Endometriosis, a condition in which uterine tissue grows outside the uterus, is a debilitating disease, affecting millions of women and costing the United States approximately $78 billion annually in pain-related disability. It is also the leading cause of chronic pelvic pain (CPP), which is often unresponsive to existing treatments. Adolescent women with the disease are at particular risk as there are often significant diagnostic delays, which in turn can exacerbate pain. Research and treatment guidelines for adolescents with endometriosis are largely based on studies for adult women due to the limited number of studies focusing on adolescents. The current paper critically reviews the literature as it pertains to endometriosis pathophysiology, mechanisms contributing to CPP, and treatment implications and recommendations with a focus on gaps related to adolescents.

Pain and stress are both phenomena that challenge an individual's homeostasis and have significant overlap in conceptual and physiological processes. Allostasis is the ability to adapt to pain and stress and maintain homeostasis; however, if either process becomes chronic, it may result in negative long-term outcomes. The negative effects of stress on health outcomes on physiology and behavior, including pain, have been well documented; however, the specific mechanisms of how stress and what quantity of stress contributes to the maintenance and exacerbation of pain have not been identified, and thus pharmacological interventions are lacking. The objective of this brief review is to: 1. identify the gaps in the literature on the impact of acute and chronic stress on chronic pain, 2. highlight future directions for stress and chronic pain research; and 3. introduce the Pain-Stress Model in the context of the current literature on stress and chronic pain. A better understanding of the connection between stress and chronic pain could provide greater insight into the neurobiology of these processes and contribute to individualized treatment for pain rehabilitation and drug development for these often comorbid conditions.

Chronic pain and opioid misuse are both common in pediatric populations and associated with a range of negative adverse outcomes that may persist into adulthood. While the association between chronic pain, opioid prescribing, and opioid-related adverse consequences is reasonably well established in adults, the relation in pediatric patients is not well understood. The present review draws from the available literature on chronic and acute pediatric pain prevalence and treatment, opioid misuse, and adolescent substance use to address knowns and unknowns of comorbid pediatric chronic pain and opioid misuse. Gaps in knowledge regarding the prevalence and etiology of co-occurring chronic pain and opioid misuse are identified. Hypothesized, modifiable risk factors associated with both pediatric pain and opioid misuse are considered. Due to a lack of empirically supported integrated treatments for co-morbid chronic pain and opioid misuse in youth, this review examines the evidence base and best practices from both the chronic pain and opioid treatment literature to guide treatment recommendations for these co-morbid conditions in youth. Recommendations are then provided to promote screening and mitigate risk of chronic pain and opioid misuse across a range of medical settings. Lastly, a comprehensive agenda to prevent and treat chronic pain and opioid misuse in adolescents and young adults is discussed.

Endometriosis is a chronic condition affecting ~10% of women globally. Little is known about the impact of the coronavirus disease 2019 (COVID-19) pandemic on their care. This brief report is aimed to explore the impact of COVID-19 on the care of people with endometriosis around the world, their priorities in relation to their clinical care during and coming out of the pandemic, and whether they believed that endometriosis makes them more vulnerable to COVID-19. An internet-based survey collected data in five languages between May 11, 2020, and June 8, 2020. Only participants with a surgical or radiological diagnosis of endometriosis aged 18 years or over were included. A total of 6,729 eligible respondents completed the survey with 80.7% [95% CI (79.7, 81.6)] reporting a negative impact on their care. This included difficulties obtaining medication (20.3%), cancelled/postponed gynaecology appointments (50.0%), and cancelled/postponed procedures (37.2%). More than half worried that their endometrioses make them more vulnerable to COVID-19 [54.2%; 95% CI (53.0, 55.4)]. The top three priorities were remarkably consistent around the world: contact with gynaecologists, knowing when procedures would be performed, and support with mental health (20.3% prioritising this aspect during the pandemic and 13.0% as restrictions begin to ease). This study shows the substantial impact the COVID-19 pandemic has had on people with endometriosis and describes how they would like care prioritised moving forwards. The findings regarding significant support needs for mental health add further weight to the growing recognition of attending to such issues as part of good patient-centred care.

Awareness and visibility of transgender individuals have grown exponentially. However, conceptualizing sexual and reproductive health (SRH) as “women's” or “men's” health services further marginalizes transgender and gender-expansive (TGE) youth. Multiple reviews and commentaries have been published on the topic of SRH care for adults under the umbrella term of sexual and gender minorities, all with a call to action for more inclusive care and the need for more clinical research involving TGE individuals, and notably, TGE youth. Results from adult TGE studies are often translated to describe adolescent models. However, models specific to adolescent TGE populations are needed to understand their unique SRH needs. This review will describe the current literature relating to SRH needs of TGE youth and adults, highlighting key areas with significant disparities in need of further research. This comprehensive summary will also provide recommendations for clinicians and researchers with the goal of improving SRH care and obtaining wider representation in both clinical settings and research directed toward TGE youth.

