Incident Endometriosis Research Articles

Examining the co-occurrence of endometriosis and polycystic ovarian syndrome

Polycystic ovarian syndrome and endometriosis are 2 of the most common reproductive disorders among women but are thought to be unrelated. This study aimed to examine the overlap and common symptoms of polycystic ovarian syndrome and endometriosis. The study population included the Endometriosis, Natural History, Diagnosis, and Outcomes Study (2007-2009) operative cohort: 473 women, aged 18 to 44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of 14 surgical centers located in Salt Lake City, Utah, or San Francisco, California, in addition to a population cohort composed of 127 women from the surgical centers' catchment areas. Age and site-adjusted multinomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals of reproductive history characteristics among women with endometriosis only, women with polycystic ovarian syndrome only, and women with both endometriosis and polycystic ovarian syndrome. Among the operative cohort, 35% had endometriosis only, 9% had polycystic ovarian syndrome only, and 5% had endometriosis and polycystic ovarian syndrome. Among the population cohort, 10% had endometriosis only, 8% had polycystic ovarian syndrome only, and 2% had endometriosis and polycystic ovarian syndrome. In the operative cohort, a history of subfertility was associated with a higher adjusted probability of having both conditions (adjusted prevalence ratio, 10.33; 95% confidence interval, 3.94-27.08), followed by having endometriosis only (adjusted prevalence ratio, 2.45; 95% confidence interval, 1.56-3.84) or polycystic ovarian syndrome only (adjusted prevalence ratio, 1.15; 95% confidence interval, 0.51-2.61), than having neither condition. In addition, experiencing chronic pelvic pain within the past 12 months was associated with a higher probability of having both conditions (adjusted prevalence ratio, 2.53; 95% confidence interval, 1.07-6.00) than having neither condition. Among a cohort of women undergoing gynecologic laparoscopy or laparotomy, our study found that nearly 1 in 20 women had both an incident endometriosis diagnosis and symptoms consistent with polycystic ovarian syndrome. Among a population cohort of women not seeking gynecologic care, polycystic ovarian syndrome and endometriosis overlap prevalence was approximately 1 in 50 women.

Endogenous Steroid Hormone Concentrations and Risk of Endometriosis in Nurses' Health Study II.

Few studies have assessed the association between endogenous steroid hormone levels and a subsequent diagnosis of endometriosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically confirmed endometriosis in a nested case-control study within Nurses' Health Study II. Between blood collection (1996-1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RRs) and 95% confidence intervals (CIs). Women with greater early follicular-phase total or free estradiol levels had a nonlinear increased risk of endometriosis (early follicular total estradiol: second quartile vs. first, RR=2.23 (95% CI: 1.44, 3.47); third quartile, RR=1.83 (95% CI: 1.16, 2.88); fourth quartile, RR=1.68 (95% CI: 1.05, 2.68); early follicular free estradiol: second quartile vs. first, RR=1.63 (95% CI: 1.05, 2.54); third quartile, RR=2.02 (95% CI: 1.31, 3.12); fourth quartile, RR=1.04 (95% CI: 0.66, 1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed, with a positive association among women in the top 2% of free testosterone levels. Levels of mid-luteal-phase total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects.

Hydroxychloroquine might reduce risk of incident endometriosis in patients with systemic lupus erythematosus: A retrospective population-based cohort study

SLE, which is common in women, is commonly treated with HCQ, an anti-inflammation medication. Reproductive-age women with SLE are prone to be impacted by endometriosis. This study analyzes the relationship between HCQ and endometriosis patients with SLE in order to determine whether HCQ is effective for treating the latter. This population-based, retrospective cohort study analyzed the SLE risk in a cohort of newly diagnosed SLE patients with endometriosis during 2000 through 2013. Controls were selected at a 1:2 ratio through age-matching using the greedy algorithm. The Cox proportional hazard model was used to analyze the association between HCQ use and endometriosis incidence. Four different Cox regression models were used. Lastly, sensitivity analysis with PSOW and IPW was implemented to evaluate the hazard ratio (HR) of endometriosis after exposure with HCQ. In the cohort where age and sex matched high and low HCQ dosage, the average follow-up time was about 1 year. The cohort's overall incidence rates of endometriosis were 44.54 and 90.03 per 100000 person-month for high and low dosage respectively. The high dose group's conditional hazard ratio (aHR) for incidental endometriosis was 0.482 (CI = 0.191 to 1.213). The incidence rate and Kaplan-Meir curves of endometriosis were consistent with the results for the cohort. This study demonstrated that SLE patients continuously treated with HCQ have a lower risk of developing endometriosis. Clinically, HCQ can be beneficial for endometriosis patients with SLE.

