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The objective of this study was to evaluate the utility and impact of the Painful Periods Screening Tool (PPST) to improve healthcare delivery for people with symptoms of pelvic pain. The design of this study was a survey study. After IRB approval, patients aged 18-55 years with self-reported pelvic, abdominal, or lower back pain before, during, or after menstrual periods were invited to participate in the study from September 2020 to June 2021. Participants filled out the PPST questionnaire on the day of their Johns Hopkins clinic visit and the follow-up questionnaire 1-14 days after the clinic visit. Demographics and duration of pain were assessed, and participants who completed the PPST questionnaire were sent a follow-up questionnaire to assess utility and impact of PPST. Of the 1352 patients who met study eligibility, 1000 participants responded to both questionnaires. Most subjects (82.9%; 95% CI: 80.4-85.2%) reported having severe pelvic/abdominal or lower back pain during menses. Nine hundred fifteen participants (91.5%; 95% CI: 89.6-93.2%) reported that if given regularly, the PPST would help women discuss their pain symptoms with their healthcare provider. Six hundred seventy-eight participants (67.8%; 95% CI: 64.8-70.7%) reported that the PPST helped them initiate a conversation about their symptoms. Seven hundred seven participants (70.7%; 95% CI: 67.8-73.5%) were more comfortable discussing symptoms of pelvic pain with their provider after filling out the PPST. These findings support the utility of PPST as an endometriosis screening tool and suggest that this tool facilitated communication between patients and providers about pain symptoms., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objectives: To examine women's perceptions of endometriosis-associated disease burden and its impact on life decisions and goal attainment., Design: An anonymous online survey was distributed in October 2018 through the social media network MyEndometriosisTeam.com., Participants: Women aged 19 years and older living in several English-speaking countries who self-identified as having endometriosis., Outcome Measures: Patients' perspectives on how endometriosis has affected their work, education, relationships, overall life decisions and attainment of goals. Subanalyses were performed for women who identified as 'less positive about the future' (LPAF) or had 'not reached their full potential' (NRFP) due to endometriosis., Results: 743 women completed the survey. Women reported high levels of pain when pain was at its worst (mean score, 8.9 on severity scale of 0 (no pain) to 10 (worst imaginable pain)) and most (56%, n=415) experienced pain daily. Women reported other negative experiences attributed to endometriosis, including emergency department visits (66%, n=485), multiple surgeries (55%, n=406) and prescription treatments for symptoms of endometriosis (72%, n=529). Women indicated that they believed endometriosis had a negative impact on their educational and professional achievements, social lives/relationships and overall physical health. Most women 'somewhat agreed'/'strongly agreed' that endometriosis caused them to lose time in life (81%, n=601), feel LPAF (80%, n=589) and feel they had NRFP (75%, n=556). Women who identified as LPAF or NRFP generally reported more negative experiences than those who were non-LPAF or non-NRFP., Conclusions: Women who completed this survey reported pain and negative experiences related to endometriosis that were perceived to negatively impact major life-course decisions and attainment of goals. Greater practitioner awareness of the impact that endometriosis has on a woman's life course and the importance of meaningful dialogue with patients may be important for improving long-term management of the disease and help identify women who are most vulnerable., Competing Interests: Competing interests: SAM is a consultant for AbbVie, Oratel Diagnostics and Celmatix and receives research support from the National Institutes of Health, Department of Defense and Marriott Family Foundations. FFT has received research support from NICHD-NIH and NIDDK-NIH, earns royalties from UpToDate, has served as a consultant for AbbVie, Myovant, and Uroshape, and conducts sponsored research for Eximis and Dot Laboratories. AMS, SCh, SCr, SE and OAF are employees of AbbVie and may own AbbVie stock/stock options. AH has received grant funding from the UK MRC, NIHR, CSO, Wellbeing of Women, Ferring, AstraZeneca, the Charles Wolfson Charitable Trust and Standard Life. His institution has received consultancy fees from Roche Diagnostics, Nordic Pharma, Ferring and AbbVie. He is Chair of the RCOG Academic Board, ESHRE National Representative for the UK, WES Board Member and Ambassador, SEUD Board Member, Trustee and Medical Advisor to Endometriosis UK and Medical Advisor to Pelvic Pain Support Network. BS is an employee of MyHealthTeams, which received compensation for the study and conducted the research on behalf of AbbVie. SA-S earns author royalties from UpToDate and has served as a consultant for AbbVie, Myovant and Eximis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We evaluated elagolix and leuprolide from the patient's perspective for the treatment of endometriosis-related pain., Area Covered: Preference weights from a published discrete choice experiment were used to evaluate preferences for treatment profiles simulating elagolix (150 mg/day and 200 mg/twice-daily dosages) and leuprolide for the treatment of moderate to severe endometriosis-related pain. Sensitivity analyses were conducted by varying the range of risk for pregnancy-related problems, moderate to severe hot flashes, and bone fracture across scenarios., Expert Opinion: The 200 mg twice daily dosage of elagolix is more likely to be preferred over leuprolide by patients with moderate to severe endometriosis-related pain in all scenarios explored in the evaluation and sensitivity analyses. The probability that an average respondent would select a treatment was sensitive to increases in risk of moderate to severe hot flashes for leuprolide and possible variations in the risk of pregnancy-related problems for both treatments but was not influenced by an increased risk of bone fracture., Conclusions: Patients' preferences for treatment of endometriosis-related pain should be evaluated using the benefits and risks of each pharmacological option. Respondents were more likely to prefer the treatment profile similar to 200 mg twice daily elagolix over that of leuprolide in all scenarios.

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 min (range 4.0-7.5 min). 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.

Study Objective: To determine the prevalence and pattern of opioid use in endometriosis and the characteristics of patients prescribed an opioid using medical insurance claims data., Design: We performed a retrospective cohort analysis of data from the Truven MarketScan Commercial database for the period of January 1, 2011 to December 31, 2016., Setting: The Truven database includes inpatient, outpatient, and prescription claims covering more than 115 million unique individuals and over 36 million inpatient hospital discharges across multiple payer types and all 50 states., Patients: Women with endometriosis were defined as those with 1 inpatient or 2 outpatient codes for endometriosis., Interventions: No interventions were assigned. Women who filled an opioid prescription within 12 months of diagnosis were placed in the opioid cohort and women who did not fill an opioid prescription were placed in the nonopioid cohort., Measurements and Main Results: Baseline characteristics were evaluated 12 months preindex (date of the first diagnosis) and opioid use was assessed for 12 months after the index date. The dataset included 58 472 women with endometriosis. Of these, 61.7% filled an opioid prescription during the study period. More than 95% filled prescriptions for short-acting opioids (SAOs) only, 4.1% filled prescriptions for both SAOs and extended-release/long-acting opioids (LAOs), and 0.6% filled prescriptions for LAOs only. Patients who filled an opioid prescription had higher baseline comorbidities (especially gynecologic and chronic pain comorbidities) and endometriosis-related medication use compared with patients who did not fill an opioid prescription during the study period. Patients who filled both LAO and SAO prescriptions had the highest total days' supply of opioids, the proportion of days covered by prescriptions, and morphine equivalent daily dose. These patients also had the highest proportions of opioid switching and dose augmentation. Statistical trends in data were not substantially altered when analyses excluded patients with chronic pain comorbidities or surgical opioid prescriptions., Conclusion: Although opioids are not a recommended treatment for endometriosis, more than half of our cohort filled an opioid prescription within 1 year after a first recorded diagnosis of endometriosis. Patients who filled an opioid prescription tended to use more endometriosis-related medications and have a higher comorbidity burden. Additional research is necessary to better understand the reasons and outcomes associated with opioid utilization in endometriosis and to determine if there is a more effective pain management treatment plan for patients taking opioids., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the utility, responsiveness, and thresholds for clinically meaningful change of a numerical rating scale for worst pain associated with dysmenorrhea (NRS-DYS) and nonmenstrual pelvic pain (NRS-NMPP) in women with moderate to severe endometriosis-associated pain., Design: Analysis of data from two phase III randomized clinical trials (EM-I [NCT01620528] and EM-II [NCT01931670])., Setting: Not applicable., Patient(s): Premenopausal women ages 18-49 years with moderate to severe endometriosis-associated pain., Intervention(s): Participants in both trials were randomized 3:2:2 to receive placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily for 6 months., Main Outcome Measure(s): NRS-DYS and NRS-NMPP., Result(s): EM-I enrolled 871 women and EM-II enrolled 815 women. For patients with a global impression of improvement at month 3, the least-squares mean change between baseline and month 3 was -3.6 (EM-I and EM-II) for NRS-DYS and -1.9 (EM-I) and -2.0 (EM-II) for NRS-NMPP. Standard errors of measurement were 2.99 (EM-I) and 2.86 (EM-II) for NRS-DYS and 1.74 (EM-I) and 1.71 (EM-II) for NRS-NMPP. Baseline half standard deviations were 0.78 (EM-I) and 0.85 (EM-II) for NRS-DYS and 0.92 (EM-I) and 0.96 (EM-II) for NRS-NMPP. Based on these results, clinically meaningful changes were defined as a reduction of 4 points for NRS-DYS and 2 points for NRS-NMPP., Conclusion(s): This study demonstrated the utility and responsiveness of separate numerical rating scales to assess worst pain for dysmenorrhea and NMPP in women with moderate to severe endometriosis-associated pain and identified initial thresholds for clinically meaningful change., (Copyright © 2020. Published by Elsevier Inc.)

Background: Women with endometriosis are commonly treated by their sole provider. In this single-provider model of care, women frequently report long diagnostic delays, unresolved pelvic pain, multiple laparoscopic surgeries, sequential consultations with numerous providers, and an overall dissatisfaction with care. The emergence of multidisciplinary endometriosis centers aims to reduce diagnostic delays, improve pain management, and promote patient satisfaction; however, baseline data at the time of presentation to a multidisciplinary center are lacking., Methods: A real-world, retrospective, single-site, cross-sectional study of women with surgically confirmed and/or clinically diagnosed endometriosis generated baseline data for a planned longitudinal assessment of multidisciplinary care of endometriosis. The primary objective was to determine the proportion of patients experiencing mild, moderate, or severe pain for dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia at entry into a multidisciplinary endometriosis clinic. Also explored were relationships between pain scores and clinical endpoints obtained from electronic medical records., Results: More than half (59%) of the study participants (n = 638) reported experiencing pelvic pain for ≥ 5 years. Pain intensity was highest for patients reporting dysmenorrhea, followed by NMPP, and dyspareunia. Significant correlations were observed between total pelvic pain and patient age (r = -0.22, p < 0.001, n = 506) and number of previous healthcare providers (r = 0.16, p = 0.006, n = 292); number of previous providers and duration of pain (r = 0.21, p = < 0.0001, n = 279); and duration of pain and years since diagnosis (r = 0.60, p < 0.001, n = 302). Mean pain scores differed significantly by age group for dysmenorrhea (p < 0.001), NMPP (p = 0.005), and total pelvic pain (p < 0.001), but not for dyspareunia (p = 0.06), with the highest mean pain scores reported among those < 30 years of age., Conclusion: These real-world data indicate that in the single-provider model of care, unresolved pelvic pain is common among women with endometriosis. Alternative care models, including a multidisciplinary approach, need to be evaluated for improvements in clinical outcomes. These data also highlight the importance of addressing NMPP, which may be particularly troublesome for patients.

