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Introduction: Prior studies have investigated the diagnostic potential of microRNA (miRNA) expression profiles for endometriosis. However, the vast majority of previous studies have only included adult women. Therefore, we sought to investigate differential expression of miRNAs among adolescents and young adults with endometriosis. Methods: The Women's Health Study: from Adolescence to Adulthood (A2A) is an ongoing WERF EPHect compliant longitudinal cohort. Our analysis included 64 patients with surgically-confirmed endometriosis (96% rASRM stage I/II) and 118 females never diagnosed with endometriosis frequency matched on age (median = 21 years) and hormone use at blood draw. MicroRNA measurement was separated into discovery (10 cases and 10 controls) and internal replication (54 cases and 108 controls) phases. The levels of 754 plasma miRNAs were assayed in the discovery phase using PCR with rigorous internal control measures, with the relative expression of miRNA among cases vs. controls calculated using the 2-ΔΔCt method. miRNAs that were significant in univariate analyses stratified by hormone use were included in the internal replication phase. The internal replication phase was split 2:1 into a training and testing set and utilized FirePlex miRNA assay to assess 63 miRNAs in neural network analyses. The testing set of the validation phase was utilized to calculate the area under the curve (AUC) of the best fit models from the training set including hormone use as a covariate. Results: In the discovery phase, 49 miRNAs were differentially expressed between endometriosis cases and controls. The associations of the 49 miRNAs differed by hormone use at the time of blood draw. Neural network analysis in the testing set of the internal replication phase determined a final model comprising 5 miRNAs (miR-542-3p, let-7b-3p, miR-548i, miR-769-5p, miR-30c-1-3p), yielding AUC = 0.77 (95% CI: 0.67--0.87, p < 0.001). Sensitivity in the testing dataset improved (83.3% vs. 72.2%) while the specificity decreased (58.3% vs. 72.2%) compared to the training set. Conclusion: The results suggest that miR-542-3p, let-7b-3p, miR-548i, miR-769- 5p, miR-30c-1-3p may be dysregulated among adolescent and young adults with endometriosis. Hormone use was a significant modifier of miRNA dysregulation and should be considered rigorously in miRNA diagnostic studies. [ABSTRACT FROM AUTHOR]

Introduction: Over four million women in the US alone have been diagnosed with endometriosis. For those living with this disease, surgery and hormonal treatment reduce associated pelvic pain in some, while others continue to experience life impacting pain. Therefore, identification of accessible and cost-effective methods of pain reduction to compliment current treatment is urgently needed. Our objective was to quantify the prevalence of complementary and alternative methods used to manage acyclic pelvic pain and their reported benefit among women of different age groups living with endometriosis. Methods: We used baseline questionnaire data from laparoscopically-confirmed endometriosis cases who completed a WERF EPHect compliant questionnaire in the longitudinal cohort of The Women's Health Study: From Adolescence to Adulthood (A2A). Participants with acyclic pelvic pain were asked to indicate specific methods or activities that either helped or worsened their pelvic/lower abdominal pain. Differences among age groups [adolescent (<18 years), young adult (18-25 years), and adult (>25 years)] were assessed using Fisher's exact test. Results: Of the 357 participants included in analysis, sleep for coping was reported more frequently among adolescents (n = 59, 57.3%) compared to young adults (n = 40, 44.0%) and adults (n=19, 31.1%; p = 0.004). Adolescents also reported more frequent use of music (n = 29, 21.2%) than young adults (n = 10, 7.0%) and adults (n = 7, 9.1%; p = 0.001). Exercise worsened pain most commonly among adolescents (n = 82, 59.9%), followed by younger adults (n = 67, 46.9%), and adults (n=27, 35.1%; p=0.002). Discussion: Our analysis of participants in the A2A cohort showed that the prevalence of complementary and alternative methods used for coping with endometriosis-associated acyclic pelvic pain varied by age group. Future studies should aim to provide information that will further inform decisions in making care plans for managing endometriosis-associated pain that is effective, accessible, and tailored to the preferences of the patient. [ABSTRACT FROM AUTHOR]

Background: Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures. The literature regarding cardiovascular disease (CVD) risk after these surgeries has focused on oophorectomy with limited research on hysterectomy or tubal ligation. Materials and Methods: Participants in the Nurses' Health Study II (n = 116,429) were followed from 1989 to 2017. Self-reported gynecologic surgery was categorized as follows: no surgery, hysterectomy alone, hysterectomy with unilateral oophorectomy, and hysterectomy with bilateral oophorectomy. We separately investigated tubal ligation alone. The primary outcome was CVD based on medical-record confirmed fatal and nonfatal myocardial infarction, fatal coronary heart disease, or fatal and nonfatal stroke. Our secondary outcome expanded CVD to include coronary revascularization (coronary artery bypass graft surgery, angioplasty, stent placement). Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) and were adjusted a priori for confounding factors. We investigated differences by age at surgery (≤50, >50) and menopausal hormone therapy usage. Results: At baseline, participants were on average, 34 years old. During 2,899,787 person-years, we observed 1,864 cases of CVD. Hysterectomy in combination with any oophorectomy was associated with a greater risk of CVD in multivariable-adjusted models (HR hysterectomy with unilateral oophorectomy:1.40 [95% CI: 1.08–1.82]; HR hysterectomy with bilateral oophorectomy:1.27 [1.07–1.51]). Hysterectomy alone, hysterectomy with oophorectomy, and tubal ligation were also associated with an increased risk of combined CVD and coronary revascularization (HR hysterectomy alone: 1.19 [95% CI: 1.02–1.39]; HR hysterectomy with unilateral oophorectomy: 1.29 [1.01–1.64]; HR hysterectomy with bilateral oophorectomy: 1.22 [1.04–1.43]; HR tubal ligation: 1.16 [1.06–1.28]). The association between hysterectomy/oophorectomy and CVD and coronary revascularization risk varied by age at gynecologic surgery, with the strongest association among women who had surgery before age 50 years. Conclusion: Our findings suggest that hysterectomy, alone or in combination with oophorectomy, as well as tubal ligation, may be associated with an increased risk of CVD and coronary revascularization. These findings extend previous research finding that oophorectomy is associated with CVD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Question: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization?Summary Answer: Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization.What Is Known Already: Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias.Study Design, Size, Duration: Massachusetts deliveries among women ≥18 years old during 2013-2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD).Participants/materials, Setting, Methods: PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories (<30, ≥30, <25 and ≥25 kg/m2) and between non-infertile deliveries and deliveries that used ART or had a history of subfertility (defined by birth certificates, SART CORS records, APCD or hospital records).Main Results and the Role Of Chance: Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06-1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09-1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI <30 kg/m2.Limitations, Reasons For Caution: PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured.Wider Implications Of the Findings: In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients' PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes.Study Funding/competing Interest(s): This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women's Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: The etiology of endometriosis is not well understood. Limited evidence suggests that dietary factors influence risk, but prospective data related to carbohydrate, fiber, and gluten consumption are scarce. Despite this, recommendations concerning fiber, gluten intake, and endometriosis are pervasive in the lay literature.Objectives: We aimed to investigate the associations of carbohydrate quality [glycemic index (GI) and glycemic load (GL)], fiber intake (total, legume, vegetable, cruciferous vegetable, fruit, cereal), and gluten intake with incident laparoscopically confirmed endometriosis.Methods: This was a prospective cohort study using data collected from 81,961 premenopausal women in the Nurses' Health Study II (mean age = 36 y in 1991). Diet was assessed with a validated FFQ every 4 y. Cox proportional hazards models were used to calculate rate ratios (RRs) and 95% CIs.Results: A total of 3810 incident cases of laparoscopically confirmed endometriosis were reported over 24 y of follow-up. Women in the highest quintile of GI had 12% (95% CI: 1.01, 1.23; Ptrend = 0.03) higher risk of endometriosis diagnosis than those in the lowest quintile. Total vegetable and cruciferous vegetable fiber intakes were also associated with higher risk (highest compared with lowest quintile RR: 1.13; 95% CI: 1.02, 1.24; Ptrend = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; Ptrend = 0.02, respectively). Higher intake of fruit fiber was associated with lower risk of endometriosis but the association was not significant after adjusting for the Alternative Healthy Eating Index. Gluten intake was also associated with lower risk (highest compared with lowest quintile RR: 0.91; 95% CI: 0.80, 1.02; Ptrend = 0.01), but these results were not consistent in direction nor statistical significance across sensitivity analyses. No association was observed for GL or total, legume, or cereal fiber intake.Conclusions: Our findings suggest that carbohydrate quality and specific types of fiber-total vegetable and cruciferous vegetable fiber-are associated with endometriosis diagnosis in premenopausal women. These results also indicate it is unlikely that gluten intake is a strong factor in the etiology or symptomatology of endometriosis. [ABSTRACT FROM AUTHOR]