Endometriosis and New-Onset Coronary Artery Disease in Taiwan: A Nationwide Population-Based Study.

Endometriosis (EM) with chronic inflammation may accelerate the progression of atherosclerosis. Currently, no large or randomized clinical studies have assessed the incidence of cardiovascular events in patients with endometriosis in Asia to investigate whether incident EM is associated with a higher risk of new-onset coronary artery disease (CAD). In this study of a nationwide cohort in Taiwan, we identified 13,988 patients with newly diagnosed EM from 1 January, 2000, through 31 December, 2012. EM and non-EM groups were matched by propensity score at a ratio of 1:1. Of a total 27,976 participants, 358 developed CAD. The incidence rate in the EM group was higher than that in the non-EM group (1.8 per 1,000 person-years vs. 1.3 per 1,000 person-years) during the follow-up period. The adjusted hazard ratio (aHR) of CAD for the EM group was 1.52 with a 95% confidence interval (1.23–1.87, p < 0.001) after adjusting for demographic characteristics, comorbidities, surgical procedures, frequency of outpatient visits, and medications. Stratified analysis revealed that, among four age groups (20–39, 40–49, 50–54, and above 55 years), the 20–39 years sub-group was associated with a higher risk of CAD (aHR, 1.73; 95% CI, 1.16–2.59, p = 0.008). Several sensitivity analyses were conducted for cross-validation, and it showed consistent positive findings. In conclusion, this cohort study revealed that patients with symptomatic EM in Taiwan were associated with increased risk of subsequent CAD than patients without medical records of EM. Further prospective studies are needed to confirm this causal relationship.

Incidence, prevalence, and trends in endometriosis diagnosis: a United States population-based study from 2006 to 2015

Accurate estimates of incidence and prevalence of endometriosis among nonselected cohorts are lacking in the United States, and earlier reports have produced varying results. This study aimed to define endometriosis incidence and prevalence in a US population and evaluate factors influencing these estimates over time. A 10-year retrospective cohort study using Kaiser Permanente Washington electronic health records database was completed. The primary analysis included women enrollees aged 16 to 60 years, from January 2006 to December 2015, who had a uterus, were continuously enrolled for at least 2 years before cohort entry and had at least 1 healthcare utilization. Secondary analysis included all women enrollees aged 16 to 60 years during this time. Incident endometriosis was identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes. Annual incidence rates were age-adjusted by direct standardization to the 2015 study population. Secular trends in incidence overall and by 5-year age group, race and ethnicity, diagnosis modality, and practitioner type were assessed using Poisson regression analyses. Prevalent cases were defined as women enrolled in 2015 and had an endometriosis diagnosis before the end of 2015. The prevalence rates of chronic pelvic pain and dysmenorrhea defined by the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes in 2006-2015 were estimated. Among 332,056 eligible women who contributed 1,176,329 person-years during the 10-year study period, 2863 incident endometriosis cases were identified for an average incidence of 24.3 cases per 10,000 person-years. In our primary analysis, incidence rates declined over the study interval from a high of 30.2 per 10,000 person-years in 2006 to 17.4 per 10,000 person-years in 2015 and were highest among women aged 36 to 45 years in most years. Incidence rates were similar across race and ethnicity groups. The distribution of the 2863 incident cases by the diagnosis modality was as follows: 45.5% surgical, 5.7% imaging, and 48.8% clinical. Endometriosis incidence rates per 10,000 person-years were similar in women who were surgically and clinically diagnosed and decreased significantly from 2006 to 2015 (surgically diagnosed endometriosis dropped from 13.4 to 7.4 and clinically diagnosed endometriosis dropped from 16.1 to 8.9; P value of <.001 for linear trend over time for each). Incident case distribution by diagnosing provider was as follows: 73.6% obstetrician and gynecologist, 15.7% primary care provider, and 10.7% "other." Incidence of endometriosis diagnosed by an obstetrician and gynecologist and primary care provider decreased over the study interval (P<.001 for linear trend over time for each). Method of diagnosis and provider type did not differ by race and ethnicity. Among 135,162 women who contributed person-time in 2015, 2521 women were diagnosed with endometriosis, a prevalence rate of 1.9%. In our secondary analysis, the frequency of chronic pelvic pain diagnosis increased over the study interval from 3.0% in 2006 to 5.6% in2015. The incidence rates of endometriosis declined over the 10-year study interval and did so uniformly across age groups, races and ethnicities, and the main diagnosing modalities and providers. Declining rates may reflect a shift in practice patterns in the United States away from the diagnosis of endometriosis both clinically and surgically, rather than favoring more general diagnoses of chronic pelvic pain. The prevalence of endometriosis in 2015 in the United States is in keeping with data from recent studies outside the United States using health record data.