Aim: To evaluate impact of co-morbidities on opioid use in endometriosis. Patients & m This was a retrospective analysis of data obtained from the Symphony Health database (July 2015-June 2018), which contains medical and pharmacy claims information on 79,947 women with endometriosis. Relative risk (RR) of postdiagnosis opioid use and supply duration associated with baseline co-morbidities were determined. ethods: Women with endometriosis using opioids at baseline were 61% more likely to receive opioids postdiagnosis (RR: 1.61; 95% CI: 1.59-1.63). Risk of prolonged opioid supply postdiagnosis was highest for those with prolonged supply at baseline (RR: 21.14; 20.14-22.19), and was 1.32 (1.26-1.38) for patients with ≥1 co-morbidity, 1.37 (1.31-1.43) for pain co-morbidities and 1.07 (1.04-1.11) for psychiatric co-morbidities. Results: Risk of opioid use after endometriosis diagnosis was greater in patients who used opioids before diagnosis. Risk of prolonged opioid use was greater if co-morbidities existed before diagnosis.Conclusion: Risk of opioid use after endometriosis diagnosis was greater in patients who used opioids before diagnosis. Risk of prolonged opioid use was greater if co-morbidities existed before diagnosis.

Selection of a personalized dose for an individual patient can be informed by the patient's preferences, translated as weights on each of the clinically relevant safety and efficacy drug attributes, based on results from a brief patient preference elicitation questionnaire. In this analysis, the weighted attributes were simulated to represent various endometriosis patient profiles. Exposure-response simulations were performed for elagolix, a drug approved for management of moderate to severe pain associated with endometriosis, across a range of plasma exposures corresponding to a range of doses. The results were combined to calculate a personalized clinical utility index. An interactive user-friendly online application was developed and envisioned as a physician's desk tool to personalize the dose selection process based on individual patient preferences. This demonstration should serve as an example of how patient/physician conversation can be facilitated with quantitative tools for personalizing the dose., (© 2020 AbbVie Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Objective: To evaluate fatigue burden and productivity impairments in Canadian women with a self-reported diagnosis of endometriosis (DxE)., Methods: From December 2018 to January 2019, Canadian women aged 18-49 years completed an online survey assessing fatigue via the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire. Fatigue T-scores were compared between women with and without a DxE, by age and endometriosis symptom severity, using t tests. Women with a DxE completed the Work Productivity and Activity Impairment - Specific Health Problem (WPAI-SHP) questionnaire. The effects of age and hallmark endometriosis symptoms on productivity impairments were assessed via analysis of variance., Results: Survey data included 2004 women with and 26 528 women without a DxE. Mean fatigue T-scores were 58.5 ± 10.1 in women with a DxE and 59.2 ± 10.1 in women with hallmark endometriosis symptoms (i.e., menstrual or non-menstrual pelvic pain/cramping, dyspareunia) versus 55.2 ± 9.4 in women without a DxE (both P < 0.001). Women with moderate or severe endometriosis symptoms had a mean T-score of 61.2 ± 9.4 versus 55.9 ± 10.1 for women with mild symptoms (P < 0.001). Women with moderate or severe hallmark endometriosis symptoms had mean T-scores of 59.6-62.9 versus 57.0-58.2 for women with mild or no symptoms (all comparisons P < 0.01). Women with a DxE reported 17.1% of work time missed, 41.8% impaired work ability, 46.5% overall work impairment, and 41.4% activity impairment per the WPAI-SHP. Women with a DxE aged 30-34 and 35-39 years consistently experienced the greatest effects of fatigue and productivity impairments., Conclusions: Canadian women with a DxE experience a substantial fatigue burden and significant productivity impairments., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dyspareunia experienced by women diagnosed with endometriosis is associated with a decreased health-related quality of life (HRQoL)., Aim: We evaluated the relationship of clinically meaningful improvements in dyspareunia with HRQoL changes among women with endometriosis., Methods: This was a post hoc analysis of pooled data from the phase III ELARIS-I and ELARIS-II clinical trials. Women aged 18-49 years with moderate to severe endometriosis-associated pain were randomized to placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. HRQoL was measured using the validated Endometriosis Health Profile-30 questionnaire (EHP-30), consisting of 5 core domains and a sexual intercourse modular domain. Dyspareunia was ranked 0-3 (none, mild, moderate, or severe) or not applicable using a daily eDiary and averaged monthly. A woman with a clinically meaningful dyspareunia response (dyspareunia responder) was defined as a woman with a reduction from the baseline in dyspareunia score greater than or equal to a predetermined cutoff while maintaining stable/decreased analgesic use., Outcomes: Dyspareunia response impact on EHP-30 scores was determined at 3 and 6 months using multivariate linear regression controlling for age, baseline EHP-30 scores, and dysmenorrhea and non-menstrual pelvic pain symptom severity., Results: Analysis included 1,368 women with a mean age of 32.2 years. Dyspareunia responders had significant improvements vs non-responders in all adjusted mean EHP-30 domain scores at months 3 and 6 (control and powerlessness: -17.8 and -18.5; emotional well-being: -10.0 and -10.4; pain: -15.3 and -15.7; self-image: -11.4 and -12.8; social support: -14.3 and -14.0; and sexual intercourse: -18.1 and -19.7; all P < .0001)., Clinical Implications: Dyspareunia improvements are associated with both personal and psychological benefits., Strengths & Limitations: This study involved a large sample of women from a well-defined patient population to provide statistical power in evaluating the results. As such, the findings may not be generalizable in a real-world setting. Although the perception of dyspareunia and its severity and the associated effect on HRQoL was subjective, the use of a large patient sample was used to minimize potential issues with this limitation., Conclusion: Clinically meaningful responses in dyspareunia are associated with improvements across multiple HRQoL domains among women with endometriosis. Agarwal SK, Soliman AM, Pokrzywinski RM, et al. Clinically Meaningful Reduction in Dyspareunia Is Associated with Significant Improvements in Health-Related Quality of Life Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials of Elagolix. J Sex Med 2020;17:2427-2433., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the health-related quality of life (HRQOL) of Canadian women with a self-reported diagnosis of endometriosis (DxE)., Methods: Canadian women aged 18-49 years completed a survey from December 2018 through January 2019 in which HRQOL was assessed via the 12-item Short Form Health Survey (SF-12) and Endometriosis Health Profile-30 (EHP-30) questionnaire. We used t tests to compare SF-12 scores between women with and without a self-reported DxE, as well as the severity of hallmark endometriosis symptoms, including menstrual pelvic pain/cramping, non-menstrual pelvic pain/cramping, and dyspareunia, for women with a DxE (moderate/severe vs. mild/none). The effects of overall endometriosis symptom severity on HRQOL were assessed via analysis of variance., Results: In total, 26 528 women without a DxE and 2004 women with a self-reported DxE were included. SF-12 scores were significantly lower for women with versus without a DxE (Mental Component Summary: 38.6 vs. 41.2; Physical Component Summary: 47.3 vs. 52.1; both P < 0.001), indicating reduced HRQOL. Moderate/severe hallmark endometriosis symptoms were associated with low SF-12 scores (i.e., worse HRQOL), with the greatest impact from non-menstrual pelvic pain/cramping. EHP-30 scores for women with a DxE ranged from 40.6 to 46.8, with the greatest impairment in self-image. Women with severe endometriosis symptoms had EHP-30 scores 1.3- and >2-fold higher (i.e., worse) than those with moderate and mild symptoms, at 67.5-74.6 versus 51.3-56.9 and 25.6-32.9, respectively., Conclusion: Canadian women with a self-reported diagnosis of endometriosis had significantly impaired health-related quality of life, which was inversely correlated with endometriosis symptom severity. This finding highlights a substantial unmet need among women with endometriosis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective : Endometriosis impacts health-related quality of life. The objective was to assess the validity and responsiveness of the Health-Related Productivity Questionnaire, version 2 (HRPQ). Methods : Outcome measures (Endometriosis Health Profile-30; pain scales; and global assessment) from Elaris Endometriosis I and II clinical trials (EM-I, EM-II) were used. Validity testing using Cohen's conventions was assessed. Known-groups validity was evaluated using generalized linear models comparing clinical responders, assessment of change, and the endometriosis impact. The effect size (ES) and standard error of means were calculated to evaluate responsiveness. Results : 871 and 815 women participated in the EM-I and EM-II trials. The total hours of lost work among employed women were 16.5 (±11.4) hours per week for EM-I and 15.2 (±11.3) for EM-II. The total hours of lost work among the household group were 8.3 (±8.7) hours for EM-I and 8.4 (±9.0) hours for EM-II. HRPQ discriminated between all known group assessments tested. Correlations for the HRPQ compared to other measures were small to moderate. Moderate to large ES was observed and the ability of the HRPQ to detect change was strong using patient-reported impressions. Conclusion : The HRPQ is a valid and responsive tool for evaluating patient-reported productivity at work and at home among women with endometriosis.

