545 results on '"Stacey A. Missmer"'
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2. Plasma microRNA expression in adolescents and young adults with endometriosis: the importance of hormone use
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Paula Brady, Abdelrahman Yousif, Naoko Sasamoto, Allison F. Vitonis, Wojciech Fendler, Konrad Stawiski, Mark D. Hornstein, Kathryn L. Terry, Kevin M. Elias, Stacey A. Missmer, and Amy L. Shafrir
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endometriosis ,microRNA ,exogenous hormones ,adolescents ,diagnostic ,Reproduction ,QH471-489 ,Medicine (General) ,R5-920 - Abstract
IntroductionPrior 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.MethodsThe 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.ResultsIn 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
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- 2024
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3. Differences in characteristics and use of complementary and alternative methods for coping with endometriosis-associated acyclic pelvic pain across adolescence and adulthood
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Jennifer M. Mongiovi, Britani Wallace, McKenzie Goodwin, Allison F. Vitonis, Sarah Karevicius, Amy L. Shafrir, Naoko Sasamoto, Amy D. DiVasta, Christine B. Sieberg, Kathryn L. Terry, and Stacey A. Missmer
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endometriosis ,adolescent ,pelvic pain ,complementary therapies ,dysmenorrhea ,pain triggers ,Reproduction ,QH471-489 ,Medicine (General) ,R5-920 - Abstract
IntroductionOver 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.MethodsWe 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 (25 years)] were assessed using Fisher's exact test.ResultsOf 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).DiscussionOur 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.
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- 2024
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4. Visualized peritoneal fluid variation in adolescents and young adults with endometriosis: is there more to it?
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Abdelrahman Yousif, Mary DePari, Allison F. Vitonis, Holly R. Harris, Amy L. Shafrir, Kathryn L. Terry, Stacey A. Missmer, and Naoko Sasamoto
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endometriosis ,peritoneal fluid ,volume ,color ,hormones ,pelvic pain ,Reproduction ,QH471-489 ,Medicine (General) ,R5-920 - Abstract
BackgroundPeritoneal fluid is a medium for endometriosis-associated biomarker discovery from which the local peritoneal environment and pathophysiologic pathways are often inferred. Therefore, we evaluated the associations between peritoneal fluid color and volume at time of endometriosis-related laparoscopic surgery with patient characteristics, endometriosis type and lesion location in adolescents and young adults with endometriosis.MethodsWe conducted a cross-sectional analysis among 545 patients undergoing surgery for endometriosis who enrolled in the Women's Health Study: from Adolescence to Adulthood cohort study. Patient characteristics, surgically visualized endometriosis phenotypes, and gross characteristics of peritoneal fluid were collected in compliance with World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. Chi-square or Fisher's exact tests were applied to test for differences across categories.ResultsMost of the patients were adolescents or young adults (86% age
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- 2023
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5. Accessing medical care for infertility: a study of women in Mexico
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Leslie V. Farland, Sc.D., Sana M. Khan, M.P.H., Stacey A. Missmer, Sc.D., Dalia Stern, Ph.D., Ruy Lopez-Ridaura, M.D., Sc.D., Jorge E. Chavarro, M.D., Sc.D., Andres Catzin-Kuhlmann, M.D., Ana Paola Sanchez-Serrano, M.D., Megan S. Rice, Sc.D., and Martín Lajous, M.D., Sc.D.
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Infertility ,access to care ,fertility treatment ,Diseases of the genitourinary system. Urology ,RC870-923 ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: To investigate barriers in accessing care for infertility in Mexico, because little is known about this issue for low and middle-income countries, which comprise 80% of the world’s population. Design: Cross-sectional analysis. Setting: Mexcian Teachers’ Cohort. Patient(s): A total of 115,315 female public school teachers from 12 states in Mexico. Intervention(s): None. Main Outcome Measure(s): The participants were asked detailed questions about their demographics, lifestyle characteristics, access to the health care system, and infertility history via a self-reported questionnaire. Log-binomial models, adjusted a priori for potential confounding factors, were used to estimate the prevalence ratios (PRs) and 95% confidence intervals ( CIs) of accessing medical care for infertility among women reporting a history of infertility. Result(s): A total of 19,580 (17%) participants reported a history of infertility. Of those who experienced infertility, 12,470 (63.7%) reported seeking medical care for infertility, among whom 8,467 (67.9%) reported undergoing fertility treatments. Among women who reported a history of infertility, women who taught in a rural school (PR, 0.95; 95% CI, 0.92–0.97), spoke an indigenous language (PR, 0.88; 95% CI, 0.84–0.92), or had less than a university degree (PR, 0.93; 95% CI, 0.90–0.97) were less likely to access medical care for fertility. Women who had ever had a mammogram (PR, 1.07; 95% CI, 1.05–1.10), had a pap smear in the past year (PR, 1.08; 95% CI, 1.06–1.10), or who had used private health care regularly or in times of illness were more likely to access medical care for fertility. Conclusion(s): The usage of infertility care varied by demographic, lifestyle, and access characteristics, including speaking an indigenous language, teaching in a rural school, and having a private health care provider.
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- 2023
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6. ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers
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Jake J. Reske, Mike R. Wilson, Brooke Armistead, Shannon Harkins, Cristina Perez, Joel Hrit, Marie Adams, Scott B. Rothbart, Stacey A. Missmer, Asgerally T. Fazleabas, and Ronald L. Chandler
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ARID1A ,SWI/SNF ,H3.3 ,NuRD ,Variant histone ,Chromatin ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background SWI/SNF (BAF) chromatin remodeling complexes regulate lineage-specific enhancer activity by promoting accessibility for diverse DNA-binding factors and chromatin regulators. Additionally, they are known to modulate the function of the epigenome through regulation of histone post-translational modifications and nucleosome composition, although the way SWI/SNF complexes govern the epigenome remains poorly understood. Here, we investigate the function of ARID1A, a subunit of certain mammalian SWI/SNF chromatin remodeling complexes associated with malignancies and benign diseases originating from the uterine endometrium. Results Through genome-wide analysis of human endometriotic epithelial cells, we show that more than half of ARID1A binding sites are marked by the variant histone H3.3, including active regulatory elements such as super-enhancers. ARID1A knockdown leads to H3.3 depletion and gain of canonical H3.1/3.2 at ARID1A-bound active regulatory elements, and a concomitant redistribution of H3.3 toward genic elements. ARID1A interactions with the repressive chromatin remodeler CHD4 (NuRD) are associated with H3.3, and ARID1A is required for CHD4 recruitment to H3.3. ZMYND8 interacts with CHD4 to suppress a subset of ARID1A, CHD4, and ZMYND8 co-bound, H3.3+ H4K16ac+ super-enhancers near genes governing extracellular matrix, motility, adhesion, and epithelial-to-mesenchymal transition. Moreover, these gene expression alterations are observed in human endometriomas. Conclusions These studies demonstrate that ARID1A-containing BAF complexes are required for maintenance of the histone variant H3.3 at active regulatory elements, such as super-enhancers, and this function is required for the physiologically relevant activities of alternative chromatin remodelers.
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- 2022
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7. Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain
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Lysia Demetriou, Michal Krassowski, Pedro Abreu Mendes, Kurtis Garbutt, Allison F. Vitonis, Elizabeth Wilkins, Lydia Coxon, Lars Arendt-Nielsen, Qasim Aziz, Judy Birch, Andrew W. Horne, Anja Hoffman, Lone Hummelshoj, Claire E. Lunde, Jane Meijlink, Danielle Perro, Nilufer Rahmioglu, Kathryn L. Terry, Esther Pogatzki-Zahn, Christine B. Sieberg, Rolf-Detlef Treede, Christian M. Becker, Francisco Cruz, Stacey A. Missmer, Krina T. Zondervan, Jens Nagel, and Katy Vincent
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endometriosis ,pelvic pain ,dyspareunia ,bladder pain syndrome ,dysmennorhoea ,chronic pelvic pain ,Reproduction ,QH471-489 ,Medicine (General) ,R5-920 - Abstract
IntroductionChronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL).MethodsThe study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N = 230) and four pain groups: endometriosis-associated pain (EAP, N = 237), interstitial cystitis/bladder pain syndrome (BPS, N = 72), comorbid endometriosis-associated pain and BPS (EABP, N = 120), and pelvic pain only (PP, N = 127).ResultsClinical profiles of women with CPP (13–50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p
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- 2023
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8. Infertility and Risk of Cardiovascular Disease: A Prospective Cohort Study
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Leslie V. Farland, Yi‐Xin Wang, Audrey J. Gaskins, Janet W. Rich‐Edwards, Siwen Wang, Maria Christine Magnus, Jorge E. Chavarro, Kathryn M. Rexrode, and Stacey A. Missmer
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cardiovascular disease ,coronary heart disease ,endometriosis ,infertility ,myocardial infarction ,polycystic ovary syndrome ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Certain symptoms associated with infertility are associated with cardiovascular disease, including menstrual cycle irregularity, early menopause, and obesity; however, few studies have investigated the association between infertility and cardiovascular disease risk. Methods and Results Participants in the NHSII (Nurses' Health Study II) who reported infertility (12 months of trying to conceive without success, including women who subsequently conceived) or who were gravid, with no infertility were followed from 1989 until 2017 for development of incident, physician‐diagnosed coronary heart disease (CHD) (myocardial infarction, coronary artery bypass grafting, angioplasty, stent) and stroke. Time‐varying Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs and were adjusted a priori for potential confounding variables. Among 103 729 participants, 27.6% reported having ever experienced infertility. Compared with gravid women who had not reported infertility, women with a history of infertility had greater risk of CHD (HR, 1.13 [95% CI, 1.01–1.26]) but not stroke (HR, 0.91 [95% CI, 0.77–1.07]). The association between history of infertility and CHD was strongest among women who reported infertility at an earlier age (HR for infertility first reported at ≤25 years, 1.26 [95% CI, 1.09–1.46]; HR at 26–30 years, 1.08 [95% CI, 0.93–1.25]; HR at >30 years, 0.91 [95% CI, 0.70–1.19]). When we investigated specific infertility diagnoses, elevated risk of CHD was observed among women whose infertility was attributed to an ovulatory disorder (HR, 1.28 [95% CI, 1.05–1.55]) or endometriosis (HR, 1.42 [95% CI, 1.09–1.85]). Conclusions Women with infertility may be at an increased risk of CHD. Risk differed by age at first infertility diagnosis and was restricted to ovulatory‐ and endometriosis‐related infertility.