Study Question: What are the systemic molecular profiles of endometriosis diagnosed in adolescents and young adults?Summary Answer: Significant enrichment and increased activation of proteins related to angiogenesis and cell migration pathways were observed in endometriosis cases compared to controls (P-value < 2.4 × 10-8).What Is Known Already: Little is known about the pathophysiology of adolescent endometriosis despite the fact that over 50% of adults with endometriosis report onset of severe pelvic pain during adolescence.Study Design, Size, Duration: A cross-sectional analysis using data on 142 laparoscopically confirmed endometriosis cases and 74 controls from the observational longitudinal cohort of Women's Health Study: From Adolescence to Adulthood (A2A).Participants/materials, Setting, Methods: We measured 1305 plasma protein levels using the validated, multiplex aptamer-based proteomics discovery platform, SOMAscan. We calculated odds ratios and 95% CIs using logistic regression adjusting for age, BMI, fasting status and hormone use at blood draw for differentially expressed proteins (P < 0.05). Ingenuity Pathway Analysis and STRING analysis were performed to identify biological pathways and protein interactions. We also examined proteins and pathways associated with superficial peritoneal lesion colors (i.e. red, vascularized, white, blue/black, brown).Main Results and the Role Of Chance: Average age at blood draw was 18 years for endometriosis cases and 22 years for controls. We identified 63 proteins associated with endometriosis with type-I error set at 0.05, and absolute fold change >1.2, revealing significant enrichment of dysregulated proteins in biological pathways associated with endometriosis. Increased activation of pathways related to angiogenesis and cell migration was observed in plasma from endometriosis cases compared to controls (P-value < 2.4 × 10-8). Furthermore, when we examined proteins and pathways associated with lesion colors, vascularized lesions were associated with upregulation of pathways related to immune cell migration/activation and inflammation, whereas white, blue/black and brown lesions were associated with downregulation of these pathways.Limitations, Reasons For Caution: Validation of our results in independent datasets and mechanistic studies are warranted to further our understanding of the pathophysiological characteristics of this common but understudied patient population.Wider Implications Of the Findings: To our knowledge, this was the first study to comprehensively examine circulating proteins in predominantly adolescents and young adult women with and without endometriosis. Results from this study provide novel biological insight that will build toward further research to elucidate endometriosis pathophysiology during the earlier course of the disease trajectory.Study Funding/competing Interest(s): This study was supported by the Department of Defense (W81XWH1910318) and the 2017 Boston Center for Endometriosis Trainee Award. Financial support for establishment of and data collection within the A2A cohort were provided by the J. Willard and Alice S. Marriott Foundation. N.S., A.F.V., S.A.M., K.L.T. have received funding from Marriott Family Foundation. S.A.M. and K.L.T. are supported by NICHD (R01 HD94842). S.A.M. serves as an advisory board member for AbbVie and Roche; neither are related to this study. The authors report no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?Summary Answer: Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.What Is Known Already: Long and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear.Study Design, Size, Duration: Prospective cohort study. Prospective follow-up of 78 943 women participating in the Nurses' Health Study II between 1989 and 2015.Participants/materials, Setting, Methods: We followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14-17, 18-22 and 29-46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence.Main Results and the Role Of Chance: We documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29-46 years had an 11% (95% CI: 2-21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9-39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09-1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14-17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02-1.81).Limitations, Reasons For Caution: Our study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White.Wider Implications Of the Findings: Women with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood.Study Funding/competing Interest: This work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Is recreational and residential sun exposure associated with risk of endometriosis?Summary Answer: Tanning bed use in early adulthood, sunscreen use and history of sunburns were associated with a greater risk of endometriosis; however, higher residential UV exposure was associated with a lower endometriosis risk.What Is Known Already: Previous research has reported an association between endometriosis and skin cancer, with evidence of shared risk factors between the two diseases. We investigated the potential associations between ultraviolet radiation and endometriosis risk.Study Design, Size, Duration: The Nurses' Health Study II is a prospective cohort of 116 429 female US nurses aged 25-42 years at enrolment in 1989. Participants completed self-administered biennial questionnaires through June 2015.Participants/materials, Settings, Methods: We investigated self-reported measures of recreational sun-exposure and geocoded residential UV exposure in childhood and adulthood in relation to risk of laparoscopically confirmed endometriosis among premenopausal white women. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs.Main Results and the Role Of Chance: During follow-up, 4791 incident cases of laparoscopically confirmed endometriosis were reported among 1 252  248 person-years. Tanning bed use during high school/college (≥6 times per year vs. never use: HR = 1.19, 95% CI = 1.01-1.40; Ptrend = 0.04) and at ages 25-35 (HR = 1.24, 95% CI = 1.12-1.39; Ptrend ≤ 0.0001), number of sunburns during adolescence (Ptrend = 0.03) and percentage of time using sunscreen in adulthood (Ptrend = 0.002) were positively associated with risk of endometriosis. In contrast, residential UV level at birth (highest vs. lowest quintile: HR = 0.81, 95% CI = 0.72-0.92; Ptrend = 0.0001), at age 15 (HR = 0.79, 95% CI = 0.70-0.88; Ptrend ≤ 0.0001) and at age 30 (HR = 0.90, 95% CI = 0.82-0.99; Ptrend = 0.21) were associated with a decreased risk of endometriosis.Limitations, Reasons For Caution: Self-reported endometriosis diagnosis may be prone to misclassification; however, we restricted our definition to laparoscopically confirmed endometriosis, which has been shown to have high validity compared to medical records.Wider Implications Of the Findings: Our results suggest that tanning bed use in early adulthood increases endometriosis risk, potentially through a harmful effect of ultraviolet A wavelengths, and that residential UV exposure reduces risk, possibly via optimal vitamin D synthesis. These findings should be investigated further to enhance our understanding of endometriosis aetiology.Study Funding/competing Interest(s): This project was supported by NICHD grants HD48544 and HD52473, HD57210, NIH grant CA50385, CA176726. M.K. was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) and is grateful to the Philippe Foundation and the Bettencourt-Schueller Foundation for their financial support. H.R.H. is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). The authors have nothing to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

A mediator is a factor that occurs after the exposure of interest, precedes the outcome of interest (i.e. between the exposure and the outcome) and is associated with both the exposure and the outcome of interest (i.e. is on the pathway between exposure and outcome). Mediation analyses can be valuable in many reproductive health contexts, as mediation analysis can help researchers to better identify, quantify and understand the underlying pathways of the association they are studying. The purpose of this commentary is to introduce the concept of mediation and provide examples that solidify understanding of mediation for valid discovery and interpretation in the field of reproductive medicine. [ABSTRACT FROM AUTHOR]