Adipose to serum ratio and mixtures of persistent organic pollutants in relation to endometriosis: Findings from the ENDO Study

BackgroundEndometriosis is an estrogen-dependent disease. Endocrine disrupting chemicals (EDCs) and their mixtures may play an etiologic role. ObjectivesWe evaluated an adipose-to-serum ratio (ASR) of lipophilic EDCs and their mixtures associated with incident endometriosis. MethodsWe quantified 13 polychlorinated biphenyl (PCB) congeners, 6 polybrominated diphenyl ether (PBDE) congeners, and 11 organochlorine pesticides (OCPs) in serum and omental fat among women from the ENDO Study (2007–2009) aged 18–44 years diagnosed with (n=190) or without (n=283) surgically-visualized incident endometriosis. Odds ratios (OR) and 95% confidence intervals (CI) between ASR and endometriosis were estimated using logistic regression models adjusted for age (years), body mass index (kg/m2), serum cotinine (ng/ml), and breastfeeding conditional on parity. Bayesian hierarchical models (BHM) compared estimated associations for adipose and ASR to serum. Bayesian kernel machine regression (BKMR) estimated change in latent health and 95% posterior intervals (PI) between chemical mixtures and endometriosis. ResultsSelect ASR for estrogenic PCBs and OCPs were associated with an increased odds of an endometriosis diagnosis, but not for anti-estrogenic PCBs or PBDEs. Across all chemicals, BHMs generated ORs that were on average 14% (95% PI: 6%, 22%) higher for adipose and 20% (95% PI: 12%, 29%) higher for ASR in comparison to serum. ORs from BHMs were greater for estrogenic PCBs and OCPs, with no differences for PBDEs. BKMR models comparing the 75th to 25th percentile were moderately associated with endometriosis for estrogenic PCBs [adipose 0.27 (95% PI: 0.18, 0.72) and ASR 0.37 (95% PI: 0.06, 0.80)] and OCPs [adipose 0.17 (95% PI: 0.21, 0.56) and ASR 0.26 (95% PI: 0.05, 0.57)], but not for antiestrogenic PCBs and PBDEs. DiscussionASR added little insight beyond adipose for lipophilic chemicals. BKMR results supported associations between ASR and adipose estrogenic PCB and OCP mixtures and incident endometriosis. These findings underscore the importance of choice of biospecimen and considering mixtures when assessing exposure-disease relationships.

Adiposity and Endometriosis Severity and Typology

Prior research has collectively shown that endometriosis is inversely related to women's adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology. Cross-sectional study among women with no prior diagnosis of endometriosis. Fourteen clinical centers in Salt Lake City, UT, and San Francisco, CA. A total of 495 women (of which 473 were analyzed), aged 18-44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. Gynecologic laparoscopy/laparotomy regardless of clinical indication. Participants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I-IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I-IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators. Our research highlights that the relationship between women's adiposity and endometriosis severity and typology may be more complicated than prior research indicates.

Risk of Endometriosis and Subsequent Ovary and Breast Cancers in Nurses: A Population-Based Cohort Study in Taiwan.