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- 2023
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9. Breastfeeding duration and subsequent risk of mortality among US women: A prospective cohort study
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Yi-Xin Wang, Mariel Arvizu, Janet W. Rich-Edwards, JoAnn E. Manson, Liang Wang, Stacey A. Missmer, and Jorge E. Chavarro
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Breastfeeding duration ,Mortality ,Cohort study ,Women's health ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Breastfeeding has been associated with a reduced maternal long-term risk of chronic diseases, but its association with mortality is poorly known. Methods: We included 166,708 female United States (US) nurses from the Nurses’ Health Study (1986-2016) and the Nurses’ Health Study II (1989-2019) who experienced at least one pregnancy lasting at least six months across their reproductive lifespan. Hazard ratios and 95% confidence intervals (CI) for mortality according to lifetime breastfeeding duration were estimated with time-dependent Cox proportional hazards regression models. Findings: During 4,705,160 person-years of follow-up, 36,634 deaths were documented in both cohorts, including 9880 from cancer and 7709 from cardiovascular disease (CVD). Lifetime total breastfeeding duration was associated with a lower subsequent risk of all-cause mortality in a non-linear manner (p-value for non-linearity=0.0007). The pooled multivariable-adjusted hazard ratios of all-cause mortality were 0.95 (95% CI: 0.92 to 0.98), 0.94 (95% CI: 0.91 to 0.98), 0.93 (95% CI: 0.90 to 0.97), and 0.93 (95% CI: 0.89 to 0.97), respectively, for women reporting lifetime total breastfeeding duration of 4–6, 7–11, 12–23, and ≥24 months, compared to women who breastfed for ≤3 months over their reproductive lifespan. Cause-specific analysis showed a similar pattern of non-linear inverse associations between lifetime total breastfeeding duration and CVD and cancer mortality (both p-values for non-linearity
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- 2022
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10. Association of infertility with premature mortality among US women: Prospective cohort study
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Yi-Xin Wang, Leslie V. Farland, Siwen Wang, Audrey J. Gaskins, Liang Wang, Janet W. Rich-Edwards, Rulla Tamimi, Stacey A. Missmer, and Jorge E. Chavarro
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Infertility, Premature mortality, Women, Public health ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Infertility has been associated with common chronic non-communicable diseases. However, the association of infertility with long-term mortality is unclear. Methods: We followed 101,777 women aged 25–42 years at enrollment between 1989 and 2017. Biennial questionnaires updated participants’ infertility status and underlying reasons for infertility throughout their reproductive lifespan. Hazard ratios (HRs) for the associations of infertility with the risk of premature mortality (death before age 70 years) were estimated using Cox proportional hazards models. Findings: During 28 years of follow-up, 2174 women died before age 70 years. Infertility was associated with an HR of 1.26 (95% confidence interval: 1.15 to 1.38) for premature death. This relation was largely driven by deaths from cancer (HR = 1.22, 1.08 to 1.39) and was stronger among women reporting infertility at a younger age (HR = 1.35, 1.19 to 1.52 for age ≤ 25 years; 1.23, 1.10 to 1.38 for age 26–30 years; and 1.10, 0.91 to 1.32 for age > 30 years, compared to no infertility). The premature mortality risk was also higher for women who didn't become pregnant after their first report of infertility (HR = 1.39, 1.25 to 1.54) than among women who reported at least one pregnancy after infertility (HR = 1.12, 1.00 to 1.26). When contributing diagnoses of infertility were evaluated, a greater risk of all-cause mortality was associated with infertility due to ovulatory disorders (HR = 1.28, 1.09 to 1.51) and endometriosis (HR = 1.50, 1.22 to 1.83). Interpretation: Infertility may be associated with a greater risk of premature mortality, particularly cancer mortality. Funding: The National Institutes of Health grants.
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- 2022
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11. Editorial: COVID-19 and Women's Health
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Laura A. Magee, Vassiliki Benetou, Rhiannon George-Carey, Jayashri Kulkarni, Nathalie Emma MacDermott, Stacey A. Missmer, Chelsea Morroni, Marianne Vidler, and Stephen H. Kennedy
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women's health ,COVID-19 ,pregnancy ,pandemic consequences ,gender equality in health ,Gynecology and obstetrics ,RG1-991 ,Women. Feminism ,HQ1101-2030.7 - Published
- 2022
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12. Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway
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Amanda R. Markovitz, Eirin B. Haug, Julie Horn, Abigail Fraser, Corrie Macdonald-Wallis, Kate Tilling, Eric B. Rimm, Stacey A. Missmer, Paige L. Williams, Pål R. Romundstad, Bjørn O. Åsvold, and Janet W. Rich-Edwards
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parity ,cholesterol ,high density lipoprotein ,triglycerides ,epidemiology ,spline ,Biochemistry ,QD415-436 - Abstract
We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trøndelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by −4.2 mg/dl (95% CI: −5.0, −3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (−1.4 mg/dl; 95% CI: −2.3, −0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy.
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- 2018
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13. Prevalence of Common Gynecological Conditions in the Middle East: Systematic Review and Meta-Analysis
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Mira Mousa, Moamar Al-Jefout, Habiba Alsafar, Shona Kirtley, Cecilia M. Lindgren, Stacey A. Missmer, Christian M. Becker, Krina T. Zondervan, and Nilufer Rahmioglu
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gynecological disease ,epidemiology ,global health ,Middle East ,polycystic ovary syndrome ,endometriosis ,Reproduction ,QH471-489 ,Medicine (General) ,R5-920 - Abstract
Introduction: High prevalence of gynecological conditions in women of Middle Eastern origin is reported, likely due to regional risk factors and mediators. The objective of this systematic review and meta-analysis is to investigate the prevalence of polycystic ovary syndrome (PCOS), endometriosis, uterine fibroids, and adenomyosis in women of Middle Eastern origin.Methods: MEDLINE, EMBASE, PsycINFO, Global Health, and Google Scholar databases were searched from database inception until 14 February 2021 to identify relevant studies. Peer-reviewed research articles that reported the prevalence of PCOS, endometriosis, uterine fibroids, and adenomyosis in the Middle Eastern population were written in English or Arabic. The primary outcome was the estimated pooled prevalence of PCOS, endometriosis, uterine fibroids, and adenomyosis in the Middle Eastern populations. The secondary outcome was to assess the evidence in the data for the presence of heterogeneity, by conducting subtype-pooled analysis of prevalence estimates of the conditions. Total weighted prevalence was calculated via Freeman–Tukey arcsine transformation and heterogeneity through the I2 statistic. Quality control was performed using GRADE criteria.Results: A total of 47 studies, 26 on PCOS, 12 on endometriosis, eight on uterine fibroids, and seven on adenomyosis, were included. The pooled prevalence of PCOS diagnosed according to the NIH criteria was 8.9% (95% CI: 6.5–11.7; prevalence range: 4.0–27.6%), with a higher prevalence from the Gulf Arab states (18.8%, 95% CI: 9.5–30.3; range: 12.1–27.6%). According to the Rotterdam criteria, the pooled prevalence of PCOS was 11.9% (95% CI: 7.1–17.7; range: 3.4–19.9%) with studies limited to the Persian and Levant regions. Endometriosis was diagnosed in 12.9% (95% CI: 4.2–25.4; range: 4.2–21.0%) of women undergoing laparoscopy, for any indication. Uterine fibroid and adenomyosis prevalence of women was 30.6% (95% CI: 24.9–36.7; range: 18.5–42.6%) and 30.8% (95% CI: 27.1–34.6, range: 25.6–37.7%), respectively. Heterogeneity was present between studies due to statistical and methodological inconsistencies between studies, and quality of evidence was low due to sample size and unrepresentative participant selection.Conclusion: This is the first review that has reported the prevalence of gynecological diseases in the Middle Eastern population, suggesting that gynecological morbidity is a public health concern. Due to the health disparities in women, further research is required to understand the relative roles of environmental and genetic factors in the region to serve as a benchmark for evaluation and comparative purposes with other populations.