Purpose: Menstrual cycle characteristics are markers of endocrine milieu. However, associations between age at menarche and adulthood sex steroid hormone levels have been inconsistent, and data on menstrual characteristics and non-sex steroid hormones are sparse.Methods: We assessed the relations of menstrual characteristics with premenopausal plasma sex steroid hormones, sex hormone binding globulin (SHBG), prolactin, and growth factors among 2,745 premenopausal women (age 32-52) from the Nurses' Health Study II. Geometric means and tests for trend were calculated using multivariable general linear models.Results: Early age at menarche was associated with higher premenopausal early-follicular free estradiol (percent difference < 12 vs. > 13 years = 11%), early-follicular estrone (7%), luteal estrone (7%), and free testosterone (8%) (all p trend < 0.05). Short menstrual cycle length at age 18-22 was associated with higher early-follicular total (< 26 vs. > 39 days = 18%) and free estradiol (16%), early-follicular estrone (9%), SHBG (7%), lower luteal free estradiol (- 14%), total (- 6%), and free testosterone (- 15%) (all p trend < 0.05). Short adult menstrual length was associated with higher early-follicular total estradiol (< 26 vs. > 31 days = 14%), SHBG (10%), lower luteal estrone (- 8%), progesterone (- 9%), total (- 11%) and free testosterone (- 25%), and androstenedione (- 14%) (all p trend < 0.05). Irregularity of menses at 18-22 was associated with lower early-follicular total (irregular vs. very regular = - 14%) and free estradiol (- 14%), and early-follicular estrone (- 8%) (All p trend < 0.05). Irregularity of adult menstrual cycle was associated with lower luteal total estradiol (irregular vs. very regular = - 8%), SHBG (- 3%), higher total (8%), and free testosterone (11%) (all p trend < 0.05).Conclusions: Early-life and adulthood menstrual characteristics are moderately associated with mid-to-late reproductive year's hormone concentrations. These relations of menstrual characteristics with endogenous hormone levels could partially account for associations between menstrual characteristics and reproductive cancers or other chronic diseases. [ABSTRACT FROM AUTHOR]

Purpose: Endometriosis has been associated with an increased risk of skin melanoma. However, associations with other skin cancer types and how they compare with melanoma are unclear. Our objective was to prospectively investigate the relationships between endometriosis and risk of non-melanoma and melanoma skin cancers.Methods: E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2-3 years through self-report, with skin cancer cases confirmed through pathology reports. Hazard Ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox regression models.Results: Between 1990 and 2008, 535 melanoma, 247 squamous-cell carcinoma (SCC), and 1,712 basal-cell carcinoma (BCC) cases were ascertained. Endometriosis was associated with an increased overall risk of skin cancer (HR 1.28, 95% CI 1.05-1.55). When considering skin cancer type, endometriosis was associated with melanoma risk (HR 1.64, 95% CI 1.15-2.35), but not with SCC (HR 1.21, 95% CI 0.62-2.36) or BCC (HR 1.16, 95% CI 0.91-1.48) (non-melanoma skin cancers combined: HR 1.17, 95% CI 0.93-1.46), although no heterogeneity was detected across skin cancer types (Phomogeneity = 0.13).Conclusion: These data support an association between a personal history of endometriosis and the risk of skin cancer and suggest that the association is strongest for melanoma. [ABSTRACT FROM AUTHOR]

Purpose: The influence of reproductive factors on colorectal cancer, including oral contraceptive (OC) use, has been examined, but less research is available on OC use and adenomas.Methods: Participants of the Nurses' Health Study who had a lower bowel endoscopy between 1986 (when endoscopies were first assessed) and 2008 were included in this study. Multivariable logistic regression models for clustered data were used to estimate odds ratios and 95 % confidence intervals [OR (95 % CIs)].Results: Among 73,058 participants, 51 % (n = 37,382) reported ever using OCs. Ever OC use was associated with a slight increase in non-advanced adenomas [OR 1.11, 95 % CI (1.02, 1.21)] but not with any other endpoints. Duration of OC use was not associated with adenomas, but longer times since last OC use were associated with increased odds of adenomas [e.g., compared to never use, 15+ years since last use: OR 1.17 (1.07, 1.27)]. Shorter times since last OC use were inversely associated [e.g., ≤4 years since last use: OR 0.74 (0.65, 0.84)].Conclusions: We observed a modest borderline increase in risk of colorectal adenomas with any prior OC use. Additionally, more recent OC use may decrease risk, while exposure in the distant past may modestly increase risk of adenomas. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between physical and sexual abuse occurring in childhood or adolescence and risk of laparoscopically-confirmed endometriosis?Summary Answer: Early life sexual and physical abuse was associated with an increased risk of endometriosis.What Is Known Already: Previous studies have reported that physical and sexual abuse are associated with chronic pelvic pain (CPP). However, only one study has examined the association between childhood physical abuse and laparoscopically-confirmed endometriosis, and did not observe an association with endometriosis risk.Study Design, Size, Duration: Prospective cohort study using data collected from 60 595 premenopausal women from 1989 to 2013 as part of the Nurses' Health Study II cohort.Participants/materials, Setting, Methods: Participants completed an exposure to violence victimization questionnaire in 2001. Cases were restricted to laparoscopically-confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% confidence intervals (CI).Main Results and the Role Of Chance: Three thousand three hundred and ninety-four cases of laparoscopically-confirmed endometriosis were diagnosed during 24 years of follow-up. Compared to those reporting no physical or sexual abuse, the risk of endometriosis was greater among those who experienced severe physical abuse (RR = 1.20; 95% CI = 1.06, 1.37) or severe sexual abuse (RR = 1.49; 95% CI = 1.24, 1.79). There was a 79% increased risk of laparoscopically-confirmed endometriosis for women reporting severe-chronic abuse of multiple types (95% CI = 1.44, 2.22). The associations between abuse and endometriosis were stronger among women presenting without infertility, a group that was more likely to have been symptomatic with respect to pain.Limitations, Reasons For Caution: The violence exposure was recalled by the study participants and thus is subject to misclassification as well as recall bias for the cases who were diagnosed prior to 2001. However, our results were similar in a sensitivity analysis including only endometriosis cases incident after their violence history report. In addition, residual or unmeasured confounding is a possibility; however, we were able to adjust for a variety of potential early life confounders. Finally, selection bias is also a possibility if those who chose to return the violence questionnaire did so based jointly on abuse history and endometriosis risk.Wider Implications Of the Findings: Early life sexual and physical abuse was associated with an increased risk of endometriosis. Severity, chronicity and accumulation of types of abuse were associated with greater risk. Understanding the mechanisms underlying these relations may better define the biologic impacts of abuse and the related pathophysiology of endometriosis.Study Funding/competing Interest(s): This work was supported by National Institute of Child Health and Human Development [Grant numbers HD48544, HD52473, HD57210 and CA50385] and the Atlanta Clinical and Translational Science Institute [Grant number ULRR025008]. The Nurses' Health Study II is supported by the National Institutes of Health grant UM1 CA176726 from the National Cancer Institute. H.R.H. is supported by the National Cancer Institute, National Institutes of Health [Grant number K22 CA193860]. Authors report no conflict of interest. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate associations between maternal history of rotating night shift nursing work before pregnancy and number of night shifts worked during pregnancy with offspring weight outcomes from early life through adolescence.Methods: More than 4,000 children, enrolled in the second phase of the Growing Up Today Study between 2004 and 2013, and their mothers participating in the Nurses' Health Study II were included in our analyses.Results: Children of women with and without a history of rotating night shift work before pregnancy were similar in birth weight and body size at age 5. However, for mothers with night shift work before pregnancy, their children had a modestly elevated risk of having overweight or obesity (relative risk = 1.11; 95% CI: 1.02-1.21), which was stronger for persistently having overweight or obesity during adolescence and early adulthood. Longer duration of rotating night shift work was not associated with any of these weight outcomes. Weight outcomes of children of women with versus without night shift work during pregnancy were similar, regardless of frequency of night shifts worked during pregnancy (all P > 0.09).Conclusions: Overall, nurses' night shift work before or during pregnancy did not affect offspring weight outcomes. Future larger studies should explore these associations in more detail. [ABSTRACT FROM AUTHOR]