Objective: To evaluate the effects of elagolix on clinically meaningful improvements in health-related quality of life (HRQOL) measured by the EHP-30 (Endometriosis Health Profile-30)., Methods: Data from two phase III trials of elagolix for moderate to severe pain associated with endometriosis were pooled and analyzed as three groups: placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. Patients were administered the EHP-30 questionnaire at baseline, and at months 1, 3, and 6 of treatment. Previously established responder definitions were applied to determine percentages of patients with clinically meaningful EHP-30 improvements. The probability of meeting EHP-30 responder definitions with elagolix compared with placebo at months 3 and 6 was determined by Poisson regression analysis, controlling for baseline scores., Results: At month 6, the probabilities of meeting EHP-30 subscale responder definitions for pain, control and powerlessness, self-image, social support, emotional well-being, and sexual intercourse were 169% (adjusted relative risk [aRR]: 2.69, 95% CI 2.26-3.21), 129% (aRR 2.29, 95% CI 1.96-2.67), 80% (aRR 1.80, 95% CI 1.54-2.11), 70% (aRR 1.70, 95% CI 1.47-1.97), 67% (aRR 1.67, 95% CI 1.45-1.92), and 62% (aRR 1.62, 95% CI 1.36-1.92) greater, respectively (all P<.001), in the 200-mg group than in the placebo group. Although lower in magnitude than the 200-mg group, the 150-mg group also had greater probabilities of meeting responder definitions than the placebo group for all subscales except sexual intercourse. The probabilities of meeting responder definitions for pain, control and powerlessness, self-image, social support, and emotional well-being were 75% (aRR 1.75, 95% CI 1.44-2.14), 50% (aRR 1.50, 95% CI 1.25-1.80), 22% (aRR 1.22, 95% CI 1.01-1.47), 30% (aRR 1.30, 95% CI 1.09-1.53), and 35% (aRR 1.35, 95% CI 1.16-1.57) greater, respectively (all P<.05), in the 150-mg group than in the placebo group., Conclusion: Patients with moderate to severe pain associated with endometriosis and were treated with elagolix experienced clinically meaningful HRQOL improvements., Clinical Trial Registration: ClinicalTrials.gov, NCT01620528 and NCT01931670., Funding Source: AbbVie Inc.

Objective: This study sought to estimate the prevalence of diagnosis of endometriosis (DxE) in Canada and to assess the symptomatic and diagnostic experience of Canadian women with DxE., Method: A cross-sectional, online survey of women in Canada aged 18 to 49 was conducted from December 7, 2018 through January 24, 2019. Survey data were weighted by Canadian population statistics to estimate the prevalence, symptomatic burden, and diagnostic experience of DxE. Logistic regressions were used to assess differences in symptom burden between women with and without DxE., Results: The estimated prevalence of DxE was 7.0% (2004 women of 28 532 women surveyed). Almost half (47.5%) of women with DxE were aged 18 to 29 when they received an endometriosis diagnosis, and 84.1% experienced symptoms before diagnosis. More women with versus without DxE experienced menstrual pelvic pain or cramping (70.3% vs. 50.7%), non-menstrual pelvic pain or cramping (49.5% vs. 18.7%), dyspareunia (52.5% vs. 28.0%), and infertility (22.3% vs. 6.3%). Women with DxE were more likely to report severe menstrual pelvic pain or cramping (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.5-3.3), non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8-4.2), general abdominal pain (OR 3.0; 95% CI 2.5-3.6), and pelvic pressure (OR 3.0; 95% CI 2.3-3.8). Women with DxE reported an average 5.4-year diagnostic delay, with a 3.1-year delay from onset of symptoms to physician consultation and a 2.3-year delay between physician consultation and diagnosis., Conclusion: Self-reported DxE is prevalent among Canadian women and is associated with a substantial symptomatic burden. The 5.4-year diagnostic delay reported here indicates an important unmet need for more timely diagnosis of endometriosis in Canada., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: To compare all-cause and endometriosis-related healthcare resource utilization (HCRU) and healthcare costs by service categories (outpatient, inpatient, emergency room [ER], pharmacy) among patients with newly diagnosed endometriosis using opioids compared to patients with endometriosis not using opioids., Methods: A retrospective analysis of IBM® MarketScan® Commercial Claims data from 2009 to 2018 was performed for women aged 18-49 with newly diagnosed endometriosis (International Classification of Diseases (ICD)-9 code 617.xx; ICD-10 code N80.xx) over 24 months follow-up. Patients were stratified on the basis of opioid use within 12 months post first endometriosis diagnosis date. Patients with opioid use were 1:1 matched to patients without opioid use using propensity score matching., Results: A total of 85,329 female patients with a new endometriosis diagnosis were identified and 48,470 patients (24,235 opioid and 24,235 non-opioid users) remained after inclusion-exclusion criteria and matching. Opioid patients had an estimated mean 30.33 outpatient visits, 29.59 pharmacy fills, 0.28 inpatient visits, 0.65 ER visits, and total length of stay (LOS) was 1.01 days. Non-opioid patients had an estimated mean 27.94 outpatient visits, 22.06 pharmacy fills, 0.23 inpatient visits, 0.42 ER visits, and total LOS was 0.82 days. On average, opioid patients had significantly greater all-cause HCRU compared to non-opioid patients (all p < 0.0001). Among endometriosis-related healthcare utilization, there were similar ER visits, but lower outpatient visits, inpatient visits, and total LOS and higher pharmacy fills among opioid and non-opioid patients. Estimated mean all-cause costs were higher among opioid ($26,755) vs. non-opioid ($19,302) users (p < 0.0001). A similar trend was observed for estimated mean endometriosis-related costs., Conclusion: This analysis observed significantly higher all-cause HCRU and costs for opioid users compared to non-opioid users among patients with newly diagnosed endometriosis. While observed endometriosis-related costs were significantly higher in opioid users compared to non-opioid users during a 24-month follow-up period, endometriosis-related HCRU varied by service categories for these two populations over this time period.

Background: Endometriosis-related pain symptoms have a negative impact on health-related quality of life and productivity. In fact, as endometriosis-related symptom severity and the number of symptoms experienced increases, health-related quality of life decreases. Dysmenorrhea and nonmenstrual pelvic pain are prominent symptoms experienced by women with endometriosis and were shown to have improved with the oral, nonpeptide gonadotropin-releasing hormone antagonist, elagolix., Objective: The objective of this post hoc analysis was to address the question of if patients show a clinical response (in dysmenorrhea or nonmenstrual pelvic pain), do they also have improvements in health-related quality of life and in productivity?, Study Design: This post hoc analysis used data from the Elaris Endometriosis-I and Elaris Endometriosis-II phase III, randomized, placebo-controlled studies. A surgical diagnosis of endometriosis (in the past 10 years), premenopausal, aged 18-49 years, and moderate to severe endometriosis-associated pain were among the inclusion criteria for both trials. Women self-reported pain daily using a scale ranging from 0 (no pain) to 3 (severe pain); daily pain was assigned to either dysmenorrhea or nonmenstrual pelvic pain based on self-reported bleeding on that particular day. In addition, their self-reported endometriosis-associated pain must have been an average of moderate or severe during the month leading to baseline for inclusion in the trial program. Patients were characterized as achieving a clinical response for dysmenorrhea or nonmenstrual pelvic pain (ie, responder or nonresponder), which was defined as women who did not have an increase in analgesic use and who met the pain reduction score threshold at month 3. Pain reduction score thresholds were defined separately for dysmenorrhea and nonmenstrual pelvic pain in the trial using receiver-operating characteristics analysis. Health-related quality of life was assessed using the Endometriosis Health Profile-30; work productivity was assessed using the Health-Related Productivity Questionnaire., Results: Women enrolled in Elaris Endometriosis-I (n = 871) and Elaris Endometriosis-II (n = 815) were included in this analysis. Patients with a clinical response during treatment to dysmenorrhea or nonmenstrual pelvic pain also experienced a meaningful improvement in all domains of the Endometriosis Health Profile-30 at month 3. Patients who did not show a dysmenorrhea or nonmenstrual pelvic pain clinical response at month 3 did not exhibit mean improvements in Endometriosis Health Profile-30 domain scores that indicate an Endometriosis Health Profile-30 responder. Productivity improved among dysmenorrhea clinical responders. In the Elaris Endometriosis-I study, clinical responders lost a total of 5.9 hours compared with a total of 13.0 hours for nonresponders of employment-related work at month 3 (P < .0001). Among women in the Elaris Endometriosis-II study, a total of 4.1 hours and 10.4 employment-related hours were lost at month 3 for dysmenorrhea responders vs nonresponders (P < .001). Similar results were obtained when analyzed by non-enstrual pelvic pain responder status., Conclusion: Women with moderate to severe endometriosis-related pain, who are clinical responders based on dysmenorrhea and nonmenstrual pelvic pain, also experience significant and clinically meaningful improvement in health-related quality of life and productivity as measured by the Endometriosis Health Profile-30 and Health-Related Productivity Questionnaire, respectively., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: This retrospective cohort study evaluated the impact of endometriosis on the risks of work loss events and salary/growth over a 5-year period., Methods: Women aged 18-49 years with ≥ 1 endometriosis diagnosis were identified in a claims database and matched 1:1 to women without endometriosis (controls). The index date was the first endometriosis diagnosis date (endometriosis cohort) or a random date during the period of continuous eligibility (controls). Baseline characteristics were compared between cohorts descriptively. Average annual salaries were compared over the 5 years post-index using generalized estimating equations accounting for matching. Time-to-event analyses assessed risk of short-term disability, long-term disability, leave of absence, early retirement, and any event of leaving the workforce (Kaplan-Meier curves with log-rank tests)., Results: A total of 6851 matched pairs (mean age at index date: 38.7 years) were included in the salary growth analysis, with a subset of 1981 pairs in the risk of leaving the workforce analysis. In year 1, the endometriosis cohort had a lower average annual salary ($61,322) than controls ($64,720); salaries were lower in years 2-5 by $3697-$6600 (all p < 0.01). The endometriosis cohort experienced smaller salary growth than controls in all years, ranging from $438 vs. $1058 in year 1 to $4906 vs. $7074 in year 5 (all p < 0.05). In the Kaplan-Meier analyses, patients with endometriosis were significantly more likely than controls to leave the workforce for any reason, take a leave of absence, and use short-term disability (all log-rank tests p < 0.001). Additionally, the median number of years to each of these events was lower for the endometriosis cohort relative to the matched controls. Sensitivity analyses among patients with moderate-to-severe endometriosis and by salary brackets confirmed the primary analyses., Conclusions: Patients with endometriosis experienced lower annual salary and salary growth, as well as higher risks of work loss events, compared with matched controls.

Introduction: Endometriosis is a burdensome chronic condition for which conservative management is often recommended when indicated. Nonetheless, some women seek care for endometriosis in the emergency department (ED). We evaluated trends in ED visits for endometriosis from 2006 to 2015. Materials and Methods: Nationally representative estimates of ED visits for endometriosis by women aged 18-49 were extracted from the Health Care Utilization Project Nationwide Emergency Department Sample into three cohorts by calendar years 2006-2007, 2010-2011, and 2014-Q3 2015. Visits with a principal diagnosis code of endometriosis (International Classification of Disease, 9th Edition, Clinical Modification, code 617.x) were included. Patient and hospital characteristics were compared across cohorts using analysis of variance. Trends in the proportion of ED visits ending in inpatient admission and in mean charges (2015 USD) were assessed using generalized linear models controlling for patient and hospital characteristics. Results: The annual number of ED visits nationally was stable at ∼15,000 visits per year during 2006-2015. From 2006-2007 to 2014-2015, the composition of ED visits shifted away from private pay (42.0% vs. 35.3%) and uninsured (23.6% vs. 16.6%) to Medicaid (26.7% vs. 40.1%) and became more concentrated in metro-teaching hospitals (33.9% vs. 51.9%) ( p  < 0.001 for all). Inpatient admission rates declined from 20.1% to 9.2% ( p  < 0.001). Mean ED charges increased from $2458 to $4953 ( p  < 0.001). Conclusion: During 2006-2015, the number of ED visits for endometriosis remained stable, the inpatient admission/transfer rate declined by half, and mean charges per visit doubled.

