Endometriosis: a high-risk population for major chronic diseases?Marina Kvaskoff, Fan Mu, Kathryn L. Terry et al.|Human Reproduction Update|2015 BACKGROUND: Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS: We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS: We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS: Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If these relationships are confirmed, these findings may have important implications in screening practices and in the management and care of endometriosis patients.
Endometriosis and Risk of Coronary Heart DiseaseFan Mu, Janet W. Rich‐Edwards, Eric B. Rimm et al.|Circulation Cardiovascular Quality and Outcomes|2016 BACKGROUND: Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women's risk for coronary heart disease (CHD). METHODS AND RESULTS: We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses' Health Study II (1989-2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98), angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these CHD end points combined (1.62; 1.39-1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02-4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35-2.02; 50< age ≤55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis. CONCLUSIONS: In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD.
Association Between Endometriosis and Hypercholesterolemia or HypertensionAn altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years. Multivariable Cox proportional hazards models were applied. In 1989, there were 4244 women with laparoscopically confirmed endometriosis and 91 554 women without. After adjusting for demographic, anthropometric, family history, reproductive, dietary, and lifestyle risk factors prospectively, comparing women with laparoscopically confirmed endometriosis to women without, the relative risks were 1.25 (95% confidence interval, 1.21–1.30) for development of hypercholesterolemia and 1.14 (95% confidence interval, 1.09–1.18) for hypertension. Conversely, the relative risks of developing laparoscopically confirmed endometriosis were 1.22 (95% confidence interval, 1.15–1.31) comparing women with hypercholesterolemia to women without and 1.29 (95% confidence interval, 1.18–1.41) comparing women with hypertension to women without. The strength of associations of laparoscopically confirmed endometriosis with hypercholesterolemia or hypertension was strongest among women aged ≤40 and weakened as age increased ( P values for interaction <0.001). We observed that ≈45% of the associations between endometriosis and hypercholesterolemia and hypertension could be accounted for by treatment factors after endometriosis diagnosis, including greater frequency of hysterectomy/oophorectomy and earlier age for this surgery. In this large cohort study, laparoscopically confirmed endometriosis was prospectively associated with increased risk of hypercholesterolemia and hypertension. Conversely, hypercholesterolemia and hypertension were prospectively associated with higher risk of laparoscopically confirmed endometriosis.
Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses' Health Study IIHolly R. Harris, Karen H. Costenbader, Fan Mu et al.|Annals of the Rheumatic Diseases|2016 The long‐term direct and indirect economic burden among Parkinson's disease caregivers in the United StatesBACKGROUND: Parkinson's disease is a progressive, disabling neurodegenerative disorder associated with significant economic burden for patients and caregivers. The objective of this study was to compare the direct and indirect economic burden of Parkinson's patients' caregivers with demographically matched controls in the United States, in the 5 years after first diagnosis of Parkinson's disease. METHODS: Policyholders (18-64 years old) linked to a Parkinson's disease patient (≥2 diagnoses of Parkinson's disease; first diagnosis is the index date) from January 1, 1998 to March 31, 2014, were selected from a private-insurer claims database and categorized as Parkinson's caregivers. Eligible Parkinson's caregivers were matched 1:5 to policyholders with a non-Parkinson's dependent (controls). Multivariable regression adjusted for baseline characteristics estimated direct costs (all-cause insurer cost [medical and prescription] and comorbidity-related medical costs; patient out-of-pocket costs) and indirect costs (disability and medically related absenteeism costs). Income progression was also compared between cohorts. RESULTS: A total of 1211 eligible Parkinson's caregivers (mean age, 56 years; 54% female) were matched to 6055 controls. In adjusted analyses, Parkinson's caregivers incurred significantly higher year 1 total all-cause insurer costs ($8999 vs $7117) and medical costs ($7081 vs $5568) (both P < 0.01) and higher prescription costs (range for years 1-5, $2506-2573 vs $1405-$1687) and total out-of-pocket costs ($1259-1585 vs $902-$1192) in years 1-5 (all P < 0.01). Parkinson's caregivers had significantly higher adjusted indirect costs in years 1-3 (range for years 1-3, $2054-$2464 vs $1681-$1857; all P < 0.05) and higher cumulative income loss over 5 years ($5967 vs $2634 by year 5; P for interaction = 0.03). CONCLUSIONS: Parkinson's caregivers exhibited higher direct and indirect costs and greater income loss compared with matched controls. © 2018 International Parkinson and Movement Disorder Society © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.