Background: Animal data suggest sexually dimorphic programming of obesity in response to altered intrauterine environment, but the longitudinal impact of gestational diabetes mellitus (GDM) on sex-specific risk of offspring obesity in humans is unclear.Methods: We conducted a prospective analysis of 15 009 US individuals (7946 female and 7063 male) from the Growing-Up Today Study, who were followed from 1996 (ages 9-14 years) through 2010. Height and weight from validated questionnaires were used to derive body mass index (BMI) at different ages. Obesity during childhood (< 18 years) and adulthood (≥ 18 years) were defined using the International Obesity Task Force and the World Health Organization criteria. GDM exposure was identified through self-reported questionnaires from mothers. Relative risks were estimated using multivariable log-binomial regression models with generalized estimating equations accounting for clustering within the same family.Results: Male offspring born from pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and had increased risk of obesity; the adjusted relative risk [RR, 95% confidence interval (CI)] was 1.47 (1.11-1.95) for all age groups, 1.59 (1.05-2.41) for late childhood, 1.48 (1.06-2.06) for adolescence and 1.39 (1.00-1.94) for early adulthood. No significant association between obesity and maternal GDM was observed among female participants (RR = 0.97, 95% CI: 0.71-1.33).Conclusions: The association of GDM with offspring obesity from late childhood through early adulthood may differ by sex; a significant association was observed among male but not female offspring. [ABSTRACT FROM AUTHOR]

Study question: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis?Summary answer: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways.What is known already: Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis.Study design size, duration: Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies.Participants/materials, setting, methods: The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software.Main results and the role of chance: The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10-4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10-5, FDR-P = 3.0 × 10-3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10-4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10-4, FDR-P = 5.0 × 10-4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology-Core matrisome (P = 1.4 × 10-3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10-3, FDR-P = 7.1 × 10-3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10-12), Apoptosis signaling pathway (P = 9.7 × 10-9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10-6); however, these pathways did not feature in the results based on GWAS data.Large scale data: Not applicable.Limitations, reasons for caution: The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry.Wider implications of the findings: The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis.Study funding/competing interest(s): The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest. [ABSTRACT FROM AUTHOR]

Objectives: The aetiologies of endometriosis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are all characterised by immune dysfunction. SLE and RA occur more often in women, and reproductive and hormonal factors have been shown to be related to increased risk. However, only one previous study has evaluated the temporal association between endometriosis and SLE or RA. We sought to investigate the association between laparoscopically confirmed endometriosis and subsequently diagnosed SLE and RA.Methods: We analysed data from the Nurses' Health Study II (n=114 453 women) over a 22-year follow-up period. Multivariable, time-varying Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between laparoscopically confirmed endometriosis and confirmed incident SLE or RA.Results: From 1989 to 2011, 103 incident cases of SLE and 390 cases of RA were confirmed. Laparoscopically confirmed endometriosis was significantly associated with subsequent SLE diagnosis (HR=2.03; CI 1.17 to 3.51) and RA diagnosis (HR=1.41; CI 1.05 to 1.89). These associations were robust to adjustment for SLE or RA risk factors and for potential confounders; however, adjustment for hysterectomy and oophorectomy attenuated both relations such that they were no longer significant. No significant differences by infertility status or age (<45 years) were observed.Conclusions: Our findings suggest an association between endometriosis and risk of SLE and RA. It remains to be understood whether and how endometriosis itself, or hysterectomy or other factors associated with endometriosis, is related to risk of SLE or RA. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women's risk for coronary heart disease (CHD).Methods and Results: We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses' Health Study II (1989-2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98), angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these CHD end points combined (1.62; 1.39-1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02-4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35-2.02; 50< age ≤55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis.Conclusions: In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes. OBJECTIVES: We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth. METHODS: Male--female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males' specific gravity--adjusted urinary phenol concentrations measured before females' cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple. RESULTS: Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82). CONCLUSIONS: TO our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population. [ABSTRACT FROM AUTHOR]

Background: Endometriosis and uterine fibroids are common gynecologic conditions associated with a greater risk for infertility. Previous research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially because of increased utilization of fertility treatments.Objective: Our objective was to investigate whether women with a history of endometriosis or fibroids had a greater risk for adverse pregnancy outcomes and whether this risk varied by infertility history and fertility treatment utilization.Study Design: Deliveries (2013-2017) recorded in Massachusetts' vital records were linked to assisted reproductive technology data, hospital stays, and all-payer claims database. We identified endometriosis and fibroids diagnoses via the all-payer claims database before index delivery. Adjusted relative risks for pregnancy complications were modeled using generalized estimating equations with a log link and Poisson distribution. The influence of subfertility or infertility and assisted reproductive technology was also investigated.Results: Among 91,825 deliveries, 1560 women had endometriosis and 4212 had fibroids. Approximately 30% of women with endometriosis and 26% of women with fibroids experienced subfertility or infertility without utilizing assisted reproductive technology, and 34% of women with endometriosis and 21% of women with fibroids utilized assisted reproductive technology for the index delivery. Women with a history of endometriosis or fibroids were at a greater risk for pregnancy-induced hypertension, preeclampsia, or eclampsia (endometriosis relative risk, 1.17; fibroids relative risk, 1.08), placental abnormalities (endometriosis relative risk, 1.65; fibroids relative risk, 1.38), and cesarean delivery (endometriosis relative risk, 1.22; fibroids relative risk, 1.17) than women with no history of those conditions. Neonates born to women with a history of endometriosis or fibroids were also at a greater risk for preterm birth (endometriosis relative risk, 1.24; fibroids relative risk, 1.17). Associations between fibroids and low birthweight varied by fertility status or assisted reproductive technology (P homogeneity=.01) and were stronger among noninfertile women.Conclusion: Endometriosis or fibroids increased the risk for adverse pregnancy outcomes, possibly warranting differential screening or treatment. [ABSTRACT FROM AUTHOR]

Background: Two previous case-control studies observed associations between specific food groups and risk of miscarriage; however, to our knowledge, no previous studies have investigated dietary patterns and risk of pregnancy loss. Objective: We aimed to assess prepregnancy adherence to the alternate Healthy Eating Index 2010 (aHEI-2010), alternate Mediterranean diet (aMED), and Fertility Diet (FD) and risk of pregnancy loss. Design: Our prospective cohort study included 15,950 pregnancies reported by 11,072 women in the Nurses' Health Study II between 1992 and 2009. Diet was assessed every 4 y starting in 1991 by using a validated food-frequency questionnaire. Prepregnancy dietary pattern scores were computed as the sum of a woman's score on each pattern's predefined components. Multivariable log-binomial regression models with generalized estimating equations were used to estimate RRs and 95% CIs. Results: Incident spontaneous abortions and stillbirths were reported in 2756 (17.3%) and 120 (0.8%) pregnancies, respectively. None of the 3 dietary patterns were associated with risk of pregnancy loss. In the multivariable model, RR of pregnancy loss for a 1-SD increase in score was 1.02 (95% CI: 0.98, 1.05) for the aMED pattern, 1.01 (95% CI: 0.98, 1.05) for the aHEI-2010 pattern, and 0.98 (95% CI: 0.95, 1.01) for the FD pattern. Results were consistent when pregnancy loss was classified as either a spontaneous abortion (loss at <20 wk) or a stillbirth (loss at ≥20 wk). Conclusion: Prepregnancy adherence to several dietary patterns was not associated with risk of pregnancy loss. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that violence victimization is prevalent among women with premenstrual syndrome (PMS). However, it is unclear whether early life abuse contributes directly to PMS or whether associations are explained by the high prevalence of PMS risk factors including smoking and obesity among women reporting childhood abuse. Methods: We have assessed the relation of early life abuse and the incidence of moderate-to-severe PMS in a study nested within the prospective Nurses' Health Study 2. Participants were aged 27-44 years and free from PMS at baseline, including 1,018 cases developing PMS over 14 years and 2,277 comparison women experiencing minimal menstrual symptoms. History of early life emotional, physical, and sexual abuse was self-reported in 2001. Results: After adjustment for obesity, smoking, and other factors, emotional abuse was strongly related to PMS ( pTrend<0.0001); women reporting the highest level of emotional abuse had 2.6 times the risk of PMS as those reporting no emotional abuse (95% confidence interval, 1.7-3.9). Women reporting severe childhood physical abuse had an odds ratio of 2.1 (95% confidence interval, 1.5-2.9; pTrend<0.001) compared with those reporting no physical abuse. Sexual abuse was less strongly associated with risk. Adjustment for childhood social support minimally affected findings. Conclusions: Findings from this large prospective study suggest that early life emotional and physical abuse increase the risk of PMS in the middle-to-late reproductive years. The persistence of associations after control for potential confounders and mediators supports the hypothesis that early life abuse is importantly related to PMS. [ABSTRACT FROM AUTHOR]