Introduction: Endometriosis symptoms are nonspecific and overlap with other gynecologic and gastrointestinal diseases, leading to long diagnostic delays. The burden of endometriosis has been documented; however, little is known about the impact of diagnostic delays on healthcare costs leading up to diagnoses. The purpose of this study was to examine the economic impact of diagnostic delays on pre-diagnosis healthcare utilization and costs among patients with endometriosis., Methods: This was a retrospective database study of adult patients with a diagnosis of endometriosis from 1 January 2004 to 31 July 2016. Patients had continuous health plan enrollment 60 months prior to and 12 months following the earliest endometriosis diagnosis and ≥ 1 pre-diagnosis endometriosis symptom (dyspareunia, generalized pelvic pain, abdominal pain, dysmenorrhea, or infertility). Patients were assigned to short (≤ 1 year), intermediate (1-3 years), or long (3-5 years) delay cohorts based on the length of their diagnostic delay (time from first symptom to diagnosis). Healthcare resource utilization and costs were calculated and compared by cohort in the 60-month pre-diagnosis period., Results: A total of 11,793 patients were included in the study, of which 37.7% (4446/11,793), 27.0% (3179/11,793), and 35.3% (4168/11,793) had short, intermediate, and long delays, respectively. Patients with intermediate or long diagnostic delays had consistently more all-cause and endometriosis-related emergency visits and inpatient hospitalizations in the pre-diagnosis period than patients with short delays. Pre-diagnosis all-cause healthcare costs were significantly higher among patients with longer diagnostic delays, averaging $21,489, $30,030, and $34,460 among patients with a short, intermediate, and long delay, respectively (p < 0.001 for all pairwise comparisons). Endometriosis-related costs accounted for 12.5% ($3553/$28,376) of all-cause costs and followed a similar pattern., Conclusion: Patients with endometriosis who had longer diagnostic delays had more pre-diagnosis endometriosis-related symptoms and higher pre-diagnosis healthcare utilization and costs compared with patients who were diagnosed earlier after symptom onset, providing evidence in support of earlier diagnosis.

Objective: To evaluate the responsiveness of the Endometriosis Health Profile-30 (EHP-30) and ascertain score changes that are indicative of response to treatment. A post hoc analysis of two Phase III, double-blind, placebo-controlled, randomized clinical trials among women with moderate-to-severe endometriosis-associated pain (Elaris Endometriosis I and II [EM-I and EM-II]). Materials and Methods: EHP-30 core items and sexual relationship module were administered at day 1, month 3 (M3), and month 6 (M6) to monitor patient-reported impacts of endometriosis-related pain. A seven-response level Patient Global Impression of Change (PGIC) was administered at M3 and M6. Dysmenorrhea (DYS), nonmenstrual pelvic pain (NMPP), and dyspareunia (DYSP) were collected using a daily diary. Three psychometric approaches, "triangulation," were used to suggest responder thresholds for the EHP-30 domains. The three approaches were anchor- and distribution-based analyses and use of clinically relevant indicators (DYS, NMPP, DYSP). Results: EM-I and EM-II enrolled 871 and 815 women, respectively. All EHP-30 domains improved during the trials (M3, M6). Differences ( p  < 0.001) for all EHP-30 domains were found among the PGIC responses at M3 and M6, indicating greater change was associated with greater EHP-30 improvements. Large effect sizes were noted for all EHP-30 domains (EM-I range -0.59 to -1.80; EM-II range -0.52 to -1.59). EHP-30 thresholds of meaningful change ranged from -20 to -35, with greater changes indicating greater improvement in health status. Conclusion: Responder thresholds by EHP-30 domain are recommended to evaluate treatment efficacy. Clinicians can individualize goals of treatment by EHP-30 domain and track changes using the EHP-30.

Objectives: Evaluate all-cause and endometriosis-related health care resource utilization and costs among newly diagnosed endometriosis patients with high-risk versus low-risk opioid use or patients with chronic versus non-chronic opioid use., Methods: A retrospective analysis of IBM MarketScan ® Commercial Claims data from 2009 to 2018 was performed for females aged 18 to 49 with newly diagnosed endometriosis (International Classification of Diseases, Ninth Edition code: 617.xx; International Classification of Diseases, Tenth Edition code: N80.xx). Two sub-cohorts were identified: high-risk (⩾1 day with ⩾90 morphine milligram equivalents per day or ⩾1-day concomitant benzodiazepine use) or chronic opioid utilization (⩾90-day supply prescribed or ⩾10 opioid prescriptions). High-risk or chronic utilization was evaluated during the 12-month assessment period after the index date. Index date was the first opioid prescription within 12 months following endometriosis diagnosis. All outcomes were assessed over 12-month post-assessment period while adjusting for demographic and clinical characteristics., Results: Out of 61,019 patients identified, 18,239 had high-risk opioid use and 5001 chronic opioid use. Health care resource utilization drivers were outpatient visits and pharmacy fills, which were higher among high-risk versus low-risk patients (outpatient visits: 17.49 vs 15.51; pharmacy fills: 19.58 vs 16.88, p < 0.0001). Chronic opioid users had a higher number of outpatient visits (19.53 vs 15.00, p < 0.0001) and pharmacy fills (23.18 vs 16.43, p < 0.0001) compared to non-chronic opioid users. High-risk opioid users had significantly higher all-cause health care costs compared to low-risk opioid users (US$16,377 vs US$13,153; p < 0.0001). Chronic opioid users also had significantly higher all-cause health care costs compared to non-chronic opioid users (US$20,930 vs US$12,272; p < 0.0001). Similar patterns were observed among endometriosis-related HCRU, except pharmacy fills among high-risk and chronic sub-cohorts., Conclusion: This analysis demonstrates significantly higher all-cause and endometriosis-related health care resource utilization and total costs for high-risk opioid users compared to low-risk opioid users among newly diagnosed endometriosis patients over 1 year. Similar trends were observed for comparing chronic opioid users with non-chronic opioid users, except for endometriosis-related pharmacy fills and associated costs.

Background: Endometriosis profoundly impairs women's workplace and household productivity., Objective: The aim of this study was to evaluate the impact of elagolix on endometriosis-related workplace and household productivity losses., Methods: Data were pooled from two phase III trials of women aged 18-49 years with moderate to severe endometriosis-associated pain treated for 6 months with elagolix 150 mg daily (QD), 200 mg twice daily (BID), or placebo. The Health-Related Productivity Questionnaire was administered at baseline, Month 3, and Month 6 to determine workplace and household absenteeism and presenteeism. Productivity changes from baseline were compared between placebo and elagolix doses via analysis of covariance., Results: Workplace analyses included 1270 employed women and household analyses included 1565 women. At baseline, women reported average weekly losses of 16 workplace hours, 8.3 household work hours, 45% of scheduled work, and 64% of planned household chores. At Month 6, treatment with elagolix 150 mg QD or 200 mg BID increased productive workplace hours by 1.7 (95% CI 0.1-3.4; p = 0.041) and 5.4 h (95% CI 3.7-7.1; p < 0.001) relative to placebo, corresponding to gains of 5.2% (95% CI 0.7-9.7; p = 0.022) and 14.6% (95% CI 10.0-19.1; p < 0.001) of scheduled work, respectively. Both elagolix doses improved household productivity at Month 6 by 1.7 (95% CI 0.7-2.7) and 3.1 (95% CI 2.1-4.0) hours relative to placebo (both p < 0.001), with increases of 8.8% (95% CI 3.5-14.1; p = 0.001) and 20.4% (95% CI 15.1-25.6; p < 0.001) of planned household work., Conclusions: Treatment with elagolix improved endometriosis-related workplace and household productivity impairments., Trial Registration: ELARIS EM-I (NCT01620528) and ELARIS EM-II (NCT01931670).

