Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women.

PROBLEM: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune-mediated conditions and endometriosis among young women. METHOD OF STUDY: This cross-sectional analysis in the Women's Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders. RESULTS: Participants with any autoimmune and/or inflammatory condition had an increased odds of co-occurring endometriosis (OR: 1.87; CI: 0.92-3.80), as did participants with allergies (OR: 1.76; CI: 1.32-2.36), asthma (OR: 1.35; CI: 0.97-1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89-17.9), or previous mononucleosis (OR: 1.75; CI: 1.14-2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44-1.04). We observed a positive trend between the number of immune-mediated conditions and the odds of endometriosis (p-trend=0.0002). Endocrine disorders were not associated with endometriosis. CONCLUSIONS: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune-mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity.

Disparities in healthcare services in women with endometriosis with public vs private health insurance.

BACKGROUND: The goals of health disparities research are to identify facilitators and barriers to healthcare use to help eliminate health inequalities. There are few studies on disparities in healthcare access and use trends for patients with endometriosis that may lead to differences in appropriate care based on socioeconomic status. OBJECTIVE: This retrospective, cross-sectional study was conducted to compare health services use patterns and prevalence of co-morbidities of women with endometriosis with public (government-based) vs private (purchased or provided by employer) health insurance. STUDY DESIGN: A total of 342 deidentified datasets (171 randomly-selected cases per study group) from women with endometriosis 14-50 years old who were members of one health insurance company that provides both public and private health insurance coverage in Puerto Rico were analyzed. Patients were defined as having at least 1 endometriosis-related medical claim (ICD-9-617.xx; International Classification of Diseases, Ninth Revision, Clinical Modification) during the 3-year study period. RESULTS: Medical service (eg, hospital, laboratory, pathology, and radiology) use trends were 3 times lower in the public vs the private sector. Women in the public sector were 3.5 times less likely to have a laparoscopy, 2.7 times more likely to be prescribed opioid/narcotics, and were the only study subjects reporting emergency department use. Obstetrics and gynecology services were used >2-fold less by women in the public (29.5%) vs the private sector (70.5%) (P=.087). CONCLUSIONS: We report significant differences in the use trends of endometriosis-related medical services and prescriptions, indicating differences in healthcare access based on socioeconomic parameters. Our results support the development of public health programs to promote access to healthcare for patients with endometriosis irrespective of socioeconomic status and promote health disparity research in other healthcare systems.

Characteristics of women with endometriosis from the USA and Puerto Rico.

PURPOSE: To describe lifetime differences in clinical characteristics of women with endometriosis between the USA and Puerto Rico. METHODS: A descriptive study using self-administered demographic and clinical questionnaires was undertaken. Women with self-reported surgically diagnosed endometriosis who completed questionnaires from the Endometriosis Association (EA), Wisconsin, USA (n = 4358) and the Endometriosis Research Program (ERP) in Puerto Rico (n = 878), were included in this study. We compared demographic, gynecological and clinical history, frequency of endometriosis-associated symptoms and co-morbidities. RESULTS: Although both groups have similar symptomatology, EA respondents had significantly higher rates of chronic pelvic pain and incapacitating pain than ERP participants. EA respondents were significantly more likely to report a history of problems getting pregnant, heavy bleeding, and hysterectomy than ERP respondents. Miscarriages were more frequently reported by the ERP group. Co-morbidities such as allergies, chronic fatigue syndrome, and fibromyalgia were more prevalent in EA respondents, whereas asthma was significantly more frequent in participants from ERP. CONCLUSIONS: Overall, women with endometriosis from the USA and Puerto Rico reported high rates of pain and infertility and a similar spectrum of symptoms. Those from the EA reported longer time to diagnosis, and diagnostic delays than those from the ERP, which may explain the observed increased in rates of endometriosis-related symptoms and co-morbidities in EA as compared to ERP.

HDAC1 and HDAC2 are differentially expressed in endometriosis.