Objectives. Reproductive health screenings are a necessary part of quality health care. However, sexual minorities underutilize Papanicolaou (Pap) tests more than heterosexuals do, and the reasons are not known. Our objective was to examine if less hormonal contraceptive use or less positive health beliefs about Pap tests explain sexual orientation disparities in Pap test intention and utilization. Methods. We used multivariable regression with prospective data gathered from 3821 females aged 18 to 25 years in the Growing Up Today Study (GUTS). Results. Among lesbians, less hormonal contraceptive use explained 8.6% of the disparities in Pap test intention and 36.1% of the disparities in Pap test utilization. Less positive health beliefs associated with Pap testing explained 19.1% of the disparities in Pap test intention. Together, less hormonal contraceptive use and less positive health beliefs explained 29.3% of the disparities in Pap test intention and 42.2% of the disparities in Pap test utilization. Conclusions. Hormonal contraceptive use and health beliefs, to a lesser extent, help to explain sexual orientation disparities in intention and receipt of a Pap test, especially among lesbians. [ABSTRACT FROM AUTHOR]

Previous studies evaluating the association of prenatal exposure to diethylstilbestrol (DES), a potent endocrine disruptor, with incidence of uterine leiomyomata (UL) have had conflicting results. We evaluated the association between prenatal DES exposure and incident UL in women in the Nurses' Health Study II from 1989 to 2009. Women were aged 25–42 years at enrollment and had a prenatal exposure window corresponding to DES use. The analytical sample was larger than previous studies and included 102,164 premenopausal women with intact uteri, no prior history of UL or cancer, and prenatal DES exposure. Multivariable-adjusted Cox proportional hazard models were used to estimate the relationship between DES exposure and UL risk. During 1,273,342 person-years of follow-up, there were 11,831 incident cases of UL. Women with prenatal exposure to DES had a higher incidence of UL compared with unexposed women, with an adjusted hazard ratio of 1.12 (95% confidence interval: 0.98, 1.27). Risk was strongest for women exposed to DES in the first trimester, when exposure corresponds to early stages of fetal Müllerian development (adjusted hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). These results suggest that first-trimester DES exposure may be associated with an increased risk of UL, but they must be interpreted with concern for detection and recall biases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Studies of delayed conception and risk of gestational diabetes (GDM) are sparse, although common underlying mechanisms are plausible, including insulin resistance and inflammation. The association between a history of infertility and GDM was assessed prospectively among 40,773 eligible pregnancies in the US Nurses' Health Study II cohort (1989–2001). Biennial questionnaires provided updated information on infertility and several lifestyle and health-related characteristics. Multivariable log-binomial models with generalized estimating equations were used to compute risk ratios and 95% confidence intervals, adjusting for age, prepregnancy body mass index (weight (kg)/height (m)2), and additional potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy history of infertility was reported by 5,497 (20.5%) participants and was significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39, 95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI: 1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P = 0.005). The association of cervical mucus disorder with GDM was of borderline significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27, 95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI: 0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings suggest that infertility, particularly from ovulation disorders and tubal blockage, is associated with an increased GDM risk. Further research is needed to identify mechanisms or common underlying metabolic dysfunction explaining these observations. [ABSTRACT FROM PUBLISHER]

The etiology of endometriosis is poorly understood, and few modifiable risk factors have been identified. Dairy foods and some nutrients can modulate inflammatory and immune factors, which are altered in women with endometriosis. We investigated whether intake of dairy foods, nutrients concentrated in dairy foods, and predicted plasma 25-hydroxyvitamin D (25(OH)D) levels were associated with incident laparoscopically confirmed endometriosis among 70,556 US women in Nurses’ Health Study II. Diet was assessed via food frequency questionnaire. A score for predicted 25(OH)D level was calculated for each participant. During 737,712 person-years of follow-up over a 14-year period (1991–2005), 1,385 cases of incident laparoscopically confirmed endometriosis were reported. Intakes of total and low-fat dairy foods were associated with a lower risk of endometriosis. Women consuming more than 3 servings of total dairy foods per day were 18% less likely to be diagnosed with endometriosis than those reporting 2 servings per day (rate ratio = 0.82, 95% confidence interval: 0.71, 0.95; Ptrend = 0.03). In addition, predicted plasma 25(OH)D level was inversely associated with endometriosis. Women in the highest quintile of predicted vitamin D level had a 24% lower risk of endometriosis than women in the lowest quintile (rate ratio = 0.76, 95% confidence interval: 0.60, 0.97; Ptrend = 0.004). Our findings suggest that greater predicted plasma 25(OH)D levels and higher intake of dairy foods are associated with a decreased risk of endometriosis. [ABSTRACT FROM PUBLISHER]

Background: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. Objective: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). Methods: We used online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval. Results: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). Conclusion: There was a positive linear dose-response association between BPA urinary concentrations and implantation failure. [ABSTRACT FROM AUTHOR]

Purpose. It is well known that chemotherapy regimens may have a negative effect on ovarian reserve, leading to amenorrhea or premature ovarian failure. There are little data regarding the effects of leukemia chemotherapy on ovarian reserve, specifically in women who received the chemotherapy as adults and are having regular menstrual periods. Our primary objective was to determine if premenopausal women with a history of chemotherapy for leukemia, without subsequent stem cell transplantation, have decreased ovarian reserve. Materials and Methods. Wemeasured ovarian reserve in five women who had been treated for acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) and compared them to age-matched control women without a history of chemotherapy. Results. There appeared to be a trend towards lower antimullerian hormone and antral follicle counts and higher follicle-stimulating hormone levels in the leukemia group. Conclusion. Our results indicate that chemotherapy for AML or ALL without stem cell transplantation may compromise ovarian reserve. Although our results should be confirmed by a larger study, oncologists, infertility specialists, and patients should be aware of the potential risks to ovarian function and should be counseled on options for fertility preservation. [ABSTRACT FROM AUTHOR]