Introduction: Despite guidance towards minimally invasive, outpatient procedures for endometriosis, many patients nonetheless receive inpatient care. Our objective was to assess trends in patient and hospital characteristics, surgical complications and hospital charges for women with an endometriosis-related inpatient admission in the United States., Methods: We conducted a pooled cross-sectional analysis of Healthcare Cost and Utilization Project Nationwide Inpatient Sample data. Visits were stratified into three time-period-defined cohorts (2006-2007, 2010-2011, and 2014 through the first three quarters of 2015). Visits were included if the patient was aged 18-49 years and the primary diagnosis code was for endometriosis (International Classification of Diseases, 9th Revision code 617.xx). We evaluated counts of inpatient admissions and rates of patient and hospital characteristics., Results: The number of inpatient admissions with a primary diagnosis code for endometriosis decreased by 72.8% from 2006 to 2015. At the same time, among those admitted for inpatient care for endometriosis, the proportions who had Medicaid insurance and multiple documented comorbidities increased. From 2006 to 2015, mean total hospital charges increased by 75% to $39,662 in 2015 US dollars, although average length of stay increased by <1 day., Conclusions: The number of inpatient admissions with a primary diagnosis of endometriosis decreased over the past decade, while surgical complications and associated hospital charges increased. The share of patients with multiple comorbidities increased and an increasing proportion of inpatient endometriosis admissions were covered by Medicaid and occurred at urban teaching hospitals. These findings suggest a demographic shift in patients receiving inpatient care for endometriosis towards more complex, vulnerable patients., Competing Interests: This study was funded by AbbVie, Inc., a commercial pharmaceutical company that manufactures a medication to treat endometriosis (URL: https://www.abbvie.com/). AbbVie participated in study design, data analysis, interpretation and review of results, preparation of the manuscript, and decision to publish. The development of this study and manuscript followed the Principles of Good Publication Practice (GPP3) for Company-Sponsored Medical Research. AS and KG are employees of AbbVie and may hold AbbVie stocks or stock options. AE and JB are employees of Medicus Economics, which received a research contract from AbbVie to conduct this research. SE and SM have served as research consultants for AbbVie. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To estimate the impact of elagolix on work loss due to endometriosis-associated pain., Design: Post hoc analysis of data from the Elaris I and II clinical trials., Setting: Not applicable., Patient(s): Employed women ages 18-49 years with moderate-to-severe endometriosis-associated pain., Intervention(s): In the two trials, participants were randomized to 6 months of treatment with placebo, elagolix 150 mg once a day, or elagolix 200 mg twice a day., Main Outcome Measure(s): Data on planned work hours, presenteeism, absenteeism, and total work loss (absenteeism + presenteeism) at baseline and month 3 were collected using the Health-Related Productivity Questionnaire., Result(s): This analysis included employed participants from EM-I (n = 672) and EM-II (n = 626). Between baseline and month 3, compared with participants treated with placebo, participants treated with elagolix 150 mg once a day gained > 2 hours total work/week (EM-I, 2.20 ± 1.03; EM-II, 2.65 ± 1.14). Participants treated with 200 mg twice a day gained > 4 hours total work/week (EM-I, 4.91 ± 1.04; EM-II, 4.64 ± 1.14). Both absenteeism and presenteeism were reduced, although most of the gain was due to reduced presenteeism. Estimated cost savings after 6 months of treatment with elagolix were > $1,500 U.S. at 150 mg once a day and > $3,300 U.S. at 200 mg twice a day., Conclusion(s): Compared with placebo, treating moderate-to-severe endometriosis-associated pain with elagolix reduced absenteeism and improved productivity in employed women, which should result in cost savings., Clinical Trial Number(s): NCT01620528 (EM-I) and NCT01931670 (EM-II)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of elagolix, an oral GnRH antagonist, for the reduction of fatigue in women with moderate or severe endometriosis-associated pain., Design: Randomized, double-blind, multicenter, placebo-controlled phase III trial., Setting: Clinics., Patient(s): A total of 860 women treated with elagolix or placebo., Intervention(s): Women received either elagolix at 150 mg daily (QD) orally, elagolix at 200 mg twice daily (BID) orally, or placebo., Main Outcome Measure(s): Change from baseline to month 1, 3, and 6 visits, in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire T-scores., Results(s): At baseline, 54%-74% of women with moderate to severe pain associated with endometriosis reported having fatigue-related issues "quite a bit" or "very much," depending on the question asked. Fatigue extent was reduced to 29%-43% and 14%-29% for women treated with elagolix at 150 mg QD and 200 mg BID, respectively, at 6 months, compared with 35%-50% with placebo. The resultant decrease in fatigue T-scores was significant after elagolix treatment compared with placebo at 6 months, with changes of -2.21 and -5.90 with elagolix at 150 mg QD and 200 mg BID, respectively. Significant reduction in fatigue scores were observed among patients reporting clinically meaningful response "reduction" in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia (-7.31, -6.62, and -4.31, respectively) compared with nonresponders., Conclusion(s): In women with moderate to severe endometriosis related pain, elagolix significantly reduces fatigue levels., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To quantify patient preferences for endometriosis-associated pain treatments and risk tolerance in exchange for pain reduction and to explore whether preferences vary on the basis of patient characteristics., Methods: US women with a self-reported physician diagnosis of endometriosis and moderate to severe dysmenorrhea and nonmenstrual pelvic pain (NMPP) completed an online discrete choice experiment survey. Each choice question had a pair of hypothetical treatments characterized by attributes with varying levels: improvements in severe dysmenorrhea, severe NMPP, and severe dyspareunia; mode of administration; and treatment-related risks of pregnancy-related problems, bone fracture later in life, and moderate to severe hot flashes. A random-parameters logit model was used to quantify preferences and the attributes' conditional relative importance., Results: A total of 250 women (mean age 34 years) completed the survey. The conditional relative importance of attributes was 3.66 for risk of moderate to severe hot flashes among respondents with and 3.58 among respondents without experience with moderate to severe hot flashes; 1.70, 1.49, and 1.48 for improvements in dyspareunia, NMPP, and dysmenorrhea, respectively; 0.60 for risk of pregnancy-related problems; 0.53 for mode of administration; and 0.49 for bone fracture risk. Preference weights for bone fracture risk levels were not statistically significantly different. In exchange for a greater improvement in dysmenorrhea from severe to mild (vs moderate), respondents without a history of hot flashes accepted a greater increase in the risk of moderate to severe hot flashes (38%) than did respondents with this history (16%)., Conclusions: Respondents placed the greatest weight on risk of hot flashes, followed by improvements in dyspareunia, NMPP, dysmenorrhea. Bone fracture risk did not drive preferences., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: To examine opioid use, opioid prescribing patterns, and timing of the first opioid prescription in endometriosis patients compared with matched women in the control group without endometriosis., Methods: We conducted a retrospective analysis of the Clinformatics Datamart database. Women diagnosed with endometriosis from January 2006 through December 2016 and aged 18-49 years were compared with women in the control group matched on age, region, race, insurance payer, and plan type. Key outcomes included: filled prescription for an opioid, multiple opioid prescriptions, number of days' supply, daily dose (morphine milligram equivalents), and concomitant opioid and benzodiazepine prescriptions. Cohorts were descriptively analyzed using t- and χ statistics and multivariable regression analyses yielded adjusted relative risk (RR) ratios and 95% CI., Results: The study sample included 53,847 endometriosis patients and 107,694 patients in the control group. The mean age was 38 years, 62.4% of patients were white, and 51.6% lived in the South. Women in the endometriosis case group, compared with women in the control group, were more likely to fill an opioid prescription (42,705 [79.3%] women in the case group vs 26,106 [24.2%] women in the control group; adjusted RR ratio 2.91; 2.87-2.94), had higher likelihood of filling prescriptions with a dose of 50 morphine milligram equivalents or more (24,544 [45.6%] vs 10,463 [9.7%]; adjusted RR ratio 4.07; 3.98-4.16) or 100 morphine milligram equivalents or more (8,013 [14.9%] vs 3,582 [3.3%]; adjusted RR ratio 3.56; 3.43-3.70). Women in the case group were more likely to have concomitant opioid and benzodiazepine prescriptions (5,453 [10.1%] vs 3,711 [3.5%]; adjusted RR ratio 1.95; 1.88-2.03) and to have used these drugs concurrently for at least 30 days (1,596 [3.0%] vs 1,265 [1.2%]; adjusted RR ratio 1.43; 1.34-1.52) or at least 90 days (875 [1.6%] vs 777 [0.7%]; adjusted RR ratio 1.27; 1.17-1.37). Similar results were obtained after excluding opioid prescriptions received during a 30-day postsurgery window., Conclusion: Women with endometriosis had higher probabilities of prolonged use of opioids and concomitant use with benzodiazepines compared with women without this condition., Funding Source: This study was funded by AbbVie, Inc.

Background: Endometriosis is a painful chronic inflammatory disease caused by endometrial tissue implanting and growing outside the uterus, resulting in pelvic pain symptoms and subfertility. Treatment imposes a substantial economic burden on the patient and health care system., Objective: To evaluate direct health care utilization and costs among women newly diagnosed with endometriosis compared with age-matched controls in a U.S. Medicaid population., Methods: This retrospective cohort study used deidentified health care claims from the 2007-2015 MarketScan Multi-State Medicaid Database. Women (aged 18-49 years) newly diagnosed with endometriosis (ICD-9-CM 617.xx) during January 2008 through September 2014 were identified (date of first diagnosis = index date). Age-matched women without endometriosis (controls) were selected from the database and assigned index dates matching the distribution for endometriosis patients. Direct health care resource utilization (HCRU) and costs (medical and pharmacy) over the 12-month post-index period (2015 U.S. dollars) were computed by service category (hospitalization, emergency room visits, outpatient services, and prescriptions) and compared between study cohorts using the chi-square test for proportions and t-test for continuous variables., Results: The final sample included 15,615 endometriosis patients and 86,829 matched controls. HCRU during the 12-month post-index follow-up period was significantly higher for endometriosis cases compared with controls in all measured categories. Hospital admissions occurred among 33.1% of cases and 7.2% of controls, and 65.8% of endometriosis patients were admitted for endometriosis-related surgery. Emergency room visits occurred in 71.5% of cases, and 42.2% of controls. Mean (SD) office visits were 10.4 (8.5) for endometriosis patients and 5.1 (6.9) for controls. Endometriosis patients had significantly more prescription claims than controls, 45.9 (42.0) versus 25.1 (39.1). Mean total direct health care costs were $13,670 ($29,843) for cases versus $5,779 ($23,614) for controls. All differences between cases and controls were significant at P < 0.001., Conclusions: Health care costs and resource utilization in all measured categories were higher among endometriosis cases than controls. The economic burden of endometriosis among patients with Medicaid insurance is substantial, underscoring the unmet medical need for earlier diagnosis and cost-effective treatments., Disclosures: This study was funded by AbbVie and conducted by Truven Health Analytics, an IBM Company. AbbVie participated in developing the study design, data analysis and interpretation, manuscript writing and revisions, and approval for publication. Soliman and Vora are employees of AbbVie and may own AbbVie stock/stock options. Surrey has served in a consulting role on research to AbbVie and is on the speaker bureau for Ferring Laboratories. Bonafede and Nelson are employees of Truven Health Analytics, an IBM Company, which received compensation from AbbVie for the overall conduct of the study and preparation of the manuscript. Agarwal has served in a consulting role on research to AbbVie. Preliminary results of this study were previously presented in a podium session at the 2017 American Society for Reproductive Medicine Scientific Congress and Expo; October 28-November 1, 2017; San Antonio, TX.

Aim: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain., Methods: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature., Results: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive., Conclusion: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Daily diary-based dysmenorrhea and nonmenstrual pelvic pain impact items were developed and validated to measure efficacy in endometriosis clinical trial settings. Items were developed across 3 stages of qualitative research, and their psychometric properties were explored in a phase II randomized controlled trial. Eight focus groups, 20 semistructured telephone interviews, and 15 face-to-face concept elicitation and cognitive debriefing interviews constituted the qualitative phase of the research. Psychometric properties of reliability, convergent validity, and responsiveness of the dysmenorrhea and nonmenstrual pelvic pain daily items were examined quantitatively in a phase II clinical trial of an investigational endometriosis treatment. Both qualitative concept elicitation and cognitive debriefing research yielded wording for item response options that resonated with adult women with endometriosis. Daily assessment of dysmenorrhea and nonmenstrual pelvic pain impact was the preferred measurement approach among adult women with endometriosis. Quantitatively, correlations between the dysmenorrhea and nonmenstrual pelvic pain items and other measures of pain impact provided endorsement for the items' convergent validity. Longitudinal measurement properties, involving test-retest reliability and sensitivity to change/responsiveness, offered evidence for the adequacy of the measurement properties of the daily diary-based dysmenorrhea and nonmenstrual pelvic pain impact items. Data from a phase II trial provided evidence that the daily dysmenorrhea and nonmenstrual pelvic pain impact items, developed and tested through qualitative research involving both focus groups and individual interviews, are well-defined, reliable, valid, and responsive for measuring the impact of pain in endometriosis to assess therapeutic response.

