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Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment.F1000Research 2019Endometriosis is an enigmatic disease that could start at birth. Its pathogenesis is supported by different theories. Accumulating facts relate it to a multigenic... (Review)
Review
Endometriosis is an enigmatic disease that could start at birth. Its pathogenesis is supported by different theories. Accumulating facts relate it to a multigenic disorder. In this review of recent publications, the principal symptoms of the disease, pain and infertility, as well as its pathogenesis, diagnosis, and classification will be addressed. Endometriosis presents three main variants: superficial peritoneal disease, deep infiltrating endometriosis, and ovarian endometriomas. The management of the disease, surgery, and medical and alternative therapies will be discussed. Special reference will be made to the quality of surgery and how to understand patients with endometriosis and endometriosis.
Topics: Dysmenorrhea; Endometriosis; Female; Humans; Infertility, Female; Laparoscopy
PubMed: 31069056
DOI: 10.12688/f1000research.14817.1 -
Fertility and Sterility Sep 2012Originally described over three hundred years ago, endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations.... (Review)
Review
Originally described over three hundred years ago, endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations. Endometriosis is an inflammatory, estrogen-dependent condition associated with pelvic pain and infertility. This work reviews the disease process from theories regarding origin to the molecular basis for disease sequelae. A thorough understanding of the histopathogenesis and pathophysiology of endometriosis is essential to the development of novel diagnostic and treatment approaches for this debilitating condition.
Topics: Animals; Cell Adhesion; Cell Survival; Endometriosis; Endometrium; Female; Humans; Inflammation; Neovascularization, Physiologic
PubMed: 22819144
DOI: 10.1016/j.fertnstert.2012.06.029 -
Frontiers in Endocrinology 2021Understanding the pathophysiology of endometriosis is changing our diagnosis and treatment. Endometriosis lesions are clones of specific cells, with variable... (Review)
Review
Understanding the pathophysiology of endometriosis is changing our diagnosis and treatment. Endometriosis lesions are clones of specific cells, with variable characteristics as aromatase activity and progesterone resistance. Therefore the GE theory postulates GE incidents to start endometriosis, which thus is different from implanted endometrium. The subsequent growth in the specific environment of the peritoneal cavity is associated with angiogenesis, inflammation, immunologic changes and bleeding in the lesions causing fibrosis. Fibrosis will stop the growth and lesions look burnt out. The pain caused by endometriosis lesions is variable: some lesions are not painful while other lesions cause neuroinflammation at distance up to 28 mm. Diagnosis of endometriosis is made by laparoscopy, following an experience guided clinical decision, based on history, symptoms, clinical exam and imaging. Biochemical markers are not useful. For deep endometriosis, imaging is important before surgery, notwithstanding rather poor predictive values when confidence limits, the prevalence of the disease and the absence of stratification of lesions by size, localization and depth of infiltration, are considered. Surgery of endometriosis is based on recognition and excision. Since the surrounding fibrosis belongs to the body with limited infiltration by endometriosis, a rim of fibrosis can be left without safety margins. For deep endometriosis, this results in a conservative excision eventually with discoid excision or short bowel resections. For cystic ovarian endometriosis superficial destruction, if complete, should be sufficient. Understanding pathophysiology is important for the discussion of early intervention during adolescence. Considering neuroinflammation at distance, the indication to explore large somatic nerves should be reconsidered. Also, medical therapy of endometriosis has to be reconsidered since the variability of lesions results in a variable response, some lesions not requiring estrogens for growth and some being progesterone resistant. If the onset of endometriosis is driven by oxidative stress from retrograde menstruation and the peritoneal microbiome, medical therapy could prevent new lesions and becomes indicated after surgery.
Topics: Biomarkers; Cytodiagnosis; Diagnostic Techniques, Endocrine; Diagnostic Techniques, Obstetrical and Gynecological; Endometriosis; Female; Humans; Laparoscopy; Pelvic Pain; Peritoneal Diseases
PubMed: 34899597
DOI: 10.3389/fendo.2021.745548 -
Taiwanese Journal of Obstetrics &... Nov 2022Endometriosis, manifested by pain and infertility, is a chronic inflammatory disease, associated with a large disability of daily living, causing a socio-economic... (Review)
Review
Endometriosis, manifested by pain and infertility, is a chronic inflammatory disease, associated with a large disability of daily living, causing a socio-economic diastrophic problem and burden. The main goal of therapy attempts to reduce pain, correct infertility and possibly avoid or delay occurrence of long-term endometriosis-associated sequelae, such as fibrosis, adhesion and malignant transformation. Although the advanced technology (minimally invasive diagnostic tools, magnetic resonance imaging, high-resolution vaginal ultrasound etc.) and the better understanding pathophysiology of endometriosis for development of new therapeutic strategy is continuous for both diagnosis and management of endometriosis, there is still presence of many debated issues, which commonly occur in routine clinical practice. For example, the timing and duration of medications may be one of most frequently discussed issues. In this part I, we would like to overview the general background knowledge (basic concept) about the endometriosis, and emphasize the role of clinical diagnosis and possible empirical medical treatment (therapeutic test) for the management of women with endometriosis.