Background: Endometriosis has been associated with the subsequent development of ovarian and breast cancers. This study evaluated whether nurses were at increased risks of developing endometriosis and subsequent ovarian and breast cancers. Methods: From Taiwan National Health Insurance Research Database during 2000 to 2011, we established 3 study cohorts, consisting of 23,801 nurses, 11,973 other hospital employees, and 143,096 general women free of endometriosis and cancer. Women in all cohorts were followed to the end of 2011 to measure the occurrences of endometriosis and subsequent ovarian and breast cancers. The incident endometriosis cases and related hazard ratio (HR) and 95% confidence interval (CI) were calculated. The incident cases of ovarian cancer and breast cancer and related odds ratio were calculated. Results: The incidence of endometriosis was the highest in the nurse cohort (4.23 per 100, n = 966) followed by other health professionals (3.74 per 100, n = 427) and control cohort (3.06 per 100, n = 4193), with adjusted hazard ratios of 1.28 (95% CI = 1.20–1.38) and 1.13 (95% CI = 1.02–1.25), respectively, comparing to controls. Among those who developed endometriosis, nurses had higher subsequent ovarian cancer and lower breast cancer, but not significant. Conclusions: Nurses are at a higher risk of developing endometriosis. However, the link between endometriosis and subsequent cancers is weak.

Modifiable life style factors and risk for incident endometriosis.

Caffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone-dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis. Four hundred and seventy three women, ages 18-44years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007-2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors. There were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk. This study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.

Risk of Developing Comorbidities Among Women with Endometriosis: A Retrospective Matched Cohort Study

Endometriosis has been associated with higher rates of various chronic conditions, but its epidemiological data are fragmented and dated. We sought to compare the incidence of developing commonly occurring comorbidities among patients with and without endometriosis in a large, contemporary patient cohort that reflects real-world clinical practice. A cohort of women aged 18-49 with incident endometriosis was extracted from the 2006-2015 de-identified Clinformatics® DataMart commercial insurance claims database (OptumInsight, Eden Prairie, MN). Endometriosis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 617.x on ≥1 inpatient or emergency department claim or ≥2 outpatient claims. Nonendometriosis control patients were exactly matched 4:1 to cases based on state, insurance plan type, and age (±1 year). Based on a literature review and expert consultation, 22 comorbidities were identified for analysis. The risk of developing a comorbidity post-index date was analyzed with stratified Cox proportional hazards models. There were 26,961 cases and 107,844 controls. Mean age was 36 years. The adjusted risk of developing a comorbid condition among endometriosis cases was statistically significantly higher than the matched controls for all 22 comorbidities (p ≤ 0.001) and was at least twice as large for nine comorbidities (infertility/subfertility, ovarian cyst, uterine fibroids, pelvic inflammatory disorder, interstitial cystitis, irritable bowel syndrome, constipation/dyschezia, ovarian cancer, and endometrial cancer). The incidence of developing many comorbidities was significantly higher among endometriosis patients compared with matched women without endometriosis. Additional research is needed to establish the implications for healthcare resource use.

History of breast feeding and risk of incident endometriosis: prospective cohort study

Objective To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women.Design Prospective cohort study.Setting Nurses’ Health Study II, 1989-2011.Participants 72...

A Prospective Study of Inflammatory Markers and Risk of Endometriosis.

Much evidence suggests a role for inflammation in the pathogenesis of endometriosis. Although investigators in numerous case-control studies have found elevation of inflammatory markers in patients with endometriosis, results were not consistent, and no prior prospective study is known to exist. We conducted a case-control study nested within the Nurses' Health Study II in which we examined associations between levels of plasma inflammatory markers (interleukin-1 beta, interleukin-6, soluble tumor necrosis factor α receptors 1 and 2, and high-sensitivity C-reactive protein) and the risk of laparoscopically confirmed endometriosis. From blood collections in 1996-1999 and 2007, we ascertained 350 cases patients with incident endometriosis and 694 matched controls. Women with interleukin-1 beta levels in quintiles 2-4 had a higher risk of endometriosis (for the second quintile, relative risk (RR) = 3.30, 95% confidence interval (CI): 1.06, 10.3; for the third quintile, RR = 3.36, 95% CI: 1.09, 10.4; and for the fourth quintile, RR = 4.64, 95% CI: 1.58, 13.6; P for trend = 0.62), which suggested an association beginning at 0.47 pg/mL or greater. A significant nonlinear association with levels of soluble tumor necrosis factor α receptor 2 was observed, with elevated risk of endometriosis at concentrations greater than 3,400 pg/mL. Plasma interleukin-6, soluble tumor necrosis factor α receptor 1, and high-sensitivity C-reactive protein levels were not associated with endometriosis risk. Further research in larger studies with younger age at blood collection and longer time from blood to surgical diagnosis are required to confirm these associations.