Objectives: Diagnostic delay is common in endometriosis. There is an unmet need for a symptom-based, patient-completed screening tool to facilitate discussions between patients and physicians about potential endometriosis symptoms. The objective of this study was to develop and assess the patient-completed Painful Periods Screening Tool (PPST) to assess the presence of potential endometriosis symptoms., Methods: To develop and refine the PPST, a cross-sectional qualitative study was conducted with women with endometriosis and healthy controls. Following identification of potentially relevant concepts in the literature and input from clinical experts, a draft version of the PPST was tested during in-depth individual interviews with 16 women: 11 with endometriosis and 5 healthy controls., Results: The six draft items of the PPST were refined iteratively in two rounds of interviews, and one item was deleted following the second set of interviews. All concepts included in the final five-item PPST were found to be relevant to women with endometriosis, and all 11 participants with endometriosis endorsed at least one of the items. No core symptoms of endometriosis were noted as missing from the PPST., Conclusion: The PPST assesses the most important endometriosis-related symptoms and may help facilitate discussions between patients and physicians, promoting earlier diagnosis and treatment of endometriosis.

Background: Endometriosis has been associated with higher rates of various chronic conditions, but its epidemiological data are fragmented and dated. We sought to compare the incidence of developing commonly occurring comorbidities among patients with and without endometriosis in a large, contemporary patient cohort that reflects real-world clinical practice., Materials and Methods: A cohort of women aged 18-49 with incident endometriosis was extracted from the 2006-2015 de-identified Clinformatics ® DataMart commercial insurance claims database (OptumInsight, Eden Prairie, MN). Endometriosis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 617.x on ≥1 inpatient or emergency department claim or ≥2 outpatient claims. Nonendometriosis control patients were exactly matched 4:1 to cases based on state, insurance plan type, and age (±1 year). Based on a literature review and expert consultation, 22 comorbidities were identified for analysis. The risk of developing a comorbidity post-index date was analyzed with stratified Cox proportional hazards models., Results: There were 26,961 cases and 107,844 controls. Mean age was 36 years. The adjusted risk of developing a comorbid condition among endometriosis cases was statistically significantly higher than the matched controls for all 22 comorbidities (p ≤ 0.001) and was at least twice as large for nine comorbidities (infertility/subfertility, ovarian cyst, uterine fibroids, pelvic inflammatory disorder, interstitial cystitis, irritable bowel syndrome, constipation/dyschezia, ovarian cancer, and endometrial cancer)., Conclusion: The incidence of developing many comorbidities was significantly higher among endometriosis patients compared with matched women without endometriosis. Additional research is needed to establish the implications for healthcare resource use.

Objective: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain., Methods: Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate., Results: Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV 550.8%) and 78.2% at 200 mg twice daily (Elaris EMIV 575.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.5% at 150 mg once daily (Elaris EM-IV 566.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV 567.2%).”After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings., Conclusion: Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use., Clinical Trial Registration: ClinicalTrials.gov, NCT01760954 and NCT02143713.

Introduction: The prevalence of endometriosis and the need for treatment in the USA has led to the need to explore the contemporary cost burden associated with the disease. This retrospective cohort study compared direct and indirect healthcare costs in patients with endometriosis to a control group without endometriosis., Methods: Women aged 18-49 years with endometriosis (date of initial diagnosis = index date) were identified in the Truven Health MarketScan ® Commercial database between 2010 and 2014 and female control patients without endometriosis were matched by age and index year. The following outcomes were compared: healthcare resource utilization (HRU) during the 12-month pre- and post-index periods (including inpatient admissions, pharmacy claims, emergency room visits, physician office visits, and obstetrics/gynecology visits), annual direct (medical and pharmacy) and indirect (absenteeism, short-term disability, and long-term disability) healthcare costs during the 12-month post-index period (in 2014 US$). Multivariate analyses were conducted to estimate annual total direct and indirect costs, controlling for demographics, pre-index clinical characteristics, and pre-index healthcare costs., Results: Overall, 113,506 endometriosis patients and 927,599 controls were included. Endometriosis patients had significantly higher HRU during both the pre- and post-index periods compared to controls (p < 0.0001, all categories of HRU). Approximately two-thirds of endometriosis patients underwent an endometriosis-related surgical procedure (including laparotomy, laparoscopy, hysterectomy, oophorectomy, and other excision/ablation procedures) in the first 12 months post-index. Mean annual total adjusted direct costs per endometriosis patient during the 12-month post-index period was over three times higher than that for a non-endometriosis control [$16,573 (standard deviation (SD) = $21,336) vs. $4733 (SD = $14,833); p < 0.005]. On average, incremental direct and indirect 12-month costs per endometriosis patient were $10,002 and $2132 compared to their matched controls (p < 0.005)., Conclusions: Endometriosis patients incurred significantly higher direct and indirect healthcare costs than non-endometriosis patients., Funding: AbbVie Inc.

Introduction: To examine the symptomatic burden of endometriosis on health-related quality of life (HRQL) in women in the United States (US)., Methods: A cross sectional web-based survey study was conducted among women using survey panels. The survey included study-specific questions and standardized HRQL questionnaires. Participants reviewed a list of endometriosis symptoms and selected all symptoms they had ever or were currently experiencing. For current symptoms, participants rated the severity and bothersomeness of each symptom. Participants completed the endometriosis health profile (EHP-30) core questionnaire. Descriptive analyzes were performed and multivariate regressions were run with each EHP subscale as a dependent variable to examine the impact of symptoms while controlling for age and comorbid conditions., Results: Mean age of the 1269 women was 34.3 ± 0.3; 78% were white. At least 75% reported having ever experienced: pelvic pain/cramping during their menstrual period, anxiety/stress, lower back pain or fatigue/weariness/anemia. EHP-30 scores ranged from 33.6 (95% CI: 31.4, 35.8) (social support) to 37.8 (95% CI: 35.5, 40.1) (control and powerlessness), indicating moderate HRQL impact. For all but one domain and one symptom, EHP-30 scores were significantly higher (worse) for women who had individual endometriosis-related symptoms than for those who did not. EHP-30 scores consistently deteriorated with each increase in the number of symptoms experienced and by increasing perceived disease severity. Pelvic pain/cramping during menstrual period, irregular periods and general abdominal pain were significantly associated with the EHP-30 domain scores in the regression models., Conclusion: Experiencing endometriosis symptoms is associated with lower HRQL. Importantly, as symptom severity and number of symptoms increase, HRQL further deteriorates.

Introduction: We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities., Methods: Women aged 18-49 years with endometriosis (N = 180,278) were extracted from 2006-2015 de-identified Clinformatics ® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient's index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre-post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis., Results: The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren's/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p < 0.001 except for headache (p = 0.045)]. Spending decreased significantly for fatigue, cystitis/UTI, and eczema [p < 0.001 except for fatigue (p = 0.048)] and was not statistically different for the other 11 comorbidities. Difference-in-differences estimates were significantly higher for comorbidity patients for all comorbidities except eczema (p ≤ 0.003). Mean 5-year total cumulative spending was $58,191 per endometriosis patient, of which between 11% and 23% was attributable to comorbidity-related medical claims., Conclusion: For all but one of the 22 comorbidities associated with endometriosis, comorbidity onset was associated with a relative increase in total healthcare spending., Funding: AbbVie Inc.

Introduction: Hysterectomy and laparoscopy are common surgical procedures used for the treatment of endometriosis. This study compares outcomes for women who received either procedure within the first year post initial surgery., Methods: The study used data from the Truven Health MarketScan claims databases from 2004 to 2013 to identify women aged 18-49 years who received an endometriosis-related laparoscopy or hysterectomy. Patients were excluded if they did not have continuous insurance coverage from 1 year before through 1 year after their endometriosis-related procedure, if they were diagnosed with uterine fibroids prior to or on the date of surgery (i.e., index date), or if they had a hysterectomy prior to the index date. The descriptive analyses examined differences between patients with an endometriosis-related laparoscopy or hysterectomy in regard to medications prescribed, complications, and hospitalizations during the immediate year post procedure., Results: The final sample consisted of 24,915 women who underwent a hysterectomy and 37,308 who underwent a laparoscopy. Results revealed significant differences between the cohorts, with women who received a laparoscopy more likely to be prescribed a GnRH agonist, progestin, danazol, or an opioid analgesic in the immediate year post procedure compared to women who underwent a hysterectomy. In contrast, women who underwent a hysterectomy generally had higher complication rates. Index hospitalization rates and length of stay (LOS) were higher for women who had a hysterectomy, while post-index hospitalization rates and LOS were higher for women who had a laparoscopy. For both cohorts, post-procedure complications were associated with significantly higher hospitalization rates and longer LOS., Conclusion: This study indicated significantly different 1-year post-surgical outcomes for patients who underwent an endometriosis-related hysterectomy relative to a laparoscopy. Furthermore, the endometriosis patients in this analysis had a considerable risk of surgical complications, subsequent surgeries, and hospital admissions, both during and after their initial therapeutic laparoscopy or hysterectomy., Funding: AbbVie.

Purpose: The objective of this review was to evaluate existing patient-completed screening questionnaires and/or symptom-based predictive models with respect to their potential for use as screening tools for endometriosis in adult women. Validated instruments were of particular interest., Methods: We conducted structured searches of PubMed and targeted searches of the gray literature to identify studies reporting on screening instruments used in endometriosis. Studies were screened according to inclusion and exclusion criteria that followed the PICOS (population, intervention, comparison, outcomes, study design) framework., Results: A total of 16 studies were identified, of which 10 described measures for endometriosis in general, 2 described measures for endometriosis at specific sites, and 4 described measures for deep-infiltrating endometriosis. Only 1 study evaluated a questionnaire that was solely patient-completed. Most measures required physician, imaging, or laboratory assessments in addition to patient-completed questionnaires, and several measures relied on complex scoring. Validation for use as a screening tool in adult women with potential endometriosis was lacking in all studies, as most studies focused on diagnosis versus screening., Conclusions: This literature review did not identify any fully validated, symptom-based, patient-reported questionnaires for endometriosis screening in adult women.