Chronic pain is a significant socio-economic and humanitarian burden affecting both children and adults. 1,2 With chronic pain occurring across the lifespan, many studies have focused on pain in children, adolescents, and adults while less is known specifically about pain during emerging adulthood. Research is gaining momentum, 3-5 but the experience of the emerging adult-parent dyad has not been considered in the context of chronic pain, particularly with the emergence of a parenting style described as helicopter parenting. Often defined

IntroductionChronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL).MethodsThe study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N = 230) and four pain groups: endometriosis-associated pain (EAP, N = 237), interstitial cystitis/bladder pain syndrome (BPS, N = 72), comorbid endometriosis-associated pain and BPS (EABP, N = 120), and pelvic pain only (PP, N = 127).ResultsClinical profiles of women with CPP (13–50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p < 0.001) on the pain intensity scales for non-cyclical pelvic pain and higher than both the BPS and PP groups (p < 0.001) on the dysmenorrhoea scale. The EABP group also had significantly higher scores for dyspareunia (p < 0.001), even though more than 50% of sexually active participants in each pain group reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months. Scores for the QoL questionnaire (SF-36) reveal that CPP patients had significantly lower QoL across all SF-36 subscales (p < 0.001). Significant effects were also observed between the pain groups for pain interference with their work (p < 0.001) and daily lives (p < 0.001), with the EABP suffering more compared to the EAP and PP groups (p < 0.001).DiscussionOur results demonstrate the negative impact that chronic pain has on CPP patients' QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed.

Study question: Do subgroups of women with chronic pelvic pain (CPP) report different clinical symptoms and differing impact of pain on their quality of life? Summary answer: Clinical profiles of women with CPP show variability of clinical symptoms both within and between subgroups. However, there is an obvious negative impact of pain on the patients' lives across all subgroups with the comorbid endometriosis and bladder pain symptoms group (EABP) presenting with the higher pain intensities and the lower quality of life. What is known already: CPP is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. The clinical presentation of CPP is varied and there are frequently comorbid conditions both within and outside the pelvis. Evidence from the literature show that there is an overlap of symptoms in chronic pain conditions whatever the underlying cause which suggests that chronic pain could be a condition itself. Study design, size, duration: The study is part of The Translational Research in Pelvic Pain (TRiPP) project (https://www.imi-paincare.eu/PROJECT/TRIPP/) which is a cross-sectional observational cohort study. The present study includes 769 female participants sampled from two existing endometriosis-focused cohort studies in Oxford, UK and Boston, MA, USA and newly recruited from the Instituto de Biologia Molecular e Celular (IBMC)) in Porto. The participants completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this study population we defined a control group (reporting no pelvic pain, no bladder pain syndrome (BPS), and no endometriosis diagnosis, N=230) and four pain groups: endometriosis-associated pain (EAP, N=237), (BPS, N=72), comorbid endometriosis-associated pain and BPS (EABP, N=120), and pelvic pain only (PP, N=127). Participants/materials, setting, methods: All participants were women of reproductive age (13-50 years) and were recruited at three different sites: Oxford (University of Oxford), Boston (Boston Center for Endometriosis (BCE)) and Porto (Instituto de Biologia Molecular e Celular (IBMC)). The questionnaire included: demographics; reproductive history; pelvic pain intensity assessed using 10-point numerical rating scales (NRS) for dysmenorrhoea, non-cyclical pain, dyspareunia and bladder pain; medical comorbidities; factors relieving and worsening pain; quality of life assessed using the SF-36 questionnaire; and pain catastrophising. Main results and the role of chance: The EAP (Mean:7.37) and EABP (Mean:7.88) groups scored higher on the pain intensity scales for non-cyclical pelvic pain than the PP (Mean:6.82) group (p<0.001) and higher on the dysmenorrhoea scale than both the BPS and PP groups (p<0.001). The EABP (Mean:6.61) and BPS (Mean:6.52) groups had significantly higher bladder pain scores than the EAP (Mean:0.95) and PP (Mean:0.78) (p<0.001). The EABP group also had significantly higher pain scores for dyspareunia (p<0.001), even though more than 50% of participants (who were sexually active) in each of the pain groups reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months. Exploring the factors reported to worsen or relieve pain found that across the pain groups the three most reported factors for worsening pelvic pain were: stress (23.6%), full bladder/urinating (23.3%) and exercising (20.2%). The most common factors for relieving pelvic pain were: pain medication (31.4%), lying down (31.0%), and use of a heat pad (29.5%). Analysis of the quality-of-life questionnaire (SF-36) subscales revealed significant differences between the study groups across all SF-36 subscales (p<0.001). In line with the pain results the EABP group reported the negative highest impact across all the health measures while the PP group's profile was closest to the control group's profile. Significant effects were also observed between the pain groups for pain interference with their work (F(3,209)=9.76, p<0.001) and daily lives (F(3,244)=10.51, p<0.001), with the EABP suffering more compared to the EAP and PP groups (p<0.001). Limitations, reasons for caution: Data for this study were derived predominantly from existing cohorts where data have been collected over time and thus different versions of questionnaires have been used. Thus, for some questions only a subgroup may have had an opportunity to complete the measure of interest. Recruitment of participants was impacted due to the COVID-19 pandemic. As a result, sample sizes overall were smaller than originally designed, and our BPS group was predominantly identified from gynaecological rather than urological clinics making it potentially different from other published BPS cohorts. Wider implications of the findings: Overall, our results demonstrate the negative impact that chronic pain has on CPP patients' quality of life and suggests that further exploration of interventions targeting quality of more broadly is important. Furthermore, it demonstrates the importance of dyspareunia in women with CPP, highlighting the need for more research in this area. Importantly, we show significant differences between the sub-groups of CPP suggesting the need for better patient stratification in future clinical studies and trials. However, the marked variability both within and between CPP sub-groups raises the question whether subgrouping on the basis of clinical diagnosis is the most appropriate strategy or whether alternative approaches could be identified allowing prioritisation of treatments better suited to the individual patient. Study funding/competing interest(s): This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777500. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA Companies. Financial support was provided by the J. Willard and Alice S. Marriott Foundation for establishment of and baseline data collection within the A2A cohort - from which the Boston-based TRiPP population was sampled. Clinical Trial registration ID #: NCT04001244