Lifestyle and Environment · Substances
Wolff EF, Sun L, Hediger ML, Sundaram R, Peterson CM, Chen Z, Buck Louis GM
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To assess in utero exposures and the odds of an endometriosis diagnosis.
Matched cohort design.
Fourteen participating clinical centers in geographically defined areas in Utah and California.
Operative cohort comprised 473 women undergoing laparoscopy/laparotomy, and an age- and residence-matched population cohort comprising 127 women undergoing pelvic magnetic resonance imaging (MRI), 2007-2009.
None.
Women completed standardized interviews before surgery or MRI regarding in utero exposures: mothers' lifestyle during the index pregnancy, and the index woman's gestation and birth size. Endometriosis was defined as visually confirmed disease in the operative cohort, and MRI visualized disease in the population cohort. The odds of an endometriosis diagnosis and corresponding 95% confidence intervals (CI) were estimated for each exposure by cohort using logistic regression and adjusting for current smoking, age at menarche, body mass index, and study site.
Endometriosis was diagnosed in 41% and 11% of women in the operative and population cohorts, respectively. In the primary analysis, adjust odds ratios (AORs) were elevated for maternal vitamin usage (1.27; 95% CI, 0.85-1.91), maternal cigarette smoking (1.16; 95% CI = 0.61-2.24), and low birth weight (1.1; 95% CI, 0.92-1.32). Reduced odds were observed for maternal usage of caffeine (0.99; 95% CI, 0.64-1.54), alcohol (0.82; 95% CI, 0.35-1.94), paternal cigarette smoking (0.72; 95% CI, 0.43-1.19), and preterm delivery (0.98; 95% CI, 0.47-2.03). Sensitivity analyses mostly upheld the primary results except for a decreased AOR for preterm birth (0.41; 95% CI, 0.18-0.94) when restricting to visualized and histologically confirmed endometriosis in the operative cohort.
In utero exposures were not statistically significantly associated with the odds of an endometriosis diagnosis in either cohort.
Schliep KC et al., 2026 · J Gynecol Obstet Hum Reprod · Free full text on PubMed Central
Endometriosis has been linked to cardiometabolic alterations, but whether these associations vary by disease severity or phenotype is unclear. We examined lipid profiles across endometriosis diagnosis, stage, and typology. Data came from 476 women in the NICHD ENDO cohort. Endometriosis was confirmed laparoscopically and staged using the rASRM criteria (I-IV). Typology was categorized as superficial endometriosis (SE), ovarian endometrioma (OE), deep infiltrating endometriosis (DE), and OE+DE. We compared endometriosis status, stage (I/II vs III/IV), and typology to no endometriosis using adverse lipid thresholds (total cholesterol ≥200 mg/dL, HDL <50 mg/dL, LDL ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, ApoA1 <125 mg/dL, and ApoB ≥120 mg/dL). Adjusted prevalence ratios (aPR) and 95 % CIs were estimated via generalized linear models, controlling for age, race/ethnicity, BMI, income, marital status, and serum cotinine. Endometriosis diagnosis alone was not associated with adverse lipid profiles. In contrast, moderate/severe disease showed higher prevalence of elevated triglycerides (aPR= 2.27; 95 % CI: 1.18,4.35) and VLDL (aPR= 2.41; 95 % CI: 1.50, 3.85). Typology revealed stronger patterns: OE and OE+DE were associated with adverse profiles across multiple markers (aPRs 1.59-4.09), particularly ApoB and triglycerides. Minimal/mild disease and SE were not associated. The metabolic signal was phenotype-driven rather than diagnosis-driven, with severe stage and OE/OE+DE showing clear associations with adverse lipid profiles. These findings suggest lipid profiles may serve as markers of phenotype severity or shared biological milieu. Replication in larger cohorts is needed.
