | 5 (2.6) | 20 (7.1) | 0 (0.0) | 4 (3.6) |
| 4-6 | 8 (4.2) | 23 (8.2) | 2 (14.3) | 11 (9.8) |
| 7-9 | 20 (10.6) | 17 (6.0) | 0 (0.0) | 10 (8.9) |
| 10-12 | 128 (67.7) | 158 (56.2) | 11 (78.6) | 72 (64.3) |
| ≥13 | 23 (12.2) | 50 (17.8) | 0 (0.0) | 11 (9.8) |
| Mean (±SD) | 11.0 (3.5) | 11.3 (8.5) | 10.1 (4.0) | 11.2 (11.1) |
| Average cycle length in past 12 mo b | ||||
| <22 | 24 (13.2) | 54 (20.3) | 1 (8.3) | 5 (4.7) |
| 22-24 | 5 (2.7) | 10 (3.8) | 0 (0.0) | 7 (6.6) |
| 25-27 | 22 (12.1) | 27 (10.1) | 3 (25.0) | 24 (22.6) |
| 28-30 | 105 (57.7) | 139 (52.3) | 7 (58.3) | 54 (50.9) |
| 31-33 | 12 (6.6) | 9 (3.4) | 0 (0.0) | 4 (3.8) |
| ≥34 | 14 (7.7) | 27 (10.2) | 1 (8.3) | 12 (11.3) |
| Mean (±SD) | 28.1 (8.7) | 31.6 (31.7) | 27.4 (3.5) | 30.3 (11.1) |
| Mean (±SD) length of shortest cycle in past 12 mo, d b | 18.2 (10.6) | 21.3 (29.6) | 30.5 (18.2) | 26.8 (10.9) |
| Mean (±SD) length of longest cycle in past 12 mo, d b | 28.8 (22.7) | 34.2 (39.4) c | 37.7 (34.1) | 33.6 (15.2) |
| Few periods than normal in past 12 mo? | ||||
| No | 161 (85.2) | 236 (84.0) | 13 (92.9) | 88 (78.6) |
| Yes, no medications | 1 (0.5) | 4 (1.4) | 0 (0.0) | 1 (0.9) |
| Yes, medications | 27 (14.3) | 41 (14.6) | 1 (7.1) | 23 (20.5) |
| Periods in past 12 mo typical of last 5 y | ||||
| Yes | 83 (43.9) | 95 (33.9) | 4 (28.6) | 58 (52.3) |
| No; specify | 106 (56.1) | 185 (66.1) | 10 (71.4) | 53 (47.7) |
| More frequent | 29 (27.4) | 54 (29.2) | 1 (10.0) | 12 (22.6) |
| Less frequent | 17 (16.0) | 32 (17.3) | 3 (30.0) | 14 (26.4) |
| Heavier bleeding | 72 (67.9) | 102 (55.1) | 1 (10.0) | 22 (41.5) |
| Lighter bleeding | 24 (22.6) | 53 (28.6) | 7 (70.0) | 24 (45.3) |
| Bleeding more days | 56 (52.8) | 87 (47.0) | 2 (20.0) | 13 (24.5) |
| Bleeding fewer days | 20 (18.9) | 36 (19.5) | 2 (20.0) | 21 (39.6) |
| Pelvic pain >6 mo affecting normal function | ||||
| No | 106 (55.8) | 184 (65.2) d | 13 (92.9) | 102 (90.3) |
| Yes | 84 (44.2) | 98 (34.8) | 1 (7.1) | 11 (9.7) |
| Painful menses cramps >6 mo b | ||||
| No | 91 (49.2) | 179 (66.8) e | 12 (92.3) | 98 (89.9) |
| Yes; specify duration, mo | 94 (50.8) | 89 (33.2) | 1 (7.7) | 11 (10.1) |
| <6 | 8 (6.8) | 6 (4.7) | 1 (50.0) | 2 (10.5) |
| 6-12 | 24 (20.3) | 31 (24.4) | 0 (0.0) | 1 (5.3) |
| 13-24 | 25 (21.2) | 20 (15.8) | 1 (50.0) | 3 (15.8) |
| >24 | 61 (51.7) | 70 (55.1) | 0 (0.0) | 13 (68.4) |
b Among women with ≥1 menstrual cycles in past 12 mo;
Logistic regression identified only one consistent risk factor across both cohorts–a history of infertility ( Table 3 ). An infertility history increased the odds of an endometriosis diagnosis >2-fold in the operative cohort (adjusted odds ratio [AOR], 2.43; 95% CI, 1.57−3.76), and >7-fold in the population cohort (AOR, 7.91; 95% CI, 1.69−37.2), even after adjusting for age and study site. Other risk factors either decreased or increased the odds of an endometriosis diagnosis in the operative cohort only, as follows ( Table 3 ). Specifically, odds were decreased for gravidity (AOR, 0.49; 95% CI, 0.32−0.75), parity (AOR, 0.42; 95% CI, 0.28−0.64), and BMI (AOR, 0.95; 95% CI, 0.93−0.98). Factors that increased the odds of diagnosis included: college education (AOR, 1.83; 95% CI, 1.12−3.00), older age at first sex (AOR, 1.06; 95% CI, 1.01−1.12), pelvic pain as a surgical indication for laparoscopy (AOR, 3.67; 95% CI, 2.44−5.50), and dysmenorrhea (OR, 2.46; 95% CI, 1.28−4.72). We found no relationship to endometriosis for any aspect of menstrual history other than dysmenorrhea in either cohort.