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- 2021
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14. Protocol for the Cultural Translation and Adaptation of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project Endometriosis Participant Questionnaire (EPHect)
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Cise Mis, Gokcen Kofali, Bethan Swift, Pinar Yalcin Bahat, Gamze Senocak, Bahar Taneri, Lone Hummelshoj, Stacey A. Missmer, Christian M. Becker, Krina T. Zondervan, Bahar Yuksel Ozgor, Engin Oral, Umit Inceboz, Mevhibe B. Hocaoglu, and Nilufer Rahmioglu
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endometriosis ,standardization ,harmonization ,Turkish ,questionnaire ,EPHect ,Gynecology and obstetrics ,RG1-991 ,Women. Feminism ,HQ1101-2030.7 - Abstract
Endometriosis affects 10% of women worldwide and is one of the most common causes of chronic pelvic pain and infertility. However, causal mechanisms of this disease remain unknown due to its heterogeneous presentation. In order to successfully study its phenotypic variation, large sample sizes are needed. Pooling of data across sites is not always feasible given the large variation in the complexity and quality of the data collected. The World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect) have developed an endometriosis participant questionnaire (EPQ) to harmonize non-surgical clinical participant characteristic data relevant to endometriosis research, allowing for large-scale collaborations in English-speaking populations. Although the WERF EPHect EPQs have been translated into different languages, no study has examined the cross-cultural translation and adaptation for content and face validity. In order to investigate this, we followed the standard guidelines for cross-cultural adaptation and translation of the minimum version of the EPQ (EPQ-M) using 40 patients who underwent laparoscopic surgery in Turkey and 40 women in Northern Cyprus, aged between 18 and 55. We assessed the consistency by using cognitive testing and found the EPHect EPQ-M to be comprehensive, informative, and feasible in these two Turkish-speaking populations. The translated and adapted questionnaire was found to be epidemiologically robust, taking around 30–60 min to complete; furthermore, participants reported a similar understanding of the questions, showing that common perspectives were explored. Results from the cognitive testing process led to minor additions to some items such as further descriptive and/or visuals in order to clarify medical terminology. This paper illustrates the first successful cross-cultural translation and adaptation of the EPHect EPQ-M and should act as a tool to allow for further studies that wish to use this questionnaire in different languages. Standardized tools like this should be adopted by researchers worldwide to facilitate collaboration and aid in the design and conduction of global studies to ultimately help those affected by endometriosis and its associated symptoms.
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- 2021
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15. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism
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Yadav Sapkota, Valgerdur Steinthorsdottir, Andrew P. Morris, Amelie Fassbender, Nilufer Rahmioglu, Immaculata De Vivo, Julie E. Buring, Futao Zhang, Todd L. Edwards, Sarah Jones, Dorien O, Daniëlle Peterse, Kathryn M. Rexrode, Paul M. Ridker, Andrew J. Schork, Stuart MacGregor, Nicholas G. Martin, Christian M. Becker, Sosuke Adachi, Kosuke Yoshihara, Takayuki Enomoto, Atsushi Takahashi, Yoichiro Kamatani, Koichi Matsuda, Michiaki Kubo, Gudmar Thorleifsson, Reynir T. Geirsson, Unnur Thorsteinsdottir, Leanne M. Wallace, iPSYCH-SSI-Broad Group, Jian Yang, Digna R. Velez Edwards, Mette Nyegaard, Siew-Kee Low, Krina T. Zondervan, Stacey A. Missmer, Thomas D'Hooghe, Grant W. Montgomery, Daniel I. Chasman, Kari Stefansson, Joyce Y. Tung, and Dale R. Nyholt
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Science - Abstract
Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.
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- 2017
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16. Pelvic pain symptoms and endometriosis characteristics in relation to oxidative stress among adolescents and adults with and without surgically-confirmed endometriosis [version 1; peer review: awaiting peer review]
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Amy L Shafrir, Britani Wallace, Ashley Laliberte, Allison F Vitonis, Christine B Sieberg, Kathryn L Terry, and Stacey A Missmer
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Research Article ,Articles ,oxidative stress ,dysmenorrhea ,pelvic pain ,dyspareunia ,endometriosis ,endometriotic lesions - Abstract
Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-linked immunosorbent assay, we measured 8-Hydroxy-2’-deoxyguanosine (8-OHdG) in urine samples and corrected for creatinine levels in 434 surgically-confirmed endometriosis participants compared to 605 participants never diagnosed with endometriosis. At enrollment, participants reported details of their pelvic pain symptoms. Linear regression was used to compute geometric mean (GM) creatinine-corrected 8-OHdG levels with 95% confidence intervals (CI) among all participants and those with and without endometriosis separately, adjusting for potential confounders. Interactions by surgically-confirmed endometriosis status were tested by Wald statistics. Results: No trends in 8-OHdG were observed among those with or without endometriosis for severity or frequency of dysmenorrhea, acyclic pelvic pain, dyspareunia or pain with bowel movements. Among endometriosis participants, lower 8-OHdG levels were observed for participants with any white, blue/black, or brown lesions (GM=76.7 versus 82.9 ng/mg; p=0.10), which was primarily driven by lower levels of 8-OHdG for any blue/black lesions (GM=72.8 versus 81.6 ng/mg; p=0.05). Conclusion: While no associations were observed between 8-OHdG and pelvic pain symptoms, future research is needed to assess how other pathways of oxidative damage, e.g. through proteins or lipids, may affect endometriosis-associated symptoms. Additionally, further research is needed to understand differences in oxidative stress among endometriosis lesion sub-phenotypes.
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- 2024
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17. Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study
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Leslie V. Farland, William J. Degnan, Melanie L. Bell, Scott E. Kasner, Ava L. Liberman, Divya K. Shah, Kathryn M. Rexrode, and Stacey A. Missmer
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Advanced and Specialized Nursing ,Adult ,Adolescent ,Aspirin ,Anti-Inflammatory Agents, Non-Steroidal ,Endometriosis ,Middle Aged ,Hormones ,Cohort Studies ,Stroke ,Pregnancy ,Risk Factors ,Infertility ,Humans ,Female ,Neurology (clinical) ,Prospective Studies ,Cardiology and Cardiovascular Medicine ,Contraceptives, Oral - Abstract
Background: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. Methods: Participants in the NHSII cohort study (Nurses’ Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (≥ 50 years), infertility history, body mass index (≥ 25 kg/m 2 ), and menopausal status. Results: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10–1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%–71%]) and hormone therapy (16% mediated [95% CI, 5%–40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status. Conclusions: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.
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- 2023
18. A discrete-choice experiment study of physicians’ prioritization of attributes of medical treatments for endometriosis-associated pain
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Christine Poulos, Yanqing Xu, Willings Botha, Colton Leach, Kristin Kahle Wrobleski, Keith Gordon, Stacey A. Missmer, and Stephanie J. Estes
- Subjects
Health Policy ,Pharmacology (medical) ,General Medicine - Published
- 2023
19. Endogenous Steroid Hormone Concentrations and Risk of Endometriosis in Nurses’ Health Study II
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Amy L Shafrir, Fan Mu, A Heather Eliassen, Madhavi Thombre Kulkarni, Kathryn L Terry, Susan E Hankinson, and Stacey A Missmer
- Subjects
Epidemiology - Abstract
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.
- Published
- 2022
20. Pesticide residue intake from fruit and vegetable consumption and risk of laparoscopically confirmed endometriosis
- Author
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Nichole A. Garzia, Kara Cushing-Haugen, Yu-Han Chiu, Helena Sandoval-Insausti, Jorge E. Chavarro, Stacey A. Missmer, and Holly R. Harris
- Subjects
Adult ,Embryology ,Adolescent ,Reproductive Medicine ,Fruit ,Vegetables ,Pesticide Residues ,Endometriosis ,Humans ,Female ,Prospective Studies ,Pesticides - Abstract
To examine the association between the intake of fruits and vegetables with high- vs. low-pesticide residue burden and diagnosis of laparoscopically confirmed endometriosis. The etiology of endometriosis is not well understood, but dietary factors may influence the risk. Pesticides may act as endocrine disruptors, and the intake of pesticide-contaminated food is a common exposure pathway.Prospective cohort study. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazard models to evaluate the intake of fruits and vegetables with high- and low-pesticide residues in relation to the diagnosis of laparoscopically confirmed endometriosis.Not applicable.Premenopausal US women (N = 52,053) of the Nurses' Health Study II, aged 34-53 years at study baseline (1999), were followed until 2013. The diet was assessed every 4 years using a validated food frequency questionnaire. A previously developed and validated pesticide residue burden score (PRBS), on the basis of the US Department of Agriculture Pesticide Data Program, was used to assign fruits and vegetables to pesticide residue groups (high/low).Not applicable.Cases of laparoscopically confirmed endometriosis were identified from self-reports to validated questionnaires.During 14 years of follow-up, 956 incidences of laparoscopically confirmed endometriosis were reported. No association was observed between the intake of high- or low-PRBS fruit and vegetable intake and endometriosis (hazard ratio for 5th vs. 1st quintile: high-PRBS intake = 0.94, 95% confidence interval = 0.73-1.23; low-PRBS intake = 1.07, 95% confidence interval = 0.82-1.40). No associations were observed for high- or low-PRBS fruit and vegetable intake by fertility status.No clear associations were observed between high- or low-PRBS fruit and vegetable intake and endometriosis risk among premenopausal women. To our knowledge, this is the first study to evaluate the association between dietary pesticide residue intake and endometriosis. Further research is needed, particularly to evaluate this association among a younger population of women (adolescence or early adulthood) and assess the dietary exposure to specific pesticides or chemical families.
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- 2022
21. Assisted reproductive technology or infertility: What underlies adverse outcomes? Lessons from the Massachusetts Outcome Study of Assisted Reproductive Technology
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Judy E. Stern, Leslie V. Farland, Sunah S. Hwang, Dmitry Dukhovny, Charles C. Coddington, Howard J. Cabral, Stacey A. Missmer, Eugene Declercq, and Hafsatou Diop
- Abstract
Numerous studies have demonstrated that assisted reproductive technology (ART: defined here as including only
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- 2022
22. Polycystic ovary syndrome and risk of adverse pregnancy outcomes: a registry linkage study from Massachusetts
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Leslie V. Farland, Sunah S. Hwang, Stacey A. Missmer, Charles C. Coddington, Hafsatou Diop, Judy E. Stern, Howard Cabral, Chia-Ling Liu, and Dmitry Dukhovny
- Subjects
medicine.medical_specialty ,China ,Adolescent ,Placenta ,Endometriosis ,Pre-Eclampsia ,Pregnancy ,medicine ,Humans ,Registries ,Pregnancy outcomes ,Linkage (software) ,Obstetrics ,business.industry ,Cesarean Section ,Rehabilitation ,Infant, Newborn ,Pregnancy Outcome ,Obstetrics and Gynecology ,General Medicine ,Polycystic ovary ,United States ,Pregnancy Complications ,Diabetes, Gestational ,Reproductive Medicine ,Cardiovascular Diseases ,Infertility ,Premature Birth ,Female ,business ,Polycystic Ovary Syndrome - Abstract
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 ( 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 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.