Background: Infertility and early pregnancy loss are prevalent as is exposure to secondhand tobacco smoke (STS). Previous research has suggested a relationship between STS exposure and early pregnancy loss, but studies have been limited by small study sizes and/or imprecise methods for exposure estimation. IVF allows for the collection of follicular fluid (FF), the fluid surrounding the pre-ovulatory oocyte, which may be a more biologically relevant sample media than urine or serum in studies of early reproduction.Methods: In a retrospective analysis of a prospective cohort study, we measured cotinine in FF collected during 3270 IVF treatment cycles from 1909 non-smoking women between 1994 and 2003 to examine the relationship between STS exposure and implantation failure.Results: In adjusted models, we found a significant increase in the risk of implantation failure among women exposed to STS compared with those unexposed [odds ratio (OR) = 1.52; 95% confidence interval (CI) = 1.20-1.92; risk ratio (RR) = 1.17; 95% CI = 1.10-1.25]. We also found a significant decrease in the odds for a live birth among STS-exposed women (OR = 0.75; 95% CI = 0.57-0.99; RR = 0.81; 95% CI = 0.66-0.99).Conclusions: Female STS exposure, estimated through the measurement of cotinine in FF, is associated with an increased risk of implantation failure and reduced odds of a live birth. [ABSTRACT FROM AUTHOR]

The number of in vitro fertilization (IVF) cycles in the United States increased from fewer than 46,000 in 1995 to more than 120,000 in 2005. IVF and other assisted reproductive technology (ART) data are routinely collected and used to identify outcome predictors. However, researchers do not always make full use of the data due to their complexity. Design approaches have included restriction to first-cycle attempts only, which reduces power and identifies effects only of those factors associated with initial success. Many statistical techniques have been used or proposed for analysis of IVF data, ranging from simple t tests to sophisticated models designed specifically for IVF. We applied several of these methods to data from a prospective cohort of 2687 couples undergoing ART from 1994 through 2003. Results across methods are compared and the appropriateness of the various methods is discussed with the intent to illustrate methodologic validity. We observed a remarkable similarity of coefficient estimates across models. However, each method for dealing with multiple cycle data relies on assumptions that may or may not be expected to hold in a given IVF study. The robustness and reported magnitude of effect for individual predictors of IVF success may be inflated or attenuated due to violation of statistical assumptions, and should always be critically interpreted. Given that risk factors associated with IVF success may also advance our understanding of the physiologic processes underlying conception, implantation, and gestation, the application of valid methods to these complex data is critical. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive. OBJECTIVE: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003. METHODS: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders. RESULTS: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (ΣPCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2-3.4) for PCB-153 and 1.7 (1.0-2.9) for ΣPCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450-inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found. CONCLUSIONS: Serum PCB concentrations at levels similar to the U.S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies.Methods: To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses' Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires.Results: During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake [95% confidence interval (CI) = 0.62-0.99; P-value, test for linear trend (Pt) = 0.03]. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17-1.88; Pt = 0.001).Conclusion: These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply. [ABSTRACT FROM AUTHOR]

Background: Regular exercise has been associated with a 40%-80% reduction in risk for endometriosis in several case-control studies. However, women experiencing symptoms prior to their diagnosis may be less likely to exercise than healthy controls, thus biasing the observed association.Methods: Using data collected from the Nurses' Health Study II, a prospective cohort study of premenopausal US nurses that began in 1989, we have attempted to clarify this relation. Data are updated every 2 years with follow-up for these analyses through 2001. In 1989, 1991, and 1997 women reported average amount of time per week engaging in various physical activities. A metabolic equivalent (MET) score was assigned to each activity, and these were summed to estimate total activity.Results: A total of 102,197 premenopausal women contributed 996,422 person-years of follow-up with 2703 cases of laparoscopically confirmed endometriosis. After adjusting for BMI at age 18, current BMI, smoking, parity, infertility status, oral contraceptive use, age at menarche, and menstrual cycle length and pattern in college, we observed only a slight reduction in the incidence of endometriosis, comparing the highest level of activity (>or=42 MET hours/week) to the lowest (<3 MET hours/week) (rate ratio = 0.89 [95% confidence interval = 0.77-1.03]). The association was limited to participants with no past or concurrent infertility (P = 0.002, test for heterogeneity). No associations were seen with inactivity.Conclusions: In this first prospective assessment, we did not find evidence of the strong inverse association previously reported, although we cannot rule out a modest inverse association. [ABSTRACT FROM AUTHOR]

Background: Modifiable risk factors such as diet may be important in both the etiology and progression of endometriosis as well as the prevalence of pain symptoms and infertility associated with this condition. In adults, higher intake of dairy has been associated with a lower risk of endometriosis diagnosis. There is currently no literature on whether dairy intake during adolescence, a potentially critical window of exposure, influences endometriosis risk.Objective: The objectige of the study was to evaluate the association between consumption of dairy foods in adolescence and the risk of laparoscopically confirmed endometriosis.Study Design: This was a prospective cohort study, the Nurses' Health Study II, which has prospectively collected data since 1989. In 1998, when participants were aged 34-51 years, they completed a 124 item food frequency questionnaire about their high school diet. Cases were defined as those who self-reported laparoscopically confirmed endometriosis. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for the association between dairy foods and laparoscopically confirmed endometriosis.Results: Among women who completed the questionnaire about their high school diet in 1998, 581 cases of laparoscopically confirmed endometriosis were diagnosed among 32,868 premenopausal women from 1998 to 2013. Women who consumed more than 4 servings per day of dairy foods during adolescence had a 32% lower risk of laparoscopically confirmed endometriosis during adulthood (95% confidence interval, 0.47-0.96; Ptrend = .04) compared with women consuming 1 or fewer servings per day. The association was similar for low-fat and high-fat dairy foods. Yogurt and ice cream consumption, specifically, were associated with a lower risk of endometriosis. Those who consumed 2 or more servings of yogurt per week as an adolescent had a 29% lower risk of endometriosis diagnosis (95% confidence interval, 0.52-0.97; Ptrend = .02) compared with those consuming less than 1 serving per week. In addition, women who consumed 1 or more servings per day of ice cream per day during adolescence had a 38% lower risk of endometriosis diagnosis (95% confidence interval, 0.40-0.94; Ptrend = .20) compared with those consuming less than 1 serving per week.Conclusion: Our findings suggest that dairy consumption, specifically yogurt and ice cream intake, in adolescence may reduce the risk of subsequent endometriosis diagnosis. Future studies in adolescent populations are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: Pelvic floor pain, abdominal wall pain, and central nervous system pain amplification can be contributing factors in chronic pelvic pain (CPP), however; limited research has investigated the association of pelvic floor, abdominal, and uterine tenderness with central nervous system pain amplification. We assessed whether pressure pain thresholds on the non-dominant thumbnail, a marker of central nervous system pain amplification, were associated with pelvic floor, abdominal, and uterine tenderness among women with endometriosis or CPP.Study Design: We conducted a cross-sectional study among 88 females with endometriosis and/or CPP. Abdominal (6 locations), pelvic floor (6 locations) and uterine (1 location) tenderness were assessed via a standardized physical exam. Participants reported their pain levels (0-10 scale) with application of 2 kg of pressure at each area, with a pain rating of ≥4 on the 0-10 scale considered moderate to severe pain. Pain sensitivity was measured on the non-dominant thumbnail by applying discrete pressure stimuli using a previously validated protocol.Results: Overall, 50% (44/88), 42% (37/88), and 58% (51/88) of participants reported high pelvic floor, abdominal, and uterine tenderness, respectively. Pressure intensities needed to elicit 'faint' and 'mild' pain were lower for participants with high vs. low pelvic floor tenderness (median intensity for 'faint' pain = 0.50 kgf/cm2(min-max:0.25-3.25) vs. 1.06(0.25-3.00), p-value = 0.006; median intensity for 'mild' pain = 2.00(0.63-4.88) vs. 2.63(0.75-6.00), p-value = 0.03). No association was observed between pressure pain sensitivity and abdominal or uterine tenderness (p > 0.11). Participants with endometriosis without pain were less likely to have high pelvic floor (22.2%), abdominal (11.1%), and uterine (25.9%) tenderness compared to participants with endometriosis with pain (63.0%, 50%, 65.2%, respectively) and participants with chronic pelvic pain (60%, 73.3%, 93.3%, respectively).Conclusions: These results suggest that high pelvic floor tenderness among women with endometriosis/CPP may be a marker of heightened pain sensitivity suggestive of central nervous system pain amplification and may impact treatment response. Future research should examine whether this clinical phenotype predicts response to medical and behavioral treatments (e.g, anti-convulsants, behavioral therapy, Physical Therapy). [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether weight change since age 18 years, current body mass index (BMI), and BMI at age 18 years are associated with fecundity.Methods: Our study included 1,950 women in the Nurses' Health Study 3 (2010-2014), a prospective cohort study, currently attempting pregnancy. Height, current weight, and weight at age 18 years were self-reported on the baseline questionnaire. Every 3-6 months thereafter, women reported the current duration of their pregnancy attempt. Multivariable-accelerated failure time models were used to estimate the time ratios and 95% confidence intervals (CIs).Results: For every 5-kg increase in body weight from age 18 years, current duration of pregnancy attempt increased by 5% (95% CI 3-7%). Compared with women who maintained weight, the adjusted median current duration was 0.5 months shorter in those who lost weight, 0.3 months longer for those who gained 4-9.9 kg and 10-19.9 kg, and 1.4 months longer for those who gained 20 kg or more (P trend ≤.001). The adjusted time ratio (95% CI) for a 5-kg/m increase in current BMI was 1.08 (1.04-1.12). After multivariable adjustment (including adjustment for current BMI), being underweight at age 18 years (BMI less than 18.5) was associated with a longer current duration of pregnancy attempt compared with normal-weight women (time ratio 1.25, 95% CI 1.07-1.47); however, being overweight or obese at age 18 years was not associated with fecundity.Conclusion: Gaining weight in adulthood, being overweight or obese in adulthood, and being underweight at age 18 years were associated with a modest reduction in fecundity.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Objective: To identify metabolites in presurgical blood associated with risk of persistent postsurgical pelvic pain 1 year after endometriosis surgery in adolescent and young adult patients.Design: Prospective observational study within the Women's Health Study: From Adolescence to Adulthood, a US-based longitudinal cohort of adolescents and women enrolled from 2012-2018.Setting: Two tertiary care hospitals.Patient(s): Laparoscopically confirmed endometriosis patients (n = 180) with blood collected before their endometriosis surgery. Of these, 77 patients additionally provided blood samples 5 weeks to 6 months after their surgery. We measured plasma metabolites using liquid chromatography tandem mass spectrometry, and a total of 390 known metabolites were included in our analysis.Intervention(s): None.Main Outcome Measure(s): Persistent postsurgical pelvic pain, defined as severe, life-impacting pelvic pain 1 year after endometriosis surgery.Result(s): Most patients (>95%) were at stage I/II of the revised American Society for Reproductive Medicine classification. Their average age at diagnosis was 18.7 years, with 36% reporting persistent postsurgical pelvic pain. Of the 21 metabolites in presurgical blood that were associated with risk of persistent postsurgical pelvic pain, 19 metabolites, which were mainly lipid metabolites, were associated with increased risk. Only 2 metabolites-pregnenolone sulfate (odds ratio = 0.64, 95% confidence interval = 0.44-0.92) and fucose (odds ratio = 0.69, 95% confidence interval = 0.47-0.97)-were associated with decreased risk. Metabolite set enrichment analysis revealed that higher levels of lysophosphatidylethanolamines (false discovery rate = 0.01) and lysophosphatidylcholines (false discovery rate = 0.01) in presurgical blood were associated with increased risk of persistent postsurgical pelvic pain.Conclusion(s): Our results suggest that dysregulation of multiple groups of lipid metabolites may play a role in the persistence of pelvic pain postsurgery among young endometriosis patients. [ABSTRACT FROM AUTHOR]