| Risk factor | Operative cohort (n = 473) | Population cohort (n = 127) | ||
|---|---|---|---|---|
| Unadjusted OR (95% CI) | Adjusted a OR (95% CI) | Unadjusted OR (95% CI) | Adjusted a OR (95% CI) | |
| Sociodemographic | ||||
| Age, y | 0.97 (0.94–0.99) | — | 1.02 (0.95–1.09) | — |
| Above poverty level (yes/no) b | 1.53 (0.83–2.80) | 1.88 (1.00–3.52) | 0.86 (0.17–4.24) | 0.87 (0.17–4.53) |
| College educated (yes/no) | 1.63 (1.00–2.64) | 1.83 (1.12–3.00) | 0.58 (0.11–2.98) | 0.58 (0.11–3.13) |
| Reproductive history | ||||
| Gravid (vs nulligravid) | 0.48 (0.33–0.71) | 0.49 (0.32–0.75) | 1.24 (0.39–3.93) | 1.02 (0.27–3.78) |
| Parous (vs nulliparous) | 0.47 (0.32–0.68) | 0.42 (0.28–0.64) | 1.31 (0.43–4.02) | 1.06 (0.28–3.96) |
| Infertility history (yes/no) | 2.49 (1.61–3.83) | 2.43 (1.57–3.76) | 7.13 (1.72–29.6) | 7.91 (1.69–37.2) |
| Age at first consenting sex, y | 1.05 (1.00–1.11) | 1.06 (1.01–1.12) | 1.07 (0.88–1.29) | 1.05 (0.87–1.28) |
| Surgical indication for laparoscopy (pelvic pain vs other) | 3.91 (2.65–5.76) | 3.67 (2.44–5.50) | — | — |
| Menstruation (past 12 mo) | ||||
| Age at menarche, y | 1.06 (0.95–1.18) | 1.05 (0.94–1.17) | 1.27 (0.87–1.87) | 1.25 (0.84–1.85) |
| Mean no. of periods c | 0.99 (0.95–1.02) | 0.99 (0.96–1.02) | 0.99 (0.91–1.08) | 0.99 (0.91–1.07) |
| Mean cycle length, d c | 0.99 (0.98–1.00) | 0.99 (0.98–1.00) | 0.95 (0.85–1.06) | 0.95 (0.85–1.06) |
| Mean length shortest cycle, d c | 0.99 (0.98–1.00) | 0.99 (0.98–1.00) | 1.02 (0.98–1.06) | 1.02 (0.98–1.06) |
| Mean length longest cycle, d c | 0.99 (0.99–1.00) | 0.99 (0.99–1.00) | 1.01 (0.98–1.04) | 1.01 (0.99–1.04) |
| Dysmenorrhea (yes/no) | 2.78 (1.46–5.29) | 2.46 (1.28–4.72) | 1.37 (0.28–6.58) | 1.41 (0.28–7.14) |
| Pelvic pain (yes/no) | 0.95 (0.93–0.98) | 1.39 (0.95–2.04) | 1.01 (0.93–1.09) | 0.76 (0.09–6.54) |
| Body mass index, kg/m 2 | 0.95 (0.93–0.98) | 0.95 (0.93–0.98) | 1.01 (0.93–1.09) | 1.01 (0.93–1.09) |
a Adjusted for age (y) and site;
b Based upon 2007 Health and Human Services Poverty Guidelines accounting for numbers of persons in household for 48 contiguous states and District of Columbia;
Multiple sensitivity analyses assessed the robustness of our findings. As summarized in Tables 4-7 , infertility was a consistent risk factor across all analyses irrespective of cohort. When restricting to histologically confirmed endometriosis ( Table 4 ) and endometriosis stages 3 and 4 ( Table 5 ), college education and history of pelvic pain were not significant. Dysmenorrhea (AOR, 3.11; 95% CI, 0.94−10.3) was not significant in the model restricted to histologically confirmed disease ( Table 4 ). The effect for BMI (AOR, 0.97; 95% CI, 0.93−1.01) was nonsignificant, but the effects for parity (AOR, 0.19; 95% CI, 0.10−0.37), age at first sex (AOR, 1.11; 95% CI, 1.03−1.19), and surgical indication (AOR, 4.47; 95% CI, 2.39−8.38) were significant when restricting endometriosis to stages 3 and 4 in the operative cohort (11.8%, or 56/473 of the operative cohort) ( Tables 4 and 5 ). All of the previously noted risk factors were significantly associated with endometriosis when restricting the comparison group in the operative cohort to women with a surgically visualized normal pelvis ( Table 6 ). In the population cohort, 11% (14/127) of women were diagnosed with probable moderate/severe endometriosis detected with MRI compared to 11.8% (56/473) in the operative cohort. Significant differences across both cohorts and in all sensitivity analyses are summarized in Table 7 .