Background: Characterized by pain symptoms, endometriosis affects women's productivity in their prime working years., Objective: To evaluate the effect of individual endometriosis symptoms on household chore and employment productivity as measured by presenteeism and absenteeism in a population survey of women with endometriosis., Methods: An online survey of U.S. women was conducted to evaluate the prevalence of endometriosis, as well as symptoms, demographics, and clinical characteristics of the respondents. Women aged 18-49 years (inclusive) with endometriosis completed the Health-related Productivity Questionnaire to assess presenteeism and absenteeism for employed and household work. Descriptive statistics were used to describe the sample, survey responses, and the effect of endometriosis symptom severity on household chore and employment productivity. Regression analyses were performed to examine the effect of individual endometriosis symptoms on employment and household productivity lost because of presenteeism and absenteeism., Results: Of 59,411 women who completed the prevalence screener, 5,879 women (9.9%) met the inclusion criteria for completing the survey; 1,318 women (2.2%) reported endometriosis and at least 1 hour of scheduled household chores in the past 7 days. Of these, 810 women had least 1 hour of scheduled employment in the past 7 days. Mean age was 34.6 years (standard error [SE] ± 0.32); 77.2% of the women were white; 59.3% were married or in a civil union; and 59.1% were employed full or part time. Women with endometriosis had a weekly loss of an average of 5.3 hours (SE ± 0.4) because of employment presenteeism, 1.1 hours (SE ± 0.2) of employment absenteeism, 2.3 (SE ± 0.2) hours of household presenteeism, and 2.5 (SE ± 0.2) hours of household absenteeism. Hourly losses in employment and household chore productivity were significantly greater with increasing symptom severity (mild vs. severe: 1.9 vs. 15.8 total employment hours lost and 2.5 vs. 10.1 total household hours lost; P < 0.0001). Women who experienced 3 endometriosis symptoms concurrently lost a significantly greater number of employment hours because of absenteeism and presenteeism compared with those experiencing 1 or 2 symptoms (P < 0.001). Regression analyses showed that a range of endometriosis symptoms predicted employment and household losses because of presenteeism and absenteeism., Conclusions: There was a significant relationship between the number and patient-reported severity of endometriosis symptoms experienced and hours of employment and household productivity lost because of presenteeism and absenteeism. Study findings indicate a need for guidance strategies to help women and employers manage endometriosis so as to reduce productivity loss., Disclosures: The design and financial support for this study was provided by AbbVie. AbbVie participated in data analysis, interpretation of data, review, and approval of the manuscript. Coyne and Gries are employees of Evidera- Evidence, Value & Access by PPD and were paid scientific consultants for AbbVie in connection with this study. Soliman, Castelli-Hayley, and Snabes are AbbVie employees and may own AbbVie stock or stock options. Surrey is affiliated with Colorado Center for Reproductive Medicine and was paid by AbbVie as a consultant for this project. Surrey serves as a consultant for AbbVie outside of this project. All authors participated in data analysis and interpretation, and contributed to the development of the manuscript. The authors maintained control over the final contents of the manuscript and the decision to publish. Study concept and design were contributed by Soliman, Coyne, Gries, and Castelli-Haley. Soliman, Castelli-Haley, Coyne, and Gries collected the data, and data interpretation was performed by Snabes, Surrey, Soliman, Coyne, and Gries. The manuscript was written and revised by Soliman, Coyne, and Gries, along with the other authors.

Background: We aimed to quantify the time to diagnosis among women with endometriosis in the United States (US) and to identify patient- and physician-related factors affecting diagnostic delay., Patients and Methods: An online cross-sectional survey was conducted from August 6, 2012, through November 14, 2012. Respondents aged 18-49 years who reported a physician's diagnosis/suspicion of endometriosis within the previous 10 years were included. Endometriosis-related symptoms and diagnostic history were captured and summarized. Univariate analyses identified factors associated with time from symptom onset to first consultation and from first consultation to diagnosis., Results: Of 638 respondents included, most (56%) reported seeking care for at least one of the following symptoms: menstrual pain (31.6%), nonmenstrual pain (27.3%), and pain during sex (7.5%). Most diagnoses (84%) were made by obstetricians/gynecologists; 49% of diagnoses were surgical versus 51% nonsurgical. Mean time from symptom onset to diagnosis was 4.4 years. Mean time to first consultation was shorter among women aged 40-49 years versus those aged <18 years (14.2 vs. 43.5 months; p < 0.0001) and those consulting for symptoms versus routine/other care (27.9, 24.9, and 28.4 months for menstrual pain, nonmenstrual pain, and pain during sex, respectively, vs. 61.4 months; all p < 0.01). Mean time from first consultation to diagnosis was shorter among women aged 40-49 years versus those aged <18 years (12.4 vs. 34.5 months; p = 0.0009) and those diagnosed by obstetricians/gynecologists versus nonobstetricians/gynecologists (21.5 vs. 40.3 months; p = 0.041)., Conclusions: Time to endometriosis diagnosis appears to have shortened in the US. Better patient and physician education regarding symptomatology may contribute to further gains.

Background: Hysterectomy and laparoscopy are the two most common surgical options used to treat women with endometriosis, yet the disease may still recur. This study aimed to determine the long-term retreatment rates among endometriosis patients in the United States who received either hysterectomy or laparoscopy., Materials and Methods: Patients aged 18-49 years with endometriosis who underwent hysterectomy or laparoscopy were identified in the Truven Health MarketScan claims database (2004-2013). The retreatment rate up to 8 years after the initial surgery was estimated using Kaplan-Meier survival analysis. The relative risk of retreatment among patients with hysterectomy versus laparoscopy was assessed using a Cox proportional hazard model., Results: A total of 24,915 patients with endometriosis who underwent hysterectomy and 37,308 patients with endometriosis who underwent laparoscopy were identified. The estimated retreatment rates were 3.3%, 4.7%, and 5.4% in the 2nd, 5th, and 8th year following hysterectomy, respectively, while the rates following laparoscopy were 15.8%, 27.5%, and 35.2%, respectively. The hazard ratio of retreatment was 0.157 (95% confidence interval [CI]: 0.146-0.169) comparing hysterectomy to laparoscopy. In the sensitivity analysis, which expanded the definition of retreatment by including medical treatments, the retreatment rate increased by a factor of 11-14 for the hysterectomy cohort and by a factor of 2-4 for the laparoscopy cohort, and the hazard ratio of retreatment rate for hysterectomy versus laparoscopy was 0.490 (95% CI: 0.477-0.502)., Conclusions: Our study results indicated that the disease retreatment rate after laparoscopy is high among patients with endometriosis; even hysterectomy does not guarantee freedom from retreatment.

Objective: To compare direct and indirect costs between endometriosis patients who underwent endometriosis-related surgery (surgery cohort) and those who have not received surgery (no-surgery cohort)., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): Endometriosis patients (aged 18-49 years) with (n = 124,530) or without (n = 37,106) a claim for endometriosis-related surgery were identified from the Truven Health MarketScan Commercial and Health and Productivity Management databases for 2006-2014., Intervention(s): Not applicable., Main Outcome Measure(s): Primary outcomes were healthcare utilization during 12-month pre- and post-index periods, annual direct (healthcare) and indirect (absenteeism and short- and long-term disability) costs during the 12-month post-index period (in 2014 US dollars). Indirect costs were assessed for patients with available productivity data., Result(s): Patients in the surgery cohort had significantly higher healthcare resource utilization during the post-index period and had mean annual total adjusted post-index direct costs approximately three times the costs among patients in the no-surgery cohort ($19,203 [SD $7,133] vs. $6,365 [SD $2,364]; average incremental annual direct cost = $12,838). The mean cost of surgery ($7,268 [SD $7,975]) was the single largest contributor to incremental annual direct cost. Mean estimated annual total indirect costs were $8,843 (surgery cohort) vs. $5,603 (no-surgery cohort); average incremental annual indirect cost = $3,240., Conclusion(s): Endometriosis patients who underwent surgery, compared with endometriosis patients who did not, incurred significantly higher direct costs due to healthcare utilization and indirect costs due to absenteeism or short-term disability. Regardless of the surgery type, the cost of index surgery contributed substantially to the total healthcare expenditure., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background/aims: To estimate the prevalence of diagnosed endometriosis (DE) in women in the United States and assess the associated symptomatic burden., Methods: An online, cross-sectional survey of women aged 18-49 years was conducted from August 6, 2012, through November 14, 2012. Survey data (weighted by age, race, education, income, geographical distribution, and propensity score) were used to estimate the prevalence and symptomatic burden of DE in women in the United States. Weighted logistic regressions were used to assess differences in symptom burden between women with and without endometriosis., Results: The prevalence of DE was estimated at 6.1% (2,922 of 48,020 women surveyed); 52.7% of women were 18-29 years of age when they were diagnosed with endometriosis. Most (86.2%) women experienced symptoms before diagnosis. More women with (vs. without) DE had menstrual pelvic pain/cramping (52.7 vs. 45.2%), non-menstrual pelvic pain/cramping (36.7 vs. 14.3%), infertility (11.6 vs. 3.4%), and dyspareunia (29.5 vs. 13.4%). Women with endometriosis were also more likely to report severe symptoms (OR (95% CI) 2.7 (2.3-3.1) for menstrual pelvic pain/cramping, 2.2 (1.7-2.9) for non-menstrual pelvic pain/cramping, and 2.4 (1.8-3.2) for dyspareunia)., Conclusion: The prevalence of DE among US women is notable, and affected women experience a substantial symptom burden., (© 2016 S. Karger AG, Basel.)

Objective To compare subsequent endometriosis-related surgery following initial laparoscopy among women treated with leuprolide acetate (LA) or other endometriosis therapies versus women who received no pharmacotherapy. Research design and methods This retrospective cohort analysis utilized MarketScan Commercial claims data. Women with endometriosis aged 18-49 who underwent laparoscopy between 1 January 2005 and 31 December 2011 were identified using diagnosis and procedures codes and were categorized into four cohorts based on claims within 90 days of laparoscopy: surgery plus adherent LA, surgery plus non-adherent LA, surgery plus other therapy, and surgery alone. Patients with proportion of days covered ≥0.80 in the 6 months after laparoscopy were considered adherent to LA. Main outcome measures Subsequent endometriosis-related surgery (laparoscopy, laparotomy or other excision/ablation/fulguration of endometriosis lesions, oophorectomy, or hysterectomy) was measured in the 6 and 12 months following initial laparoscopy. Risk of subsequent surgery was compared using multivariable Cox proportional hazards modeling. Results Most women were treated with surgery only (n = 9865); fewer were treated with LA (adherent: n = 202; non-adherent: n = 490) or other therapies (n = 230). The proportion of patients with subsequent surgery ranged from 2.0% to 10.0% during the 6 month follow-up (12 month: 9.7% to 13.5%). Adherent LA use was associated with significantly lower risk of surgery compared to surgery alone (hazard ratio [HR] = 0.31, p = 0.020) while use of other therapies was associated with significantly higher risk (HR = 1.51, p = 0.045) over the 6 month follow-up. There was no significant difference between the surgery plus non-adherent LA and surgery only cohort over 6 months (p = 0.247). The association between adherent LA and subsequent surgery was not significant over the 12 month follow-up. Conclusion Therapy with LA after laparoscopy for endometriosis was associated with lower risk of subsequent surgery at 6 months among women who were adherent to LA. Key limitations include lack of ability to capture disease severity which may have resulted in uncontrolled confounding.