Urinary Phytoestrogen Concentrations Are Not Associated with Incident Endometriosis in Premenopausal Women

BackgroundPhytoestrogens have been associated with subtle hormonal changes, but their effects on endometriosis are largely unknown. ObjectiveWe assessed the association between urinary concentrations of phytoestrogens and incident endometriosis. MethodsWe included an operative sample of 495 premenopausal women aged 18–44 y undergoing laparoscopies and laparotomies at 14 clinical sites between 2007 and 2009 and a general population sample of 131 women from the same geographic area who were matched on age and menstruation status. Endometriosis in the surgical sample was assessed by surgical visualization (clinical gold standard), whereas disease in the general population sample was assessed with the use of a pelvic MRI. Urine concentrations of genistein, daidzen, O-desmethylangolensin, equol, enterodiol, and enterolactone were measured at baseline. Poisson regression with robust error variance was used to estimate the risk of an endometriosis diagnosis for each sample after adjusting for age and body mass index (in kg/m2). Separate models were run for each phytoestrogen. ResultsOverall geometric mean urine concentrations of phytoestrogens were as follows: genistein [88 nmol/L (95% CI: 72, 108 nmol/L)], daidzein [194 nmol/L (95% CI: 160, 236 nmol/L)], O-desmethylangolensin [4 nmol/L (95% CI: 3, 6 nmol/L)], equol [4 nmol/L (95% CI: 4, 6 nmol/L)], enterodiol [29 nmol/L (95% CI: 22, 38 nmol/L)], and enterolactone [355 nmol/L (95% CI: 395, 544 nmol/L)]. Geometric mean concentrations of phytoestrogens did not significantly differ by endometriosis status in either sample. Adjusted RRs for endometriosis ranged from 0.87 to 1.09 for the 6 phytoestrogens measured, with all CIs including a value ≥1. Phytoestrogens were not associated with the severity of endometriosis when restricting the analysis to women with moderate-to-severe disease per the revised American Society for Reproductive Medicine criteria. Furthermore, no associations were observed between self-reported high soy intake and endometriosis. ConclusionsDespite endometriosis being an estrogen-dependent disease, we found no evidence that urinary phytoestrogens were associated with a higher risk of an endometriosis diagnosis in either a sample of premenopausal women or in a surgical sample.

Women's Reproductive History Before the Diagnosis of Incident Endometriosis.

Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs <1.0 denote a longer TTP or diminished fecundity. Approximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ≈29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently <1.0, irrespective of endometriosis staging, CIs included 1. Women with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment.

Sexual and physical abuse and gynecologic disorders

Is sexual and/or physical abuse history associated with incident endometriosis diagnosis or other gynecologic disorders among premenopausal women undergoing diagnostic and/or therapeutic laparoscopy or laparotomy regardless of clinical indication? No association was observed between either a history of sexual or physical abuse and risk of endometriosis, ovarian cysts or fibroids; however, a history of physical abuse was associated with a higher likelihood of adhesions after taking into account important confounding and mediating factors. Sexual and physical abuse may alter neuroendocrine-immune processes leading to a higher risk for endometriosis and other noninfectious gynecologic disorders, but few studies have assessed abuse history prior to diagnosis. The study population for these analyses includes the ENDO Study (2007-2009) operative cohort: 473 women, ages 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of the 14 surgical centers located in Salt Lake City, UT, USA or San Francisco, CA, USA. Women with a history of surgically confirmed endometriosis were excluded. Prior to surgery, women completed standardized abuse questionnaires. Relative risk (RR) of incident endometriosis, uterine fibroids, adhesions or ovarian cysts by abuse history were estimated, adjusting for age, race/ethnicity, education, marital status, smoking, gravidity and recruitment site. We assessed whether a history of chronic pelvic pain, depression, or STIs explained any relationships via mediation analyses. 43 and 39% of women reported experiencing sexual and physical abuse. No association was observed between either a history of sexual or physical abuse, versus no history, and risk of endometriosis (aRR: 1.00 [95% confidence interval (CI): 0.80-1.25]); aRR: 0.83 [95% CI: 0.65-1.06]), ovarian cysts (aRR: 0.67 [95% CI: 0.39-1.15]); aRR: 0.60 [95% CI: 0.34-1.09]) or fibroids (aRR: 1.25 [95% CI: 0.85-1.83]); aRR: 1.36 [95% CI: 0.92-2.01]). Conversely, a history of physical abuse, versus no history, was associated with higher risk of adhesions (aRR: 2.39 [95% CI: 1.18-4.85]). We found no indication that the effect of abuse on women's adhesion risk could be explained by a history of chronic pelvic pain, depression or STIs. Limitations to our study include inquiries on childhood physical but not sexual abuse. Additionally, we did not inquire about childhood or adulthood emotional support systems, found to buffer the negative impact of stress on gynecologic health. Abuse may be associated with some but not all gynecologic disorders with neuroendocrine-inflammatory origin. High prevalence of abuse reporting supports the need for care providers to screen for abuse and initiate appropriate follow-up. Supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001406-02). The authors have no potential competing interests.

