Endometriosis: Etiology, pathobiology, and therapeutic prospects

Saunders, Philippa T. K.; Horne, Andrew W

doi:10.1016/j.cell.2021.04.041

Cited by 434 publications

(420 citation statements)

References 173 publications

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“…Although the natural history and pathophysiology of endometriosis are not fully understood [9], it is well-established that symptoms of endometriosis can be progressive and recurrent. These symptoms include, but are not limited to, cyclic pelvic pain (dysmenorrhea), acyclic pelvic pain that can be chronic (lasting more than six months), painful vaginal intercourse (dyspareunia), painful urination (dysuria), painful bowel movements (dyschezia), infertility, fatigue, heavy menstrual bleeding, and intermenstrual bleeding [1,2,4,[10][11][12], with greater risk of pain-associated conditions such as fibromyalgia, rheumatoid arthritis [13], and migraine [14].…”

Section: Epidemiology Natural History and Comorbiditiesmentioning

confidence: 99%

Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay

Sims

Gupta

Missmer

et al. 2021

IJERPH

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Endometriosis is a chronic gynecological disease that affects approximately 1 in 10 women of reproductive age. Symptoms of severe pelvic pain, infertility, fatigue, and abnormal menstruation can cause significant negative effects on an individual’s physical and mental health, including interactions with their family, friends, and health care providers. Stigma associated with endometriosis has been under-studied and is rarely discussed in current literature. Herein, this paper aims to provide a brief overview of published literature to explore and establish the plausibility of stigma as a driver of suboptimal psychosocial well-being and diagnostic delay among individuals living with endometriosis. We present the clinical characteristics and physical and mental health consequences associated with endometriosis, highlight several theoretical constructs of stigma, and review the limited studies documenting women’s lived experiences of endometriosis-related stigma. To mitigate harmful effects of this phenomenon, we recommend increasing efforts to assess the prevalence of and to characterize endometriosis-related stigma, implementing awareness campaigns, and developing interventions that combat the multidimensional negative effects of stigma on timely care, treatment, and quality of life for individuals living with endometriosis.

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Section: Epidemiology Natural History and Comorbiditiesmentioning

confidence: 99%

Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay

Sims

Gupta

Missmer

et al. 2021

IJERPH

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“…Endometriosis is an estrogen-dependent, chronic inflammatory condition that contains tissue that resembles an endometrium with one or more of the following: stromal fibroblasts, epithelial cells, immune cells, and nerves and vascular/perivascular cells in sites outside the uterine cavity ( Zondervan et al 2020 , Saunders & Horne 2021 ). Moreover, it affects approximately 10% of all reproductive-aged women and is associated with pain and infertility ( Hughes et al 2015 , Zondervan et al 2020 , Saunders & Horne 2021 ). The treatment choice will depend on age at diagnosis, disease stage, the patient’s symptoms, priorities and expectations, reproductive plans, safety, adverse effects incidence, tolerability, and cost ( Ferrero et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Nonhormonal therapy for endometriosis based on energy metabolism regulation

Kobayashi

Shinmoto

Imanaka

2021

Reproduction and Fertility

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Objectives: Ovarian function suppression is the current pharmacotherapy of endometriosis with limited benefit and adverse effects. New therapeutic strategies other than hormonal therapy are developed based on the molecular mechanisms involved in the hypoxic and oxidative stress environments and metabolism unique to endometriosis. Methods: A literature search was performed between January 2000 and March 2021 in the PubMed database using a combination of specific terms. Results: Endometriosis-associated metabolic changes have been organized into four hallmarks: (1) glucose uptake, (2) aerobic glycolysis, (3) lactate production and accumulation, and (4) metabolic conversion from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Endometriotic cells favor glycolytic metabolism over mitochondrial OXPHOS to produce essential energy for cell survival. Hypoxia, a common feature of the endometriosis environment, is a key player in this metabolic conversion, which may lead to glucose transporter overexpression, pyruvate dehydrogenase kinase 1 (PDK1) and lactate dehydrogenase kinase A (LDHA) activation, and pyruvate dehydrogenase complex inactivation. Evading mitochondrial OXPHOS mitigates excessive generation of reactive oxygen species (ROS) that may trigger cell death. Therefore, the coinactivation of LDHA and PDK1 can induce the accumulation of mitochondrial ROS by converting energy metabolism to mitochondrial OXPHOS, causing endometriotic cell death. Conclusion: Metabolic pattern reconstruction in endometriotic lesions is a critical factor in cell survival and disease progression. One therapeutic strategy that may avoid hormone manipulation is focused on mitigating metabolic changes that have been detected in cells/tissues from women with endometriosis.

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“…Endometriosis has an estimated prevalence of 6-15% of women in their reproductive age worldwide (5)(6)(7). The etiology of endometriosis is not fully understood (8). There are several hypotheses regarding the etiopathogenetic mechanisms of endometriosis; the most widely accepted transportation theory assumes that viable endometrial cells circulate back during menstruation through the tubes (menstrual reflux) and cluster at neighboring pelvic structures (9).…”

Section: Introductionmentioning

confidence: 99%

The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls—A Mixed-Methods Study

Olliges¹,

Hoffmann²,

Weber³

et al. 2021

Front. Glob. Womens Health

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Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls.Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software.Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they “no longer felt like themselves.” Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p < 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p < 0.001; Short-Form Health Survey-12), stress ratings (p < 0.001; Patient Health Questionnaire-15) and functional well-being (p < 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p < 0.01).Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.

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Endometriosis: Etiology, pathobiology, and therapeutic prospects

Cited by 434 publications

References 173 publications

Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay

Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay

Nonhormonal therapy for endometriosis based on energy metabolism regulation

The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls—A Mixed-Methods Study

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