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- 2022
23. Glycemic Index, Glycemic Load, Fiber, and Gluten Intake and Risk of Laparoscopically Confirmed Endometriosis in Premenopausal Women
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Naomi R M Schwartz, Myriam C Afeiche, Kathryn L Terry, Leslie V Farland, Jorge E Chavarro, Stacey A Missmer, and Holly R Harris
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Adult ,Dietary Fiber ,Nutrition and Dietetics ,Glutens ,Endometriosis ,Glycemic Load ,Medicine (miscellaneous) ,Glycemic Index ,Risk Factors ,Vegetables ,Dietary Carbohydrates ,Humans ,Female ,Prospective Studies ,Original Research Article ,Edible Grain - Abstract
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; P(trend) = 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; P(trend) = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; P(trend) = 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; P(trend) = 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.
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- 2022
24. Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis
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Naoko, Sasamoto, Amy L, Shafrir, Britani M, Wallace, Allison F, Vitonis, Cameron J, Fraer, Jenny, Sadler Gallagher, Mary, DePari, Marzieh, Ghiasi, Marc R, Laufer, Christine B, Sieberg, Amy D, DiVasta, Andrew, Schrepf, Sawsan, As-Sanie, Kathryn L, Terry, and Stacey A, Missmer
- Subjects
Anesthesiology and Pain Medicine ,Neurology ,Neurology (clinical) - Abstract
We described trends in pelvic pain characteristics over 2 years of follow-up among adolescents and adults with and without endometriosis participating in the longitudinal observational cohort of the Women's Health Study: From Adolescence to Adulthood, using data reported at baseline and at years 1 and 2 of follow-up. Participants completed a questionnaire at baseline (between November 2012 and May 2019) and annually thereafter that included validated measures of severity, frequency, and life interference of dysmenorrhea, acyclic pelvic pain, and dyspareunia. Our study population included 620 participants with surgically confirmed endometriosis (rASRM stage I/II = 95%) and 671 community-based and hospital-based controls, with median age = 19 and 24 years, respectively. The proportion reporting hormone use varied across the 3 years ranging from 88% to 92% for cases and 56% to 58% for controls. At baseline, endometriosis cases were more likely to report severe, frequent, and life-interfering dysmenorrhea, acyclic pelvic pain, and dyspareunia compared with controls. Among cases, frequency and severity of dysmenorrhea and dyspareunia were relatively static across 2 years. However, acyclic pelvic pain improved. Severe acyclic pain decreased from 69% at baseline to 46% at year 2. Daily pain decreased from 28% to 14%, and life interference from 68% to 38%. Trends among controls remained fairly stable across 2 years. Among endometriosis cases who completed the questionnaire at all 3 time points, 18% reported persistent, severe acyclic pelvic pain at all 3 time points. Over time, different trends were observed by pelvic pain type among endometriosis cases and controls, supporting the importance of assessing multidimensional features of pelvic pain.
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- 2022
25. Hysterectomy With and Without Oophorectomy, Tubal Ligation, and Risk of Cardiovascular Disease in the Nurses' Health Study II
- Author
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Leslie V. Farland, Megan S. Rice, William J. Degnan, Kathryn M. Rexrode, JoAnn E. Manson, Eric B. Rimm, Janet Rich-Edwards, Elizabeth A. Stewart, Sarah L. Cohen Rassier, Whitney R. Robinson, and Stacey A. Missmer
- Subjects
General Medicine - Published
- 2023
26. Circulating proteomic profiles associated with endometriosis in adolescents and young adults
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Naoko Sasamoto, Long Ngo, Allison F Vitonis, Simon T Dillon, Stacey A Missmer, Towia A Libermann, and Kathryn L Terry
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Adult ,Proteomics ,Adolescent ,Rehabilitation ,Endometriosis ,Obstetrics and Gynecology ,Original Articles ,United States ,Cohort Studies ,Observational Studies as Topic ,Young Adult ,Cross-Sectional Studies ,Reproductive Medicine ,Humans ,Female ,Boston - Abstract
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 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 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 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.
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- 2022
27. Presurgical blood metabolites and risk of postsurgical pelvic pain in young patients with endometriosis
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Naoko Sasamoto, Oana A. Zeleznik, Allison F. Vitonis, Stacey A. Missmer, Marc R. Laufer, Julian Avila-Pacheco, Clary B. Clish, and Kathryn L. Terry
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Reproductive Medicine ,Obstetrics and Gynecology - Published
- 2022
28. Data from Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women
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Susan E. Hankinson, Stacey A. Missmer, A. Heather Eliassen, Shelley S. Tworoger, and Margaret A. Gates
- Abstract
Prior epidemiologic studies suggest that regular use of analgesics may decrease risk of breast and ovarian cancer. We explored possible hormone-mediated mechanisms for these associations by examining the relationship between use of aspirin, nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), and acetaminophen and sex steroid hormone concentrations among 740 postmenopausal women in the Nurses' Health Study. All women reported their analgesic use in 1988 or 1990 and provided a blood sample in 1989 to 1990. We calculated adjusted geometric mean estrogen and androgen levels for each category of analgesic use and calculated the P value for trend with increasing frequency of use. There was no association between days of use per month of aspirin, nonaspirin NSAIDs, or acetaminophen in 1990 and hormone levels (all Ptrend ≥ 0.09). However, we observed significant inverse trends between the estimated number of aspirin tablets per month in 1988 and concentrations of estrone (Ptrend = 0.04) and estrone sulfate (Ptrend = 0.03). In analyses of total (aspirin and nonaspirin) NSAID use in 1990, women who used NSAIDs at least 15 days per month had significantly lower levels of estradiol compared with women with no NSAID use (Ptrend = 0.03). Frequency of use of all analgesics (aspirin, nonaspirin NSAIDs, and acetaminophen) in 1990 was inversely associated with concentrations of estradiol (Ptrend = 0.001), free estradiol (Ptrend = 0.01), estrone sulfate (Ptrend = 0.03), and the ratio of estradiol to testosterone (Ptrend = 0.04). Among postmenopausal women, regular users of aspirin and other analgesics may have lower estrogen levels than nonusers, which could contribute to a decreased risk of breast or ovarian cancer among analgesic users. Cancer Epidemiol Biomarkers Prev; 19(4); 1033–41. ©2010 AACR.
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- 2023
29. Supplementary Table 1 from Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women
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Susan E. Hankinson, Stacey A. Missmer, A. Heather Eliassen, Shelley S. Tworoger, and Margaret A. Gates
- Abstract
Supplementary Table 1 from Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women
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- 2023
30. Supplementary Table 2 from Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women
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Susan E. Hankinson, Stacey A. Missmer, A. Heather Eliassen, Shelley S. Tworoger, and Margaret A. Gates
- Abstract
Supplementary Table 2 from Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women
- Published
- 2023
31. Association of laparoscopically-confirmed endometriosis with long COVID-19: a prospective cohort study
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Siwen Wang, Leslie V. Farland, Audrey J. Gaskins, Jasmine Mortazavi, Yi-Xin Wang, Rulla M. Tamimi, Janet W. Rich-Edwards, Dan Zhang, Kathryn L. Terry, Jorge E. Chavarro, and Stacey A. Missmer
- Subjects
Obstetrics and Gynecology - Published
- 2023
32. A prospective cohort study of infertility and cancer incidence
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Siwen Wang, Audrey J. Gaskins, Leslie V. Farland, Dan Zhang, Brenda M. Birmann, Janet W. Rich-Edwards, Yi-Xin Wang, Rulla M. Tamimi, Stacey A. Missmer, and Jorge E. Chavarro
- Subjects
Reproductive Medicine ,Obstetrics and Gynecology - Published
- 2023
33. Association between endometriosis and lower urinary tract symptoms
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Iwona Gabriel, Allison F. Vitonis, Stacey A. Missmer, Ayòtúndé Fadayomi, Amy D. DiVasta, Kathryn L. Terry, and Vatche A. Minassian
- Subjects
Adult ,Cross-Sectional Studies ,Adolescent ,Lower Urinary Tract Symptoms ,Reproductive Medicine ,Surveys and Questionnaires ,Urinary Incontinence, Stress ,Endometriosis ,Humans ,Obstetrics and Gynecology ,Female - Abstract
To determine if women with endometriosis experience lower urinary tract symptoms (LUTSs) more often than those without.Cross-sectional analysis at enrollment in a longitudinal cohort.Enrollment at 2 academic hospitals and from the local community.This analysis included 1,161 women with (n = 520) and without (n = 641) surgically confirmed endometriosis who were enrolled in the Women's Health Study: from Adolescence to Adulthood between 2012 and 2018.Not applicable.Prevalence of LUTSs, including stress incontinence, urgency and frequency, straining with urination, incomplete bladder emptying, hematuria, dysuria, and bladder pain using standardized questionnaires.The primary outcomes were that women with endometriosis reported the following more often than those without: difficulty passing urine (7.9% vs. 2%; crude odds ratio [OR], 4.14 [95% confidence interval {CI}, 2.19-7.80]; adjusted OR [aOR], 4.31 [95% CI, 2.07-8.95]); still feeling full after urination (18.8% vs. 4.7%; crude OR, 4.73 [95% CI, 3.08-7.25]; aOR, 4.67 [95% CI, 2.88-7.56]); having to urinate again within minutes of urinating (33.1% vs. 17.0%; crude OR, 2.41 [95% CI, 1.83-3.18]; aOR, 2.49 [95% CI, 1.81-3.43]), dysuria (11.7% vs. 4.9%; crude OR, 2.55 [95% CI, 1.62-4.01]; aOR, 2.38 [95% CI, 1.40-4.02]); and pain when the bladder is full (23.0% vs. 4.9%; crude OR, 5.79 [95% CI, 3.82-8.78]; aOR, 6.04 [95% CI, 3.74-9.76]). For the secondary outcomes, among female participants with endometriosis, we observed that the odds of LUTS did not differ by the revised American Society for Reproductive Medicine stage (I/II vs. III/IV) or duration of endometriosis-associated symptoms.Women with surgically confirmed endometriosis were more likely to report LUTS than those without.