Pain typology and incident endometriosis.

What are the pain characteristics among women, with no prior endometriosis diagnosis, undergoing laparoscopy or laparotomy regardless of clinical indication? Women with surgically visualized endometriosis reported the highest chronic/cyclic pain and significantly greater dyspareunia, dysmenorrhea, and dyschezia compared with women with other gynecologic pathology (including uterine fibroids, pelvic adhesions, benign ovarian cysts, neoplasms and congenital Müllerian anomalies) or a normal pelvis. Prior research has shown that various treatments for pain associated with endometriosis can be effective, making identification of specific pain characteristics in relation to endometriosis necessary for informing disease diagnosis and management. The study population for these analyses includes the ENDO Study (2007-2009) operative cohort: 473 women, ages 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at one of 14 surgical centers located in Salt Lake City, UT or San Francisco, CA. Women with a history of surgically confirmed endometriosis were excluded. Endometriosis was defined as surgically visualized disease; staging was based on revised American Society for Reproductive Medicine (rASRM) criteria. All women completed a computer-assisted personal interview at baseline specifying 17 types of pain (rating severity via 11-point visual analog scale) and identifying any of 35 perineal and 60 full-body front and 60 full-body back sites for which they experienced pain in the last 6 months. There was a high prevalence (≥30%) of chronic and cyclic pelvic pain reported by the entire study cohort regardless of post-operative diagnosis. However, women with a post-operative endometriosis diagnosis, compared with women diagnosed with other gynecologic disorders or a normal pelvis, reported more cyclic pelvic pain (49.5% versus 31.0% and 33.1%, P < 0.001). Additionally, women with endometriosis compared with women with a normal pelvis experienced more chronic pain (44.2 versus 30.2%, P = 0.04). Deep pain with intercourse, cramping with periods, and pain with bowel elimination were much more likely reported in women with versus without endometriosis (all P < 0.002). A higher percentage of women diagnosed with endometriosis compared with women with a normal pelvis reported vaginal (22.6 versus 10.3%, P < 0.01), right labial (18.4 versus 8.1%, P < 0.05) and left labial pain (15.3 versus 3.7%, P < 0.01) along with pain in the right/left hypogastric and umbilical abdominopelvic regions (P < 0.05 for all). Among women with endometriosis, no clear and consistent patterns emerged regarding pain characteristics and endometriosis staging or anatomic location. Interpretation of our findings requires caution given that we were limited in our assessment of pain characteristics by endometriosis staging and anatomic location due to the majority of women having minimal (stage I) disease (56%) and lesions in peritoneum-only location (51%). Significance tests for pain topology related to gynecologic pathology were not corrected for multiple comparisons. Results of our research suggest that while women with endometriosis appear to have higher pelvic pain, particularly dyspareunia, dysmenorrhea, dyschezia and pain in the vaginal and abdominopelvic area than women with other gynecologic disorders or a normal pelvis, pelvic pain is commonly reported among women undergoing laparoscopy, even among women with no identified gynecologic pathology. Future research should explore causes of pelvic pain among women who seek out gynecologic care but with no apparent gynecologic pathology. Given our and other's research showing little correlation between pelvic pain and rASRM staging among women with endometriosis, further development and use of a classification system that can better predict outcomes for endometriosis patients with pelvic pain for both surgical and nonsurgical treatment is needed. Supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001406-02). The authors have no potential competing interests.