Objective: To prospectively evaluate the association between dietary fat intake and risk of uterine fibroids; and to evaluate the association between erythrocyte membrane fatty acid (FA) levels and fibroid risk.Design: Prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence interval (CI). In a subset of participants 34 individual FAs were measured and logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI for the association between FA tertiles and fibroids.Setting: Not applicable.Patient(s): Premenopausal US women (81,590) in the Nurses' Health Study II, aged 25-42 years at enrollment in 1989 for whom diet was assessed by a food frequency questionnaire. A total of 553 participants with erythrocyte FA measurements.Intervention(s): Not applicable.Main Outcome Measure(s): Cases of fibroids were defined on the basis of self-reported ultrasound or hysterectomy confirmation.Result(s): A total of 8,142 cases of ultrasound-confirmed or hysterectomy-confirmed were diagnosed during an 18-year period (1991-2009). No associations were observed between intake of any dietary fats and fibroids in the multivariable models. However, when erythrocyte FAs were examined, an inverse association was observed between total n-3 polyunsaturated FAs and likelihood of fibroids (OR for third versus first tertile, 0.41; 95% CI 0.19-0.89). In addition, total trans FAs were associated with more odds of fibroids (OR for third tertile, 3.33; 95% CI 1.50-7.38).Conclusion(s): Our findings provide preliminary suggestions that n-3 polyunsaturated FAs and trans FAs may play a role in fibroid etiology; however, these results should be confirmed in future studies. [ABSTRACT FROM AUTHOR]

Objective: To quantify the effect of medical and obstetrical factors on the odds of cesarean delivery, comparing assisted reproductive technology (ART)-treated women and women with subfertility not treated with ART versus fertile women.Design: Retrospective cohort.Setting: Not applicable.Patient(s): Singleton deliveries to primiparous women; with the source of this data being the Massachusetts vital and hospital records linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System data (2004-2010).Intervention(s): None.Main Outcome Measure(s): Mode of delivery.Result(s): The 173,130 deliveries included 5,768 ART-treated, 2,657 subfertile (1,627 non-ART medically assisted reproduction [MAR] and 1,030 unassisted infertile), and 164,705 fertile pregnancies and 117,743 vaginal and 55,387 cesarean deliveries. ART-treated women were older, more often white and non-Hispanic, and with more private insurance, previous uterine surgery, gestational diabetes, pregnancy hypertension, bleeding, and placental complications than fertile women. Overall rates of cesarean delivery were 45.7%, 43.3%, and 31.1% for ART-treated, subfertile, and fertile women and 41.7% and 45.9% for MAR and unassisted infertile deliveries. When adjusted for demographics, underlying medical factors, previous uterine surgery, and placental and delivery complications, adjusted odds ratios (ORs) compared with fertile women were 1.27 for ART-treated and 1.15 for subfertile women, with greater odds among unassisted infertile (OR 1.26) but not MAR (OR 1.09) women. The strongest confounders of odds of cesarean delivery were age and previous uterine surgery.Conclusion(s): ART and unassisted infertility were associated with greater odds of cesarean compared with fertile women. Underlying medical and obstetrical risks had strong confounding effects strongly attenuating the odds for cesarean delivery. [ABSTRACT FROM AUTHOR]