Background: Endometriosis affects over 10 million women in the United States. Depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, has been used extensively for the treatment of women with endometriosis but is associated with hypoestrogenic symptoms and bone mineral density loss. The concomitant use of add-back therapies, specifically norethindrone acetate (NETA), can alleviate these adverse effects., Objective: To compare adherence to and persistence with LA treatment and time to endometriosis-related surgery among women treated with NETA and women treated with LA plus other add-back therapies or LA only., Methods: This retrospective analysis was conducted using Truven Health MarketScan Commercial Claims and Encounters Database. Women with a diagnosis of endometriosis (ICD-9-CM code 617.xx) who initiated LA (index date) in 2005-2011 were selected for inclusion. Additional requirements were 12 months of continuous enrollment pre- and post-index and no evidence of endometriosis-related surgeries pre-index or up to 30 days post-index; no pre-index use of estrogen or noncontraceptive hormones; and no diagnoses of uterine fibroids, malignant neoplasms, infertility, or pregnancy. Patients were characterized as using NETA; other add-back therapies (estrogens, progestins, or estrogen-progestin combinations); or no add-back therapy. Adherence to and persistence with LA were measured over the 6 months following the index date using outpatient medical and pharmacy claims. Patients were considered adherent if their proportion of days covered was greater than or equal to 0.80. Persistence was operationalized as time to discontinuation, defined as a continuous gap of > 60 days without LA on hand. Time to endometriosis-related surgery (laparotomy, laparoscopy, excision/ablation/fulguration, oophorectomy, and hysterectomy) was measured over the 12 months following the index date. Surgeries were identified from inpatient and outpatient medical claims using procedure codes. Outcomes were compared among cohorts using multivariable logistic and Cox proportional hazards regression models controlling for demographics and baseline clinical characteristics., Results: The final sample included 3,114 women, with a mean age of 36.9 years. The majority of women used LA only with no add-back therapy (n = 1,963, 63.0%), while 15.1% (n = 470) used NETA, and 21.9% (N = 681) used other add-back therapies. During the 6-month follow-up, more patients in the LA plus NETA cohort were adherent to LA therapy compared with LA only (47.2% vs. 31.5%, P < 0.001), and fewer patients discontinued (37.9% vs. 59.6%, P < 0.001). Additionally, fewer patients underwent endometriosis-related surgery in the 12 months after LA initiation in the LA plus NETA cohort (12.6% vs. 16.9%, P = 0.021). In multivariable models, women who initiated LA plus NETA or LA plus other add-back therapies had a higher likelihood of being adherent to LA than LA only patients (OR = 1.91, 95% CI = 1.55-2.36 and OR = 1.95, 95% CI = 1.63-2.34) and lower likelihood of LA discontinuation (HR = 0.54, 95% CI = 0.46-0.63 and HR = 0.59, 95% CI = 0.52-0.68). NETA patients had a lower surgery rate in the 12-month post-index period compared with other add-back patients (HR = 0.68, 95% CI = 0.50-0.93) or LA only patients (HR = 0.69, 95% CI = 0.52-0.92)., Conclusions: For women with endometriosis, treatment with LA and concomitant add-back therapies was associated with better adherence to and persistence with LA over the 6 months following initiation, compared with treatment with LA only. The increased adherence and persistence to LA may translate into decreased need for surgical intervention, although fewer endometriosis-related surgeries were only observed in the 12 months following LA initiation for patients using concomitant NETA add-back therapy. These results support an increased and earlier use of NETA add-back therapy among women who initiate LA., Disclosures: This study was funded by AbbVie, which also markets the endometriosis drugs Lupron and Lupaneta Pack. AbbVie participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. Soliman and Castelli-Haley are employees of AbbVie and may own AbbVie stock or stock options. Bonafede and Farr are employees of Truven Health Analytics, which received a research contract to conduct this study with and on behalf of AbbVie. Winkel is a clinical professor in the Department of Obstetrics and Gynecology at Georgetown University in Washington, DC, and has served in a consulting role on research to AbbVie for this project. An earlier version of the current research was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting; Philadelphia, PA; May 2015. All authors participated in data analysis and interpretation and contributed to the development of the manuscript.

Study Question: What is the economic burden of endometriosis?, Summary Answer: The identified studies indicate that there is a significant economic burden associated with endometriosis, as observed by both direct and indirect costs., What Is Known Already: Two previous systematic literature reviews suggested that there were considerable direct costs associated with endometriosis and there was a general lack of measurement of indirect costs., Study Design, Size, Duration: We performed a systematic literature review. MEDLINE and EMBASE databases from 2000 to 2013 were searched. The literature search was limited to human studies of patients with endometriosis. Papers in languages other than English were excluded., Participants/materials, Setting, Methods: Studies reporting direct or indirect costs among patients with endometriosis were considered for inclusion. Direct costs included inpatient, outpatient, surgery, drug and other healthcare service cost. Indirect costs were related to absenteeism and presenteeism (lost productivity at work)., Main Results and the Role of Chance: After evaluating the 1396 articles in the search results, 12 primary studies that reported direct or indirect costs associated with endometriosis were identified and included in the data extraction. Three of the studies were conducted in the USA, one study each was conducted in Austria, Belgium, Brazil, Canada, Finland, Germany and Italy, and two studies included data from 10 countries. Significant variability was observed in the reviewed studies in methodology, including data source, cost components considered and study perspective. Estimates of total direct costs ranged from $1109 per patient per year in Canada to $12 118 per patient per year in the USA. Indirect costs of endometriosis ranged from $3314 per patient per year in Austria to $15 737 per patient per year in the USA., Limitations, Reasons for Caution: The studies identified in the systematic literature review varied greatly by study methodology as well as by country owing to different healthcare systems and costs of healthcare services, which contributed to large variations in the direct and indirect cost estimates., Wider Implications of the Findings: A majority of the studies we found were published after the periods covered in the prior systematic literature reviews, which provided substantial contributions to an understanding of the economic burden of endometriosis, especially in the area of indirect costs. The long-term burden of endometriosis following diagnosis is still under-studied, which is a concern given the chronic nature of the disease and the substantial recurrence of endometriosis symptoms., Study Funding/competing Interests: This study was funded by AbbVie, which also develops the oral GnRH antagonist elagolix (in collaboration with Neurocrine Biosciences) for the management of endometriosis and uterine fibroids. A.M.S. is an employee of AbbVie and currently owns AbbVie stocks. H.Y., E.X.D. and C.K. are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. C.W. is a Clinical Professor at the Department Obstetrics and Gynecology at Georgetown University in Washington, DC, USA and has served in a consulting role to AbbVie for this project., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To assess healthcare resource utilization and costs during the 5 years before and 5 years after diagnosis among women with endometriosis, in comparison with women without endometriosis., Design: Longitudinal, retrospective, case-control study., Setting: None., Patient(s): A total of 37,570 matched pairs of women with and without (controls) endometriosis were identified from the Truven Health MarketScan claims database (2000-2010)., Intervention(s): None., Main Outcome Measure(s): Annual healthcare resource utilization and costs (in 2010 US dollars) were evaluated for the 5 years before and 5 years after diagnosis., Result(s): Mean patient age at index (first diagnosis) date was 36.4 years for endometriosis patients and controls. Endometriosis patients had a higher utilization of outpatient and emergency room services during each pre- and postindex year, and a higher utilization of inpatient services during the last preindex year and all 5 postindex years. Total costs were highest in the first postindex year for endometriosis patients, reaching $13,199, compared with $3,747 for controls. Annual costs were significantly higher for patients than controls during each pre- and postindex year; overall, the cost difference was $26,305 over 10 years: $7,028 in the 5 years before diagnosis and $19,277 in the 5 years after diagnosis., Conclusion(s): Endometriosis poses a significantly high economic burden, both before and after diagnosis. The highest resource utilization and costs experienced by endometriosis patients occur in the first year after diagnosis., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one's life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.

PurposeElagolix is an oral gonadotropin-releasing hormone antagonist approved in the United States for the management of moderate to severe pain associated with endometriosis. We performed a real-world evaluation of the demographic and clinical characteristics of women diagnosed with endometriosis who were initiating elagolix therapy in the United States.Patients and methodsThis retrospective cohort database analysis included women 18-49 years of age with ≥1 pharmacy claim for elagolix between August 2018 and December 2019 from the Copyright © 2020 Truven Health Analytics LLC. All Rights Reserved. Women had continuous medical and pharmacy health plan enrollment during the baseline period (year immediately preceding the index date [date of earliest elagolix claim]) and had ≥1 medical claim with endometriosis (International Classification of Diseases [ICD]-9/10 code [617.x and N80.x]) on or before the index date. Baseline demographics, comorbidities, ICD code-based endometriosis anatomic site, endometriosis-related treatments, and pain symptoms were summarized descriptively.ResultsThe study included 2083 patients with mean age at baseline of 33.2 ± 8.1 years. Comorbidities most commonly recorded were non-cancer, non-endometriosis pain (59.5%), including arthritis/joint pain (43.7%) and back/neck pain (31.7%), and mental disorder (40.7%), including anxiety (32.7%). The majority of endometriosis diagnosis codes recorded referred to unspecified location (52.3%) and pelvic peritoneum (23.0%); 61.0% of patients received a medical endometriosis-related treatment in the baseline period, with the most common treatments being contraceptives (various routes of administration, 40.2%) and progestins (31.7%). Additionally, 35.4% of the patients received an endometriosis-related surgery during baseline, with the most common being laparoscopy (33.2% of all patients). Opioids were used during the baseline period by 57.3% of the patients. For pain symptoms, 71.5%, 30.4%, and 19.3% of the patients had claims for pelvic pain, dysmenorrhea, and dyspareunia, respectively.ConclusionEndometriosis therapies were used by a significant proportion of patients with endometriosis in the year immediately preceding elagolix initiation.