Valenti M et al., 2026 · Am J Obstet Gynecol · Free full text on PubMed Central
Endometriosis is a chronic, gynecologic condition in which tissue similar to the lining of the uterus implants throughout the body. Women with endometriosis have a higher prevalence of infertility and a greater risk of early natural menopause compared to those without endometriosis. This study aimed to evaluate preoperative serum AMH levels among women with and without incident endometriosis and to assess whether levels differ by surgical staging and typology. The ENDO (Endometriosis: Natural History, Diagnosis, and Outcomes) study was conducted between 2007 and 2009. The ENDO study consisted of an operative and population cohort (n=600). Only those in the ENDO operative cohort from the Utah site were used for this analysis, and included women aged 18 to 44 years who were scheduled for gynecologic surgery, irrespective of clinical indication (n=476). AMH levels were measured from stored serum collected before surgery using a quantitative enzyme-linked immunosorbent assay. After excluding participants with missing outcome data (n=51), unilateral oophorectomy (n=8), or those within the population cohort (n=69), 348 participants remained for the analysis. Surgically confirmed endometriosis diagnosis, staging (American Society for Reproductive Medicine I-IV), and typology (superficial, deep, ovarian) were ascertained by the operative report. Outliers for AMH (>14.0 ng/mL) were excluded from the analyses and AMH values were log-transformed. Multivariable linear regression models adjusted for age (squared and continuous), body mass index, serum cotinine levels, and exogenous hormonal contraceptive use were conducted. Percentage differences in AMH were calculated as (exp[β]-1)×100, and 95% confidence intervals were reported. Compared with no endometriosis, incident endometriosis diagnosis was associated with lower AMH levels (-19.8%; 95% confidence interval, -37.0 to 1.0); however, this association was not statistically significant. Stage III to IV disease was associated with 40.1% lower AMH levels (95% confidence interval, -58.9 to -12.7). Ovarian endometriomas were most strongly associated with lower AMH levels (-54.3%; 95% confidence interval, -69.4 to -31.8), with a more pronounced association among those with infertility (-72.6%; 95% confidence interval, -85.4 to -48.5). Deep (-24.1%; 95% confidence interval, -48.2 to 11.0) and superficial (-15.5%; 95% confidence interval, -34.6 to 9.3) endometriosis also showed a trend toward lower AMH levels, but these findings were not statistically significant. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis was associated with 26.8% lower AMH levels (95% confidence interval, -44.6 to -3.4). Stage III to IV disease was associated with 47.8% lower AMH levels (95% confidence interval, -65.8 to -23.2), and all subtypes of endometriosis were statistically significantly associated with lower levels of AMH compared with a postoperative diagnosis of a normal pelvis (ovarian: -60.8%; 95% confidence interval, -74.4 to -39.9; deep: -34.3%; 95% confidence interval, -56.2 to -1.4; superficial: -24.8%; 95% confidence interval, -43.9 to -0.8). Ovarian and moderate to severe (stage III-IV) endometriosis were associated with markedly lower AMH levels compared with no endometriosis. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis and moderate to severe stages (stage III-IV) were associated with statistically significantly lower AMH levels. Additionally, typology (deep, ovarian, or superficial) was associated with statistically significantly lower AMH levels. However, this association was likely driven by the presence of ovarian endometriomas across all subtypes. These findings are consistent with previous studies and demonstrate that endometriosis lesions themselves, independent of surgical intervention, influence AMH levels.
Hsu JZ et al., 2025 · Eur J Obstet Gynecol Reprod Biol
Endometriosis is a chronic gynaecological condition affecting reproductive-aged women. It has been associated with infertility and potential risks for adverse pregnancy outcomes, although population-level evidence remains limited. This retrospective cohort study, including 147,950 pregnant women aged 20-45 years, used nationwide population-based data to compare the outcomes between women with (n = 11,400) and without (n = 136,550) endometriosis between 2000 and 2021. Baseline characteristics, comorbidities and pregnancy outcomes were compared between the groups. Multivariable regression analyses were performed to calculate adjusted relative risks (aRR) and 95 % confidence intervals (CI) for various pregnancy outcomes, and subgroup analyses were conducted by maternal age and infertility status. Among 147,950 pregnancies, women with endometriosis [mean ± standard deviation (SD) age 32.38 ± 4.51 years] had higher socio-economic status, more comorbidities, and more surgical history compared with women without endometriosis (mean ± SD age 30.06 ± 4.96 years). Women with endometriosis had increased risk of miscarriage (aRR 1.13, 95 % CI 1.03-1.24), preterm birth (aRR 1.31, 95 % CI 1.26-1.37), premature rupture of membranes (aRR 1.11, 95 % CI 1.06-1.16), placenta previa (aRR 1.63, 95 % CI 1.45-1.84), urinary tract infection (aRR 1.44, 95 % CI 1.31-1.59), and caesarean section (aRR 1.13, 95 % CI 1.11-1.16). Subgroup analysis revealed that risk of miscarriage was only higher in women aged 35-45 years and women without infertility. Risks of preterm birth, placenta previa and caesarean section were elevated across all subgroups, suggesting that endometriosis contributes independently to adverse pregnancy outcomes. Endometriosis is an independent risk factor for several pregnancy complications, supporting the need for tailored prenatal care and closer monitoring of affected women to improve maternal outcomes.