Background: Preterm delivery has been shown to be associated with increased risk of cardiovascular disease (CVD), but it is unknown whether this risk remains after adjustment for prepregnancy lifestyle and CVD risk factors.Methods: We examined the association between history of having delivered an infant preterm (<37 weeks) and CVD in 70 182 parous women in the Nurses' Health Study II. Multivariable Cox proportional-hazards models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for CVD events (myocardial infarction and stroke, n=949); we also adjusted for intermediates to determine the proportion of the association between preterm and CVD accounted for by postpartum development of CVD risk factors.Results: After adjusting for age, race, parental education, and prepregnancy lifestyle and CVD risk factors, preterm delivery in the first pregnancy was associated with an increased risk of CVD (HR, 1.42; 95% CI, 1.16-1.72) in comparison with women with a term delivery (≥37 weeks) in the first pregnancy. When preterm delivery was split into moderate preterm (≥32 to <37 weeks) and very preterm (<32 weeks), the HRs were 1.22 (95% CI, 0.96-1.54) and 2.01 (95% CI, 1.47-2.75), respectively. The increased rate of CVD in the very preterm group persisted even among women whose first pregnancy was not complicated by hypertensive disorders of pregnancy (HR, 2.01; 95% CI, 1.38-2.93). In comparison with women with at least 2 pregnancies, all of which were delivered at term, women with a preterm first birth and at least 1 later preterm birth had a HR of CVD of 1.65 (95% CI, 1.20-2.28). The association between moderate preterm first birth and CVD was accounted for in part by the development of postpartum chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index (proportion accounted for, 14.5%; 95% CI, 4.0-41.1), as was the very-preterm-CVD relationship (13.1%; 95% CI, 9.0-18.7).Conclusions: Preterm delivery is independently predictive of CVD and may be useful for CVD prevention efforts. Because only a modest proportion of the preterm-CVD association was accounted for by development of conventional CVD risk factors, further research may identify additional pathways. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between laparoscopically confirmed endometriosis and the risk of breast cancer. Previous research on endometriosis and breast cancer has reported mixed results.Methods: Our prospective cohort study included 116,430 women from the Nurses' Health Study II cohort followed from 1989 until 2013. Our primary analysis investigated the association between self-reported laparoscopically confirmed endometriosis and the risk of breast cancer. Breast cancer diagnosis was verified through medical records. Multivariable adjusted Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Breast cancer was further classified by menopausal status at the time of diagnosis and tumor hormone receptor status verified through tissue microarrays when available and medical records.Results: At baseline, 5,389 (5%) women reported laparoscopically confirmed endometriosis. Over 24 years of follow-up, 4,979 (3%) incident breast cancer cases were diagnosed. Women with endometriosis were not at higher risk for overall (adjusted HR 0.96, 95% CI 0.88-1.06), premenopausal (adjusted HR 1.05, 95% CI 0.89-1.23), or postmenopausal breast cancer (adjusted HR 0.93, 95% CI 0.80-1.07). However, associations varied by tumor hormone receptor status (P value, test for heterogeneity: .001), although women with endometriosis were not at increased risk of estrogen- and progesterone receptor-positive (ER+/PR+) tumors (adjusted HR 1.00, 95% CI 0.87-1.14) or ER- and PR- tumors (adjusted HR 0.90, 95% CI 0.67-1.21). Women with endometriosis reported 2.87 ER+/PR- breast cancer cases per 10,000 person-years compared with women without endometriosis (1.32/10,000 person-years), which resulted in nearly a twofold increased risk of ER+/PR- breast cancers (adjusted HR 1.90, 95% CI 1.44-2.50).Conclusion: Endometriosis was not found to be associated with overall risk of breast cancer in this study; however, endometriosis was significantly associated with an increased risk of ER+/PR- breast tumors, which should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Objective: To investigate characteristics of receiving a medical evaluation for infertility among infertile women.Design: Prospective cohort.Setting: Academic institution.Patient(s): A total of 7,422 women who reported incident infertility between 1989 and 2009 in the Nurses' Health Study II.Intervention(s): None.Main Outcome Measure(s): Report of receiving a medical evaluation for infertility.Result(s): Approximately 65% of women who reported infertility had a medical evaluation for infertility. Infertile women who were parous (relative risk [RR] = 0.81, 95% confidence interval [CI] 0.78-0.84), older, current smokers (RR = 0.89, 95% CI 0.83-0.96), or who had a higher body mass index (BMI) were less likely to report receiving a medical infertility evaluation. Infertile women who exercised frequently, took multivitamins (RR = 1.03, 95% CI 1.00-1.07), lived in states with comprehensive insurance coverage (RR = 1.09, 95% CI 1.00-1.19), had a high household income, or who had a recent physical examination (RR = 1.15, 95% CI 1.06-1.24) were more likely to report receiving a medical infertility evaluation.Conclusion(s): These findings highlight demographic, lifestyle, and access barriers to receiving medical infertility care. Historically, the discussion of barriers to infertility care has centered on financial access, geographic access, and socioeconomic status. Our findings build off literature by supporting previously reported associations and showcasing the importance of demographic and lifestyle factors in accessing care. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of cancer after assisted reproductive technology (ART) therapy.Design: Longitudinal cohort study.Setting: Not applicable.Patient(s): New York, Texas, and Illinois residents between 2004 and 2009, treated with ART, comprising cycles of 113,226 women, including 53,859 women without prior ART treatment, who were linked to their respective state cancer registries and whose cycles were reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS).Intervention(s): None.Main Outcome Measure(s): Diagnosis of cancer, as reported to the state cancer registry; standardized incidence ratios (SIR) and their 95% confidence intervals, comparing the observed to expected cancer cases based on age-specific cancer rates in the general population of each state.Result(s): Among the cohort of women without prior ART therapy, hazard ratios (HR) and 95% confidence intervals (CI) were calculated for treatment parameters and reproductive history factors. The mean follow-up period was 4.87 years; among women without prior ART, 450 women developed 460 cancers. Women treated with ART had a statistically significantly lower risk for all cancers (for all women: SIR 0.78; CI, 0.73-0.83; women without prior ART: SIR 0.75; CI, 0.68-0.82), breast cancer, and all female genital cancers; a non-statistically-significant lower risk for endocrine and uterine cancer; and a non-statistically-significant higher risk for melanoma and ovarian cancer. Among women without prior ART, we found no statistically significant increased HR by parity, number of cycles, cumulative follicle-stimulating hormone dosage, or cycle outcome.Conclusion(s): Women initiating ART treatment have no greater risk for developing cancer after nearly 5 years of follow-up compared with the general population and with other women treated with ART. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between regular physical activity and semen quality.Design: Prospective cohort study.Setting: Couples attending one of three IVF clinics in the greater Boston area during 1993-2003. At study entry, male participants completed a questionnaire about their general health, medical history, and physical activity. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using generalized estimating equations models, accounting for potential confounders and multiple samples per man.Patient(s): A total of 2,261 men contributing 4,565 fresh semen samples were enrolled before undergoing their first IVF cycles.Intervention(s): None.Main Outcome Measure(s): Semen volume, sperm concentration, sperm motility, sperm morphology, and total motile sperm (TMS).Result(s): Overall, none of the semen parameters were materially associated with regular exercise. Compared with no regular exercise, bicycling ≥ 5 h/wk was associated with low sperm concentration (OR 1.92, 95% CI 1.03-3.56) and low TMS (OR 2.05, 95% CI 1.19-3.56). These associations did not vary appreciably by age, body mass index, or history of male factor infertility.Conclusion(s): Although the present study suggests no overall association between regular physical activity and semen quality, bicycling ≥ 5 h/wk was associated with lower sperm concentration and TMS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether menstrual and reproductive characteristics may influence development of uterine leiomyomata since sex steroid hormones have been hypothesized to play a role in their development.Design: A prospective cohort study (Nurses' Health Study II).Setting: Participants were identified from 14 states and followed for 14 years.Patient(s): A cohort of 116,609 female registered nurses ages 25-42 at baseline.Intervention(s): We obtained data on uterine leiomyomata incidence and exposures through biennial questionnaires. We calculated hazard ratios and 95% confidence intervals adjusted for known and suspected risk factors.Main Outcome Measure(s): Uterine leiomyomata confirmed by ultrasound or hysterectomy.Result(s): During 1,163,439 person-years of follow-up, 9,847 self-reported cases of hysterectomy- or ultrasound-confirmed uterine leiomyomata were reported. We observed a lower incidence of uterine leiomyomata with later age at menarche, longer menstrual cycles, parity, later age at first and last birth, shorter time since last birth, and breastfeeding.Conclusion(s): Hormonal and anatomical changes associated with menstruation and pregnancy may influence uterine leiomyomata incidence. [ABSTRACT FROM AUTHOR]