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- 2022
34. Hospitalizations up to 8 years following delivery in assisted reproductive technology-treated and subfertile women
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Leslie V, Farland, Chia-Ling, Liu, Hafsatou, Diop, Howard J, Cabral, Stacey A, Missmer, Charles C, Coddington, Sunah S, Hwang, and Judy E, Stern
- Subjects
Adult ,Reproductive Techniques, Assisted ,Infant, Newborn ,Obstetrics and Gynecology ,Delivery, Obstetric ,Article ,Cohort Studies ,Hospitalization ,Massachusetts ,Reproductive Medicine ,Pregnancy ,Humans ,Female ,Infertility, Female ,Retrospective Studies - Abstract
OBJECTIVE: To investigate hospitalizations up to 8 years after livebirth among women who utilized ART or who were subfertile, compared to women who conceived naturally. DESIGN: Retrospective cohort SETTING: Massachusetts deliveries among privately insured women ≥18 years old between 2004–2017 from state vital records were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS), and hospital observational/inpatient stays. PATIENTS: We compared patients with ART, medically assisted reproduction, and unassisted subfertile delivery to fertile delivery. INTERVENTION: NA MAIN OUTCOME MEASURED: Post-delivery hospitalization information was derived from ICD codes for discharges and were combined by type. The relative risks (RR) and 95% confidence intervals (CI) of hospitalization for up to the first 8 years post-delivery were modeled. RESULTS: Among 492,515 deliveries, 5.6% used ART, 1.6% used medically assisted reproduction, and 1.8% were unassisted subfertile. Compared to fertile deliveries, deliveries that utilized ART, medically assisted reproduction or were unassisted subfertile were more likely to have hospital utilization (inpatient or observational stay) for any reason for up to 8 years of follow-up (unassisted subfertile aRR:1.18 (1.12–1.25); medically assisted reproduction:1.20 (1.13–1.27); ART aRR:1.29 (1.25–1.34)). ART deliveries had an increased risk of hospitalization for conditions of the cardiovascular system(aRR: 1.31 (1.20–1.41)), overweight/obesity(aRR:1.30 (1.17–1.44)), diabetes(aRR:1.25 (1.05–1.49)), reproductive tract(aRR:1.62 (1.47–1.79)), digestive tract(aRR:1.39 (1.30–1.49), thyroid(aRR:2.02 (1.80–2.26)), respiratory system(aRR: 1.13 (1.03–1.24)), and cancer(aRR:1.40 (1.18–1.65)) up to 8 years after delivery. Deliveries with medically assisted reproduction and subfertility had similar patterns of hospitalization as ART deliveries. CONCLUSION: Women who conceived through fertility treatment or who experienced subfertility were at an increased risk for subsequent hospitalization resulting from a variety of chronic and acute conditions. FUNDING: NIH R01HD067270
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- 2022
35. Endometriosis and Pelvic Pain for the Gastroenterologist
- Author
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Sukhbir S, Singh, Stacey A, Missmer, and Frank F, Tu
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Dyspareunia ,Dysmenorrhea ,Gastroenterologists ,Endometriosis ,Gastroenterology ,Humans ,Female ,Laparoscopy ,Pelvic Pain - Abstract
Endometriosis, affecting 5-10% of reproductive-age women, is a common contributor to dysmenorrhea and chronic pelvic pain. Diagnosis requires laparoscopic tissue biopsy, but careful pelvic examination, and/or imaging with either ultrasound or MRI, may identify patients who should receive empiric first-line therapy. The presence of dyschezia, particularly with cyclical exacerbation, should raise suspicion for bowel or rectovaginal septum involvement, and a greater need for surgical management. Treatment of dysmenorrhea includes hormonal suppression of the menstrual cycle, and/or analgesics; more severe cases with strong pain and disability may require earlier surgical intervention to excise disease while preserving fertility desires.
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- 2022
36. The association between season, day length, and temperature on clinical outcomes after cryopreserved embryo transfer
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Katharine F.B. Correia, Leslie V. Farland, Stacey A. Missmer, and Catherine Racowsky
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Adult ,Cryopreservation ,Photoperiod ,Temperature ,Oocyte Retrieval ,Obstetrics and Gynecology ,Embryo Transfer ,Cohort Studies ,Reproductive Medicine ,Pregnancy ,Humans ,Female ,Seasons ,Live Birth ,Retrospective Studies - Abstract
To investigate whether there is an association between season, temperature, and day length at oocyte retrieval and/or embryo transfer (ET) and clinical outcomes in frozen ET cycles.Retrospective cohort study.Large academically affiliated research hospital.A total of 3,004 frozen ET cycles from 1,937 different women with oocyte retrieval and transfer between 2012 and 2017.None.Implantation, clinical pregnancy, spontaneous abortion, and live birth.Frozen ETs with oocyte retrieval dates in summer had 45% greater odds of clinical pregnancy (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.15-1.82) and 42% greater odds of live birth (OR, 1.42; 95% CI, 1.13-1.79) compared with those with oocyte retrieval dates in winter. A 41% greater odds of clinical pregnancy (OR, 1.41; 95% CI, 1.16-1.71) and 34% greater odds of live birth (OR, 1.34; 95% CI, 1.10-1.62) were observed among transfers with an average temperature at oocyte retrieval in the highest tertile (17.2-33.3 °C) compared with those in the lowest tertile (-17.2-6.7 °C). There were no consistent associations between clinical outcomes and day length at oocyte retrieval or between season, day length, or temperature at transfer of thawed embryos.Warmer temperatures at oocyte retrieval are associated with higher odds of clinical pregnancy and live birth among frozen ET cycles. The consistent associations seen with oocyte retrieval dates and the lack of associations observed with ET dates suggest that any seasonality effects on in vitro fertilization success are related to ovarian function and not uterine receptivity.
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- 2022
37. Genetics and genomics of endometriosis☆
- Author
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Linda C. Giudice, Richard O. Burney, Christian M. Becker, Stacey A. Missmer, Grant Montgomery, Nilufer Rahmioglu, Peter A.W. Rogers, and Krina Zondervan
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- 2023
38. Contributors
- Author
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Vimla Aggarwal, T.M. Barber, Christian M. Becker, Karanveer Bhangu, Mats Brännström, Carolyn J. Brown, Richard O. Burney, Antonio Capalbo, Wai-Yee Chan, Andy Chun Hang Chen, Chien-Wen Chen, Ming-Jer Chen, Zi-Jiang Chen, Ya-Ching Chou, Kwong Wai Choy, Hugh J. Clarke, Marcos Cordoba, Pernilla Dahm-Kähler, Mo-Yu Dai, Jessica Garcia de Paredes, Guo-Lian Ding, Zirui Dong, Jin Du, C. Eguizabal, Heather E. Fice, S. Franks, Qing-Qin Gao, Jessica Giordano, Linda C. Giudice, Jordan Gosnell, Ting Guo, Meade Haller, Tristan Hardy, Qilong He, L. Herrera, Ali Honaramooz, Cheng Huang, He-Feng Huang, Ghada Hussein, Sylvie Jaillard, Hai-Ping Jiang, Zi-Ru Jiang, Laura Kasak, Kazuhiro Kawamura, Ali Khatibi, Chaini Konwar, Maris Laan, Guan-Lin Lai, Jonathan LaMarre, Dolores J. Lamb, Yin Lau Lee, Yi-Xuan Lee, Brynn Levy, Xin-Yuan Li, Yao Li, Yu-Fei Li, Jinyue Liao, Ming Liu, Xiaodong Liu, Xin-Mei Liu, Y.M. Dennis Lo, Xinyi Ma, Yun-Yi Ma, M. Martin-Inaraja, Stacey A. Missmer, Kai Kei Miu, Grant Montgomery, N. Montserrat, Cynthia C. Morton, Maria Jose Navarro-Cobos, Robert J. Norman, Marisol O’Neill, Fanghong Ou, Yanli Pang, Maria S. Peñaherrera, Maurizio Poli, Jose M. Polo, Jie Qiao, Yingying Qin, Endah Rahmawati, Nilufer Rahmioglu, Bernard Robaire, Wendy P. Robinson, Alice P. Rogers, Peter A.W. Rogers, I. Romayor, Kristiina Rull, Victor A. Ruthig, Matthew A. Shanahan, Xuan Shao, Andrew H. Sinclair, Leanne Stalker, Kate Stanley, Melissa Stosic, Michael Strug, Hoi-Ching Suen, Jia Ping Tan, Jose M. Teixeira, Nannan Thirumavalavan, Jason C.H. Tsang, Allison Tscherner, Elena J. Tucker, Chii-Ruey Tzeng, Ignatia B. Van den Veyver, Margot van Riel, Joris R. Vermeesch, Liesbeth Vossaert, Wei Wang, Yan-Ling Wang, Zhangting Wang, Ronald Wapner, Nicholas Werry, Jeffrey T. White, Samantha L. Wilson, Jun Wu, Peng Xu, Liying Yan, Zhiqiang Yan, William Shu Biu Yeung, Stephanie C.Y. Yu, Peng Yuan, Victor Yuan, Fan Zhai, Shidou Zhao, Yue Zhao, Boryana Zhelyazkova, Qi Zhou, and Krina Zondervan
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- 2023
39. Menstrual cycle characteristics and incident cancer: a prospective cohort study
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Siwen Wang, Yi-Xin Wang, Helena Sandoval-Insausti, Leslie V Farland, Jan L Shifren, Dan Zhang, JoAnn E Manson, Brenda M Birmann, Walter C Willett, Edward L Giovannucci, Stacey A Missmer, and Jorge E Chavarro
- Subjects
Adult ,Male ,Adolescent ,Rehabilitation ,Obstetrics and Gynecology ,Original Articles ,Middle Aged ,Endometrial Neoplasms ,Reproductive Medicine ,Humans ,Female ,Obesity ,Prospective Studies ,Menstrual Cycle ,Retrospective Studies - Abstract
STUDY QUESTIONAre menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?SUMMARY ANSWERIrregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.WHAT IS KNOWN ALREADYLong 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, DURATIONProspective cohort study. Prospective follow-up of 78 943 women participating in the Nurses’ Health Study II between 1989 and 2015.PARTICIPANTS/MATERIALS, SETTING, METHODSWe 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 CHANCEWe 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 CAUTIONOur 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 FINDINGSWomen 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 INTERESTThis 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 NUMBERN/A.