A prospective study of insulin-like growth factor 1, its binding protein 3, and risk of endometriosis.

Several retrospective case-control studies suggested that insulin-like growth factor 1 (IGF-1) or insulin-like growth factor binding protein 3 (IGFBP-3) was associated with endometriosis. However, results are inconsistent and no prospective study exists. We prospectively evaluated associations between plasma levels of IGF-1 and IGFBP-3 and laparoscopically confirmed endometriosis in a case-control study nested within the Nurses' Health Study II. Between blood collections in 1996-1999 and 2007, we ascertained 310 premenopausal women with incident endometriosis and 615 matched controls. We estimated incidence rate ratios and 95% confidence intervals using multivariable conditional logistic regression. We observed no statistically significant associations between endometriosis and IGF-1 (incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.61, 1.27; Ptrend = 0.48), IGFBP-3 (IRR = 1.12, 95% CI: 0.80, 1.57; Ptrend = 0.51), and the IGF-1:IGFBP-3 molar ratio (IRR = 0.94, 95% CI: 0.66, 1.34; Ptrend = 0.64), comparing the top with the bottom tertile. IGF-1, IGFBP-3, and the molar ratio appeared to be positively associated with endometriosis risk among women aged <40 years at blood draw (IGF-1: IRR = 1.60, 95% CI: 0.86, 2.98; IGFBP-3: IRR = 1.85, 95% CI: 1.08, 3.16; IGF-1:IGFBP-3: IRR = 1.57, 95% CI: 0.85, 2.88) but not among women aged ≥40 years at blood draw (all Pheterogeneity ≤ 0.05). Overall, these data suggest that, if IGF-1 or IGFBP-3 plays a role in the etiology of endometriosis, it is minimal and perhaps only among younger women.

Vitamin D and female fertility

Apart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes. We will review the most interesting and relevant studies on vitamin D and female fertility published over the past year. In the past year, several observational studies reported a better in-vitro fertilization outcome in women with sufficient vitamin D levels (≥30 ng/ml), which was mainly attributed to vitamin D effects on the endometrium. One randomized controlled trial found an increased endometrial thickness in women with polycystic ovary syndrome (PCOS) receiving vitamin D during intrauterine insemination cycles. Further, vitamin D supplementation had a beneficial effect on serum lipids in PCOS women. Vitamin D treatment improved endometriosis in a rat model and increased vitamin D intake was related to a decreased risk of incident endometriosis. Vitamin D was also favorably associated with primary dysmenorrhea, uterine leiomyoma, and ovarian reserve in late reproductive aged women. In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥30 ng/ml) should be obtained. Vitamin D supplementation might improve metabolic parameters in women with PCOS. A high vitamin D intake might be protective against endometriosis.

Air Pollution Exposures During Adulthood and Risk of Endometriosis in the Nurses’ Health Study II

Background: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis.Objective: Our goal was to determine the association of air pollution exposures during adulthood, including distance to road, particulate matter < 2.5 μm, between 2.5 and 10 μm, and < 10 μm, (PM2.5, PM10–2.5, PM10), and timing of exposure with risk of endometriosis in the Nurses’ Health Study II.Methods: Proximity to major roadways and outdoor levels of PM2.5, PM10–2.5, and PM10 were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk.Results: Among 84,060 women, 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association between endometriosis risk and distance to road or exposure to PM2.5, PM10–2.5, or PM10 averaged over follow-up or during the previous 2- or 4-year period.Conclusions: Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women.Citation: Mahalingaiah S, Hart JE, Laden F, Aschengrau A, Missmer SA. 2014. Air pollution exposures during adulthood and risk of endometriosis in the Nurses’ Health Study II. Environ Health Perspect 122:58–64; http://dx.doi.org/10.1289/ehp.1306627

In utero exposures and incident endometriosis, the ENDO study

Growing evidence suggests that endometriosis may arise in utero in keeping with the early origins of health and disease hypothesis. In response, we assessed various in utero exposures in relation to the incidence of visualized endometriosis in a cohort of women undergoing surgery.