Russo LM et al., 2025 · Ecotoxicol Environ Saf · Free full text on PubMed Central
Prior studies have observed impacts of air pollution on semen quality, but timing of exposure during developmental windows of spermatogenesis and impacts of low-to-moderate air pollution is less well understood. We examined the relation between air pollution and semen quality in the Folic Acid and Zinc Supplementation Trial (2013-2018), which enrolled male partners of couples seeking infertility treatment in the Salt Lake City, Utah region (n = 2015). Semen quality parameters were assessed at baseline, 2-, 4-, and 6-months follow-up. Measures of daily air pollutants at each participant's residence were abstracted from Community Multiscale Air Quality models (fine particulate matter: PM2.5, sulfur dioxide, nitrogen dioxide, and ozone: O3), linked to participants' residential addresses, and averaged across the 74-day spermatogenesis window prior to the sample collection date for each study visit, and across four developmental windows of spermatogenesis (mitosis, meiosis I-II, spermiogenesis, and spermiation). Generalized linear mixed models considered four repeated semen sample measures per participant and adjusted for co-pollutants, age, season, and income. In multi-pollutant models, O3 during early-to-mid spermatogenesis (meiosis I+II and spermiogenesis) was related to lower percent normal morphology (% difference -6.73, 95 % CI -9.82, -3.54 and % difference -3.83, 95 % CI -7.51, 0.00, respectively). Additionally, PM2.5 and O3 during late spermatogenesis (spermiation) were associated with lower count and concentration, and PM2.5 with lower progressive motility. These findings suggest that exposure to low-to-moderate levels of air pollution may negatively impact semen quality and indicate that exposure to O3 during meiosis and spermiogenesis may particularly affect normal sperm morphological development.
Buck Louis GM et al., 2013 · Fertil Steril · Free full text on PubMed Central
To assess in utero exposures and the odds of an endometriosis diagnosis. Matched cohort design. Fourteen participating clinical centers in geographically defined areas in Utah and California. PATIENT(S): Operative cohort comprised 473 women undergoing laparoscopy/laparotomy, and an ageand residence-matched population cohort comprising 127 women undergoing pelvic magnetic resonance imaging (MRI), 2007-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women completed standardized interviews before surgery or MRI regarding in utero exposures: mothers' lifestyle during the index pregnancy, and the index woman's gestation and birth size. Endometriosis was defined as visually confirmed disease in the operative cohort, and MRI visualized disease in the population cohort. The odds of an endometriosis diagnosis and corresponding 95% confidence intervals (CI) were estimated for each exposure by cohort using logistic regression and adjusting for current smoking, age at menarche, body mass index, and study site. RESULT(S): Endometriosis was diagnosed in 41% and 11% of women in the operative and population cohorts, respectively. In the primary analysis, adjust odds ratios (AORs) were elevated for maternal vitamin usage (1.27; 95% CI, 0.85-1.91), maternal cigarette smoking (1.16; 95% CI = 0.61-2.24), and low birth weight (1.1; 95% CI, 0.92-1.32). Reduced odds were observed for maternal usage of caffeine (0.99; 95% CI, 0.64-1.54), alcohol (0.82; 95% CI, 0.35-1.94), paternal cigarette smoking (0.72; 95% CI, 0.43-1.19), and preterm delivery (0.98; 95% CI, 0.47-2.03). Sensitivity analyses mostly upheld the primary results except for a decreased AOR for preterm birth (0.41; 95% CI, 0.18-0.94) when restricting to visualized and histologically confirmed endometriosis in the operative cohort. CONCLUSION(S): In utero exposures were not statistically significantly associated with the odds of an endometriosis diagnosis in either cohort.
Buck Louis GM et al., 2012 · Environ Health Perspect · Free full text on PubMed Central
An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies. We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort. Using a matched cohort design, we assembled an operative cohort of women 18-44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids. Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72). Using a matched cohort design, we found that cohort-specific and biological-medium-specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.
Hemmert R et al., 2018 · Paediatr Perinat Epidemiol · Free full text on PubMed Central
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 18-44 years, 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 ≥10 ng/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.
Pollack AZ et al., 2013 · Reprod Toxicol · Free full text on PubMed Central
There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.