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- 2021
40. Pathophysiology, diagnosis, and management of endometriosis
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Andrew W Horne and Stacey A Missmer
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Delayed Diagnosis ,Infertility ,Uterus ,Infant, Newborn ,Endometriosis ,Humans ,Pain ,Female ,General Medicine - Abstract
Endometriosis affects approximately 190 million women and people assigned female at birth worldwide. It is a chronic, inflammatory, gynecologic disease marked by the presence of endometrial-like tissue outside the uterus, which in many patients is associated with debilitating painful symptoms. Patients with endometriosis are also at greater risk of infertility, emergence of fatigue, multisite pain, and other comorbidities. Thus, endometriosis is best understood as a condition with variable presentation and effects at multiple life stages. A long diagnostic delay after symptom onset is common, and persistence and recurrence of symptoms despite treatment is common. This review discusses the potential genetic, hormonal, and immunologic factors that lead to endometriosis, with a focus on current diagnostic and management strategies for gynecologists, general practitioners, and clinicians specializing in conditions for which patients with endometriosis are at higher risk. It examines evidence supporting the different surgical, pharmacologic, and non-pharmacologic approaches to treating patients with endometriosis and presents an easy to adopt step-by-step management strategy. As endometriosis is a multisystem disease, patients with the condition should ideally be offered a personalized, multimodal, interdisciplinary treatment approach. A priority for future discovery is determining clinically informative sub-classifications of endometriosis that predict prognosis and enhance treatment prioritization.
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- 2022
41. Pelvic floor, abdominal and uterine tenderness in relation to pressure pain sensitivity among women with endometriosis and chronic pelvic pain
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Daniel J. Clauw, Christine B. Sieberg, Steven E. Harte, Sawsan As-Sanie, Stacey A. Missmer, Amy L. Shafrir, and Elena Martel
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Pain Threshold ,Treatment response ,Pressure pain ,Endometriosis ,Pelvic Pain ,Article ,medicine ,Humans ,Pelvic floor ,business.industry ,Pelvic pain ,Obstetrics and Gynecology ,Pelvic Floor ,medicine.disease ,Abdominal Pain ,body regions ,Tenderness ,Cross-Sectional Studies ,medicine.anatomical_structure ,Reproductive Medicine ,Anesthesia ,Female ,Chronic Pain ,medicine.symptom ,Abdominal wall pain ,business ,UTERINE TENDERNESS - Abstract
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).
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- 2021
42. Menstrual Cycle Regularity and Length Across the Reproductive Lifespan and Risk of Cardiovascular Disease
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Yi-Xin Wang, Jennifer J. Stuart, Janet W. Rich-Edwards, Stacey A. Missmer, Kathryn M. Rexrode, Leslie V. Farland, Kenneth J. Mukamal, Scott M. Nelson, Caren G. Solomon, Abigail Fraser, and Jorge E. Chavarro
- Subjects
Adult ,Adolescent ,Longevity ,Hypercholesterolemia ,General Medicine ,Middle Aged ,Cohort Studies ,Young Adult ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Risk Factors ,Hypertension ,Humans ,Female ,Prospective Studies ,Menstrual Cycle - Abstract
ImportanceMenstrual cycle characteristics may be associated with an increased risk of cardiovascular disease (CVD). However, existing studies are limited, and few have explored the mediating role of established CVD risk factors.ObjectiveTo explore the associations of menstrual cycle characteristics across the reproductive lifespan with the risk of CVD and to what extent these associations were mediated by hypercholesterolemia, chronic hypertension, and type 2 diabetes.Design, Setting, and ParticipantsThis cohort study prospectively followed Nurses’ Health Study II participants between 1993 and 2017 who reported menstrual cycle regularity and length for ages 14 to 17 years and 18 to 22 years at enrollment in 1989 and updated current cycle characteristics in 1993 (at ages 29 to 46 years). Data analysis was performed from October 1, 2019, to January 1, 2022.ExposuresMenstrual cycle regularity and length across the reproductive lifespan.Main Outcomes and MeasuresIncident CVD events of interest, including fatal and nonfatal coronary heart disease (CHD; myocardial infarction [MI] or coronary revascularization) and stroke.ResultsA total of 80 630 Nurses’ Health Study II participants were included in the analysis, with a mean (SD) age of 37.7 (4.6) years and body mass index of 25.1 (5.6) at baseline. Over 24 years of prospective follow-up, 1816 women developed their first CVD event. Multivariable Cox proportional hazards models showed that, compared with women reporting very regular cycles at the same ages, women who had irregular cycles or no periods at ages 14 to 17, 18 to 22, or 29 to 46 years had hazard ratios for CVD of 1.15 (95% CI, 0.99-1.34), 1.36 (95% CI, 1.06-1.75), and 1.40 (95% CI, 1.14-1.71), respectively. Similarly, compared with women reporting a cycle length of 26 to 31 days, women reporting a cycle length 40 days or more or a cycle too irregular to estimate from ages 18 to 22 or 29 to 46 years had hazard ratios for CVD of 1.44 (95% CI, 1.13-1.84) and 1.30 (95% CI, 1.09-1.57), respectively. Mediation analyses showed that subsequent development of hypercholesteremia, chronic hypertension, and type 2 diabetes only explained 5.4% to 13.5% of the observed associations.Conclusions and RelevanceIn this cohort study, both irregular and long menstrual cycles were associated with increased rates of CVD, which persisted even after accounting for subsequently established CVD risk factors.
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- 2022
43. Fruit and vegetable consumption, pesticide residue intake from consumption of fruits and vegetables, and risk of uterine fibroids
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Colette P. Davis, Nichole A. Garzia, Kara Cushing-Haugen, Kathryn L. Terry, Yu-Han Chiu, Helena Sandoval-Insausti, Jorge E. Chavarro, Stacey A. Missmer, and Holly R. Harris
- Subjects
Embryology ,Reproductive Medicine - Abstract
To examine the association between the consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk.Prospective cohort study. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).Not applicable.81,782 premenopausal participants from the Nurses' Health Study II cohort were followed from 1991-2009 for the fruits and vegetable analysis, and 49,927 participants were followed from 1999-2009 for the pesticide residue burden analysis. Diet was assessed every four years with a food frequency questionnaire. Fruits and vegetables were classified into high- or low-pesticide-residues using a validated method based on surveillance data from the U.S. Department of Agriculture.Not applicable MAIN OUTCOME MEASURE(S): Cases of ultrasound or hysterectomy-confirmed fibroids were identified from self-reports to validated questionnaires.From 1991-2009, 9,706 incident cases of ultrasound or hysterectomy-confirmed fibroids were reported, and 4,195 incident cases were identified from 1999-2009. No association was observed between total fruit and vegetable consumption and uterine fibroid risk. Participants who consumed the highest intake of total fruits (≥4/day) were 10% less likely to develop uterine fibroids compared to participants who consumed1/day (95% CI=0.80-1.01; pOur findings suggest that pesticide residues on fruits and vegetables are not associated with a higher risk of uterine fibroids. Further, our results suggest that intake of fruits may be associated with a lower risk of fibroids. Future research in this area should focus on dietary exposures across the life course as well as assessment of class-specific pesticides.