Epigenetic mechanisms have been ascribed important roles in endometriosis. Covalent histone modifications at lysine residues have been shown to regulate gene expression and thus contribute to pathological states in many diseases. In endometriosis, histone deacetylase inhibition (HDACi) resulted in reactivation of E-cadherin, attenuation of invasion, decreased proliferation of endometriotic cells, and caused lesion regression in an animal model. This study was conducted to assess basal and hormone-regulated gene expression levels of HDAC1 and HDAC2 (HDAC1/2) in cell lines and protein expression levels in tissues. Basal and steroid hormone-regulated HDAC1/2 gene expression levels were determined by quantitative polymerase chain reaction in cell lines and tissues. Protein levels were measured by immunohistochemistry (IHC) in tissues on an endometriosis tissue microarray (TMA). Basal HDAC1/2 gene expression levels were significantly higher in endometriotic versus endometrial stromal cells, which was confirmed by Western blot analysis. Estradiol (E2) and progesterone (P4) significantly downregulated HDAC1 expression in endometrial epithelial cells. Levels of HDAC2 were upregulated by E2 and downregulated by E2 + P4 in endometrial stromal cells. Hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed that HDAC1/2 proteins were expressed in a substantial proportion of lesions and endometrium from patients, and their expression levels varied according to lesion localization. The highest proportion of strong HDAC1 immunostaining was seen in ovarian, skin, and gastrointestinal lesions, and of HDAC2 in skin lesions and endometrium from patients with endometriosis. These studies suggest that endometriosis etiology may be partially explained by epigenetic regulation of gene expression due to dysregulations in the expression of HDACs.

Single-nucleotide polymorphisms in the lysyl oxidase-like protein 4 and complement component 3 genes are associated with increased risk for endometriosis and endometriosis-associated infertility.

This study was conducted to assess genetic associations with endometriosis in a Puerto Rican population. Statistically significant differences in the allelic frequencies and genotype distribution of genetic variants in lysyl oxidase-like protein 4 (LOXL4) and complement component 3 (C3) were documented in patients with endometriosis-associated infertility versus controls, and in patients with endometriosis versus controls, respectively. In women who have the risk genotype at both single-nucleotide polymorphisms, the estimated risk for endometriosis nearly doubled.

Quantification of the impact of endometriosis symptoms on health-related quality of life and work productivity.

OBJECTIVE: To quantify the impact of endometriosis-related symptoms on physical and mental health status, health-related quality of life, and work-related aspects (absenteeism, presenteeism, work productivity, and activity impairment). DESIGN: Cross-sectional quantitative study. SETTING: Academic and research institution. PATIENT(S): Women (n = 193) with self-reported surgically diagnosed endometriosis from the Endometriosis Patient Registry at Ponce School of Medicine and Health Sciences (PSMHS). INTERVENTION(S): Anonymous questionnaire divided into three sections consisting of questions from the Patient Health Survey (SF-12), the Endometriosis Health Profile (EHP-5), and the Work Productivity and Activity Impairment Survey (WPAI). MAIN OUTCOME MEASURE(S): Quantification of impact of endometriosis symptoms on physical and mental health status, health-related quality of life, absenteeism, presenteeism, work productivity, and activity impairment. RESULT(S): Patients had SF-12 scores denoting statistically significant disability in the physical and mental health components. They also reported an average of 7.41 hours (approximately one working day) of work time lost during the week when the symptoms are worse. In addition, the WPAI scores showed a high impact on work-related domains: 13% of average loss in work time (absenteeism), 65% of work impaired (presenteeism), 64% of loss in efficiency levels (work productivity loss), and 60% of daily activities perturbed (activity impairment). CONCLUSION(S): Endometriosis symptoms such as chronic, incapacitating pelvic pain and infertility negatively and substantially impact the physical and mental health status, health-related quality of life, and productivity at work of women.

Patients' report on how endometriosis affects health, work, and daily life.

The objective of this study was to assess the burden of endometriosis by obtaining patient-reported outcome data describing the experience of living with this disease. Survey data from 107 women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work, and daily life.

Self-reported prevalence of endometriosis and its symptoms among Puerto Rican women.

OBJECTIVE: To determine the prevalence of endometriosis and its symptoms in a Puerto Rican cohort, and to describe the menstrual, obstetric, and clinical profiles of the women. METHODS: A self-administered questionnaire was given to 1285 Puerto Rican women. Categorical variables were compared using chi2 analysis or Fisher exact test. RESULTS: There were 57 self-reported cases of endometriosis (48 surgically confirmed) among 1193 valid questionnaires, for a point prevalence of 4.0%. A diagnosis of endometriosis was significantly associated with dysmenorrhea, dyspareunia, and chronic pelvic pain, but not with menstrual cycle characteristics. Undiagnosed women commonly reported signs and symptoms of endometriosis. CONCLUSIONS: The estimated prevalence of endometriosis in Puerto Rico is 4.0%, comparable to what has been reported in other populations. Endometriosis symptoms were common in the population surveyed, indicating the need for increased awareness and development of public health policies leading to early diagnosis and appropriate management.