Topics: Humans; Female; Endometriosis; Infertility, Female; Ultrasonography; Chronic Disease; Vagina; Pain
PubMed: 36427994
DOI: 10.1016/j.tjog.2022.08.002 -
Endocrine Reviews Aug 2019Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the... (Review)
Review
Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-Ī². Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
Topics: Animals; Endometriosis; Endometrium; Female; Humans; Mice; Receptors, Progesterone; Stromal Cells; Uterine Diseases
PubMed: 30994890
DOI: 10.1210/er.2018-00242 -
International Journal of Environmental... May 2022For 100 years, pelvic endometriosis has been considered to originate from the implantation of endometrial cells following retrograde menstruation or metaplasia. Since... (Review)
Review
For 100 years, pelvic endometriosis has been considered to originate from the implantation of endometrial cells following retrograde menstruation or metaplasia. Since some observations, such as the clonal aspect, the biochemical variability of lesions and endometriosis in women without endometrium, the genetic-epigenetic (G-E) theory describes that endometriosis only begins after a series of cumulative G-E cellular changes. This explains that the endometriotic may originate from any pluripotent cell apart from the endometrium, that 'endometrium-like cells' can harbour important G-E differences, and that the risk is higher in predisposed women with more inherited incidents. A consequence is a high risk after puberty which decreases progressively thereafter. Considering a 10-year delay between initiation and performing a laparoscopy, this was observed in the United Arab Emirates, Belgium, France and USA. The subsequent growth varies with the G-E changes and the environment but is self-limiting probably because of the immunologic reaction and fibrosis. That each lesion has a different set of G-E incidents explains the variability of pain and the response to hormonal treatment. New lesions may develop, but recurrences after surgical excision are rare. The fibrosis around endometriosis belongs to the body and does not need to be removed. This suggests conservative excision or minimal bowel without safety margins and superficial treatment of ovarian endometriosis. This G-E concept also suggests prevention by decreasing oxidative stress from retrograde menstruation or the peritoneal microbiome. This suggests the prevention of vaginal infections and changes in the gastrointestinal microbiota through food intake and exercise. In conclusion, a higher risk of initiating endometriosis during adolescence was observed in UAE, France, Belgium and USA. This new understanding and the limited growth opens perspectives for earlier diagnosis and better treatment.
Topics: Adolescent; Endometriosis; Endometrium; Female; Fibrosis; Humans; Menstruation Disturbances; Peritoneum
PubMed: 35682310
DOI: 10.3390/ijerph19116725 -
CMAJ : Canadian Medical Association... Mar 2023
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Journal of Medicine and Life Sep 2014Endometriosis is a debilitating disease with features of chronic inflammation. Endometriosis appears to be one of the most common benign gynecological proliferations in... (Review)
Review
Endometriosis is a debilitating disease with features of chronic inflammation. Endometriosis appears to be one of the most common benign gynecological proliferations in premenopausal women since it is estimated that 10-15% of reproductive aged women suffer from pelvic endometriosis. The biology of endometriosis is unclear. Despite its prevalence, this disease remains poorly understood and current studies prove that there is no relationship between the extent of the disease and its symptomatology. There is no blood test available for the diagnosis of endometriosis. Up to this point, there is no single very successful option for the treatment of endometriosis. Due to the relatively poor efficacy of hormonal therapy for endometriosis, several other experimental therapies are currently undergoing clinical trial.
Topics: Apoptosis; Cell Proliferation; Contraceptives, Oral, Hormonal; Dioxins; Endometriosis; Female; Humans; Menstruation; Models, Biological; Prevalence
PubMed: 25408753
DOI: No ID Found -
Journal of Assisted Reproduction and... Aug 2010Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and... (Review)
Review
Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.
Topics: Endometriosis; Female; Fertilization in Vitro; Humans; Infertility, Female
PubMed: 20574791
DOI: 10.1007/s10815-010-9436-1 -
Fertility and Sterility Feb 2019To study the pathophysiology of endometriosis. (Review)
Review
OBJECTIVE
To study the pathophysiology of endometriosis.
DESIGN
Overview of observations on endometriosis.
SETTING
Not applicable.
PATIENT(S)
None.
INTERVENTIONS(S)
None.
MAIN OUTCOME MEASURE(S)
The hypothesis is compatible with all observations.
RESULT(S)
Endometriosis, endometrium-like tissue outside the uterus, has a variable macroscopic appearance and a poorly understood natural history. It is a hereditary and heterogeneous disease with many biochemical changes in the lesions, which are clonal in origin. It is associated with pain, infertility, adenomyosis, and changes in the junctional zone, placentation, immunology, plasma, peritoneal fluid, and chronic inflammation of the peritoneal cavity. The Sampson hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread, or the metaplasia theory cannot explain all observations if metaplasia is defined as cells with reversible changes and an abnormal behavior/morphology due to the abnormal environment. We propose a polygenetic/polyepigenetic mechanism. The set of genetic and epigenetic incidents transmitted at birth could explain the hereditary aspects, the predisposition, and the endometriosis-associated changes in the endometrium, immunology, and placentation. To develop typical, cystic ovarian or deep endometriosis lesions, a variable series of additional transmissible genetic and epigenetic incidents are required to occur in a cell which may vary from endometrial to stem cells. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur. Typical cystic ovarian or deep endometriosis lesions are heterogeneous and represent three different diseases.
CONCLUSION(S)
The genetic epigenetic theory is compatible with all observations on endometriosis. Implications for treatment and prevention are discussed.
Topics: Animals; Endometriosis; Endometrium; Epigenesis, Genetic; Female; Genetic Markers; Genetic Predisposition to Disease; Heredity; Humans; Phenotype; Prognosis; Risk Factors
PubMed: 30527836
DOI: 10.1016/j.fertnstert.2018.10.013