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- 2022
44. Association of early life physical and sexual abuse with premature mortality among female nurses: prospective cohort study
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Yi-Xin Wang, Yang Sun, Stacey A Missmer, Kathryn M Rexrode, Andrea L Roberts, Jorge E Chavarro, and Janet W Rich-Edwards
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General Medicine - Abstract
Objective To explore associations between early life physical and sexual abuse and subsequent risk of premature mortality (death before age 70 years). Design Prospective cohort study. Setting The Nurses’ Health Study II (2001-19). Participants 67 726 female nurses aged 37-54 years when completing a violence victimization questionnaire in 2001. Main outcome measures Hazard ratios and 95% confidence intervals for total and cause specific premature mortality by childhood or adolescent physical and sexual abuse, estimated by multivariable Cox proportional hazard models. Results 2410 premature deaths were identified over 18 years of follow-up. Nurses who experienced severe physical abuse or forced sexual activity in childhood and adolescence had a higher crude premature mortality rate than nurses without such abuse in childhood or adolescence (3.15 v 1.83 and 4.00 v 1.90 per 1000 person years, respectively). The corresponding age adjusted hazard ratios for premature deaths were 1.65 (95% confidence interval 1.45 to 1.87) and 2.04 (1.71 to 2.44), respectively, which were materially unchanged after further adjusting for personal characteristics and early life socioeconomic status (1.53, 1.35 to 1.74, and 1.80, 1.50 to 2.15, respectively). Cause specific analyses indicated that severe physical abuse was associated with a greater risk of mortality due to external causes of injury and poisoning (multivariable adjusted hazard ratio 2.81, 95% confidence interval 1.62 to 4.89), suicide (3.05, 1.41 to 6.60), and diseases of the digestive system (2.40, 1.01 to 5.68). Forced sexual activity as a child and adolescent was associated with greater risk of mortality due to cardiovascular disease (2.48, 1.37 to 4.46), external injury or poisoning (3.25, 1.53 to 6.91), suicide (4.30, 1.74 to 10.61), respiratory disease (3.74, 1.40 to 9.99), and diseases of the digestive system (4.83, 1.77 to 13.21). The association of sexual abuse with premature mortality was stronger among women who smoked or had higher levels of anxiety during adulthood. Smoking, low physical activity, anxiety, and depression each explained 3.9-22.4% of the association between early life abuse and premature mortality. Conclusion Early life physical and sexual abuse could be associated with a greater risk of adult premature mortality.
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- 2023
45. Method used to identify adenomyosis and potentially undiagnosed adenomyosis in a large, U.S. electronic health record database
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M. C. Doherty, Cheryl Enger, Andrea K. Chomistek, Stacey A. Missmer, Anita M Loughlin, Gally Reznor, and Stephanie E Chiuve
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Epidemiology ,medicine.medical_treatment ,Population ,Hysterectomy ,computer.software_genre ,Logistic regression ,Cohort Studies ,Electronic health record ,Prevalence ,Electronic Health Records ,Humans ,Medicine ,Pharmacology (medical) ,Adenomyosis ,Medical diagnosis ,education ,education.field_of_study ,Database ,business.industry ,medicine.disease ,Cohort ,Female ,Diagnosis code ,business ,computer - Abstract
Background The prevalence of adenomyosis is underestimated due to lack of a specific diagnostic code and diagnostic delays given most diagnoses occur at hysterectomy. Objectives To identify women with adenomyosis using indicators derived from natural language processing (NLP) of clinical notes in the Optum Electronic Health Record database (2014-2018), and to estimate the prevalence of potentially undiagnosed adenomyosis. Methods An NLP algorithm identified mentions of adenomyosis in clinical notes that were highly likely to represent a diagnosis. The anchor date was date of first affirmed adenomyosis mention; baseline characteristics were assessed in the 12 months prior to this date. Characteristics common to adenomyosis cases were used to select a suitable pool of women from the underlying population, among whom undiagnosed adenomyosis might exist. A random sample of this pool was selected to form the comparator cohort. Logistic regression was used to compare adenomyosis cases to comparators; the predictive probability (PP) of being an adenomyosis case was assessed. Comparators having a PP ≥ 0.1 were considered potentially undiagnosed adenomyosis and were used to calculate the prevalence of potentially undiagnosed adenomyosis in the underlying population. Results Among 11 456 347 women aged 18-55 years in the underlying population, 19 503 were adenomyosis cases. Among 332 583 comparators, 22 696 women were potentially undiagnosed adenomyosis cases. The prevalence of adenomyosis and potentially undiagnosed adenomyosis was 1.70 and 19.1 per 1000 women aged 18-55 years, respectively. Conclusions Considering potentially undiagnosed adenomyosis, the prevalence of adenomyosis may be 10x higher than prior estimates based on histologically confirmed adenomyosis cases only.
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- 2021
46. Development of a visual, patient-reported tool for assessing the multi-dimensional burden of endometriosis
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Ahmed M. Soliman, Stacey A. Missmer, Marc R. Laufer, Samantha Eichner, Katy Vincent, Sawsan As-Sanie, Frank F. Tu, Ally Murji, and Sarah J. Cross
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Infertility ,medicine.medical_specialty ,Consensus ,Endometriosis ,030204 cardiovascular system & hematology ,Pelvic Pain ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Patient Reported Outcome Measures ,030212 general & internal medicine ,Intensive care medicine ,Laparoscopy ,medicine.diagnostic_test ,business.industry ,Optimal treatment ,Pelvic pain ,Symptom burden ,General Medicine ,medicine.disease ,Multi dimensional ,Female ,medicine.symptom ,business ,Healthcare providers - Abstract
OBJECTIVE: Inadequate communication about endometriosis symptom burden between women and healthcare providers is a barrier for optimal treatment. This study describes the development of the EndoWheel, a patient-reported assessment tool that visualizes the multi-dimensional burden of endometriosis to facilitate patient-provider communication. METHODS: Assessment questions for the tool were developed using an iterative Delphi consensus process. A consensus phase included additional practitioners and specialists to broaden perspectives and select revised statements. Semi-structured qualitative interviews were conducted with 13 women with endometriosis to assess the scoring and content of the measures. RESULTS: Symptoms included in the tool were pelvic pain, vaginal bleeding, bowel/bladder symptoms, energy levels, fertility, impact on activities, emotional and sexual well-being, and self-perceived global health. Additional life impact areas included relationships, social and occupational activity, and self-perception. The 13 interviewees completed the tool in approximately 5-6 minutes (range 4.0-7.5 minutes). Most participants (92%) perceived that the tool would enable better patient-provider communication, including addressing symptoms and areas of impact not normally discussed during office visits. CONCLUSION: Similar to visual circular tools used in burden assessment of other chronic diseases, the tool may facilitate improved patient dialogue with providers around endometriosis treatment goals and options.
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- 2021
47. Deep phenotyping of women with endometriosis-associated pain and bladder pain syndrome: the TRiPP (Translational Research in Pelvic Pain) study protocol
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Lysia Demetriou, Lydia Coxon, Michal Krassowski, Nilufer Rahmioglu, Lars Arendt-Nielsen, Qasim Aziz, Christian M. Becker, Judy Birch, Franscisco Cruz, Anja Hoffman, Andrew W. Horne, Lone Hummelshoj, Stephen McMahon, Jane Meijlink, Esther Pogatzki-Zahn, Christine B. Sieberg, Irene Tracey, Rolf-Detlef Treede, Stacey A. Missmer, Krina T. Zondervan, Jens Nagel, and Katy Vincent
- Abstract
ObjectivesChronic pelvic pain is common, poorly understood, and many women suffer for years without proper diagnosis and effective treatment. The Translational Research in Pelvic Pain (TRiPP) project takes a phenotyping approach, with a particular focus on endometriosis-associated pain (EAP) and bladder pain syndrome (IC/BPS), to improve our fundamental understanding of chronic pelvic pain. We believe that reconceptualising these conditions in the context of the multisystem dysfunction known for other chronic pain conditions rather than as end-organ pathologies has the potential to improve our understanding of the conditions. Our approach combines clinical, biological, physiological and psychological data to establish perturbations in the functions of pain-relevant systems that are specific to EAP and IC/BPS, and those that overlap both conditions and chronic pelvic pain more generally and associated quantitative biomarker profiles.DiscussionWe believe that TRiPP’s novel methodological approach will produce clinical data to aid our understanding of pelvic pain and identify underlying pathways for the development of refined animal models and targeted therapeutic treatments.
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- 2022
48. Prevalence of chronic pelvic pain by sexual orientation in a large cohort of young women in the United States
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Ariella R. Tabaac, Cindy Chwa, Megan E. Sutter, Stacey A. Missmer, Elizabeth R. Boskey, S. Bryn Austin, Frances Grimstad, and Brittany M. Charlton
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Adult ,Male ,Urology ,Endocrinology, Diabetes and Metabolism ,Sexual Behavior ,Pelvic Pain ,Article ,United States ,Psychiatry and Mental health ,Sexual and Gender Minorities ,Young Adult ,Endocrinology ,Cross-Sectional Studies ,Reproductive Medicine ,Prevalence ,Quality of Life ,Bisexuality ,Humans ,Female ,Heterosexuality - Abstract
Background Sexual minority (lesbian, bisexual, mostly heterosexual) young women face many sexual and reproductive health disparities, but there is scant information on their experiences of chronic pelvic pain, including an absence of information on prevalence, treatment, and outcomes. Aim The purpose of this study was to describe the characteristics of chronic pelvic pain experiences of young women by sexual orientation identity and gender of sexual partners. Methods The analytical sample consisted of a nationwide sample of 6,150 U.S. young women (mean age = 23 years) from the Growing Up Today Study who completed cross-sectional questionnaires from 1996 to 2007. Outcomes Age-adjusted regression analyses were used to examine groups categorized by sexual orientation identity (completely heterosexual [ref.], mostly heterosexual, bisexual, lesbian) and gender of sexual partner (only men [ref.], no partners, both men, and women). We examined differences in lifetime and past-year chronic pelvic pain symptoms, diagnosis, treatment, and quality of life outcomes. Sensitivity analyses also examined the role of pelvic/gynecologic exam history and hormonal contraceptive use as potential effect modifiers. Results Around half of all women reported ever experiencing chronic pelvic pain, among whom nearly 90% had past-year chronic pelvic pain. Compared to completely heterosexual women, there was greater risk of lifetime chronic pelvic pain among mostly heterosexual (risk ratio [RR] = 1.30, 95% confidence interval [CI]: 1.22–1.38), bisexual (RR = 1.30, 95% CI: 1.10–1.52), and lesbian (RR = 1.23, 95% CI: 1.00–1.52) young women. Additionally, compared to young women with only past male sexual partners, young women who had both men and women as past sexual partners were more likely to report chronic pelvic pain interfered with their social activities (b = 0.63, 95% CI: 0.25–1.02), work/school (b = 0.55, 95% CI: 0.17–0.93), and sex (b = 0.53, 95% CI: 0.05–1.00). Clinical Implications Healthcare providers, medical education, and field-wide standards of care should be attentive to the way sexual orientation-based healthcare disparities can manifest into differential prognosis and quality of life outcomes for women with chronic pelvic pain (particularly bisexual women). Strengths & Limitations Our study is the first to examine a variety of chronic pelvic pain outcomes in a nationwide U.S. sample across different outcomes (ie, past-year and lifetime). Though limited by sample homogeneity in terms of age, race, ethnicity, and gender, findings from this article provide foundational insights about chronic pelvic pain experiences of sexual minority young women. Conclusion Our key finding is that sexual minority women were commonly affected by chronic pelvic pain, and bisexual women face pain-related quality of life disparities.
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- 2022
49. Optimizing the control group for evaluating ART outcomes: can outpatient claims data yield a better control group?
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Charles C. Coddington, Judy E. Stern, Chia ling Liu, Hafsatou Diop, Xiaohui Cui, Stacey A. Missmer, Leslie V. Farland, Dmitry Dukhovny, Daksha Gopal, Howard Cabral, and Sunah S. Hwang
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Adult ,Infertility ,medicine.medical_specialty ,Reproductive Techniques, Assisted ,media_common.quotation_subject ,medicine.medical_treatment ,Reproductive medicine ,Fertility ,infertile ,Birth certificate ,subfertile ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,030225 pediatrics ,Outpatients ,Genetics ,medicine ,Humans ,Assisted Reproduction Technologies ,Generalized estimating equation ,Genetics (clinical) ,media_common ,030219 obstetrics & reproductive medicine ,Assisted reproductive technology ,business.industry ,Obstetrics ,Infant, Newborn ,Obstetrics and Gynecology ,APCD ,General Medicine ,Infant, Low Birth Weight ,medicine.disease ,ART outcomes ,Control Groups ,Confidence interval ,Reproductive Medicine ,Relative risk ,Premature Birth ,Female ,business ,Infertility, Female ,Maternal Age ,Developmental Biology - Abstract
Purpose We previously developed a subfertile comparison group with which to compare outcomes of assisted reproductive technology (ART) treatment. In this study, we evaluated whether insurance claims data in the Massachusetts All Payers Claims Database (APCD) defined a more appropriate comparison group. Methods We used Massachusetts vital records of women who delivered between 2013 and 2017 on whom APCD data were available. ART deliveries were those linked to a national ART database. Deliveries were subfertile if fertility treatment was marked on the birth certificate, had prior hospitalization with ICD code for infertility, or prior fertility treatment. An infertile group included women with an APCD outpatient or inpatient ICD 9/10 infertility code prior to delivery. Fertile deliveries were none of the above. Demographics, health risks, and obstetric outcomes were compared among groups. Multivariable generalized estimating equations were used to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI). Results There were 70,726 fertile, 4,763 subfertile, 11,970 infertile, and 7,689 ART-treated deliveries. Only 3,297 deliveries were identified as both subfertile and infertile. Both subfertile and infertile were older, and had more education, chronic hypertension, and diabetes than the fertile group and less than the ART-treated group. Prematurity (aRR = 1.15–1.17) and birthweight (aRR = 1.10–1.21) were increased in all groups compared with the fertile group. Conclusion Although the APCD allowed identification of more women than the previously defined subfertile categorization and allowed us to remove previously unidentified infertile women from the fertile group, it is not clear that it offered a clinically significantly improved comparison group.
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- 2021
50. Validity of self-reported endometriosis: a comparison across four cohorts
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Julie R. Palmer, Marina Kvaskoff, Lauren A. Wise, Amy L. Shafrir, Kathryn L. Terry, Stacey A. Missmer, P. Vinayak, L. M. Katuska, and Z. O. Shuaib
- Subjects
medicine.medical_specialty ,media_common.quotation_subject ,Endometriosis ,Reproductive medicine ,Fertility ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,medicine ,Humans ,Risk factor ,Stage (cooking) ,Child ,media_common ,030219 obstetrics & reproductive medicine ,business.industry ,Medical record ,Rehabilitation ,Obstetrics and Gynecology ,Original Articles ,medicine.disease ,Reproductive Medicine ,030220 oncology & carcinogenesis ,Family medicine ,Cohort ,Female ,Self Report ,business ,Cohort study - Abstract
STUDY QUESTION How accurately do women report a diagnosis of endometriosis on self-administered questionnaires? SUMMARY ANSWER Based on the analysis of four international cohorts, women self-report endometriosis fairly accurately with a > 70% confirmation for clinical and surgical records. WHAT IS KNOWN ALREADY The study of complex diseases requires large, diverse population-based samples, and endometriosis is no exception. Due to the difficulty of obtaining medical records for a condition that may have been diagnosed years earlier and for which there is no standardized documentation, reliance on self-report is necessary. Only a few studies have assessed the validity of self-reported endometriosis compared with medical records, with the observed confirmation ranging from 32% to 89%. STUDY DESIGN, SIZE, DURATION We compared questionnaire-reported endometriosis with medical record notation among participants from the Black Women’s Health Study (BWHS; 1995-2013), Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale (E3N; 1990-2006), Growing Up Today Study (GUTS; 2005–2016), and Nurses’ Health Study II (NHSII; 1989–1993 first wave, 1995–2007 second wave). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants who had reported endometriosis on self-administered questionnaires gave permission to procure and review their clinical, surgical, and pathology medical records, yielding records for 827 women: 225 (BWHS), 168 (E3N), 85 (GUTS), 132 (NHSII first wave), and 217 (NHSII second wave). We abstracted diagnosis confirmation as well as American Fertility Society (AFS) or revised American Society of Reproductive Medicine (rASRM) stage and visualized macro-presentation (e.g. superficial peritoneal, deep endometriosis, endometrioma). For each cohort, we calculated clinical reference to endometriosis, and surgical- and pathologic-confirmation proportions. MAIN RESULTS AND THE ROLE OF CHANCE Confirmation was high—84% overall when combining clinical, surgical, and pathology records (ranging from 72% for BWHS to 95% for GUTS), suggesting that women accurately report if they are told by a physician that they have endometriosis. Among women with self-reported laparoscopic confirmation of their endometriosis diagnosis, confirmation of medical records was extremely high (97% overall, ranging from 95% for NHSII second wave to 100% for NHSII first wave). Importantly, only 42% of medical records included pathology reports, among which histologic confirmation ranged from 76% (GUTS) to 100% (NHSII first wave). Documentation of visualized endometriosis presentation was often absent, and details recorded were inconsistent. AFS or rASRM stage was documented in 44% of NHSII first wave, 13% of NHSII second wave, and 24% of GUTS surgical records. The presence/absence of deep endometriosis was rarely noted in the medical records. LIMITATIONS, REASONS FOR CAUTION Medical record abstraction was conducted separately by cohort-specific investigators, potentially introducing misclassification due to variation in abstraction protocols and interpretation. Additionally, information on the presence/absence of AFS/rASRM stage, deep endometriosis, and histologic findings were not available for all four cohort studies. WIDER IMPLICATIONS OF THE FINDINGS Variation in access to care and differences in disease phenotypes and risk factor distributions among patients with endometriosis necessitates the use of large, diverse population samples to subdivide patients for risk factor, treatment response and discovery of long-term outcomes. Women self-report endometriosis with reasonable accuracy (>70%) and with exceptional accuracy when women are restricted to those who report that their endometriosis had been confirmed by laparoscopic surgery (>94%). Thus, relying on self-reported endometriosis in order to use larger sample sizes of patients with endometriosis appears to be valid, particularly when self-report of laparoscopic confirmation is used as the case definition. However, the paucity of data on histologic findings, AFS/rASRM stage, and endometriosis phenotypic characteristics suggests that a universal requirement for harmonized clinical and surgical data documentation is needed if we hope to obtain the relevant details for subgrouping patients with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) This project was supported by Eunice Kennedy Shriver National Institute of Child Health and Development grants HD48544, HD52473, HD57210, and HD94842, National Cancer Institute grants CA50385, R01CA058420, UM1CA164974, and U01CA176726, and National Heart, Lung, and Blood Institute grant U01HL154386. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. AS, SM, and KT were additionally supported by the J. Willard and Alice S. Marriott Foundation. MK 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. Funders had no role in the study design, conduct of the study or data analysis, writing of the report, or decision to submit the article for publication. LA Wise has served as a fibroid consultant for AbbVie, Inc for the last three years and has received in-kind donations (e.g. home pregnancy tests) from Swiss Precision Diagnostics, Sandstone Diagnostics, Kindara.com, and FertilityFriend.com for the PRESTO cohort. SA Missmer serves as an advisory board member for AbbVie and a single working group service for Roche; neither are related to this study. No other authors have a conflict of interest to report. Funders had no role in the study design, conduct of the study or data analysis, writing of the report, or decision to submit the article for publication. TRIAL REGISTRATION NUMBER N/A.
- Published
- 2021
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