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. (Fertil Steril Ò 2019;111:327-40. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

and recognition of subtle lesions is problematic. Reliable surgical data are small series not permitting multivariate analysis. Endometriosis is a hereditary disease. The oxidative stress of heavy menstrual bleeding with retrograde menstruation and an altered pelvic microbiome are probably associated with increasingly severe endometriosis. Whether the prevalence is increasing, or whether endometriosis is associated with fat intake or an increased risk of cardiovascular disease is unclear.

Background: To review women with symptomatic and clinically progressive endometriosis after menopause in the absence of estrogen intake or excessive systemic endogenous production.Design: Seven case reports and a systematic review of the literature from 1995 till February 2018. Results: Only 7 case reports from the authors and 29 cases from the literature described women with either cystic ovarian or deep endometriosis. Severity, symptoms, and localization are highly variable. No case report describes symptomatic superficial typical lesions. In 22 of 36 women (61%), symptoms started more than 10 years after menopause. Conclusions: Symptomatic and clinically progressive endometriosis after menopause in the absence of increased systemic estrogen concentrations or exogenous estrogen intake starts more than 10 years after menopause in the majority of women. This observation suggests that a genetic and/or epigenetic incident caused estrogen-independent progression, increased sensitivity to estrogens or increased local production of estrogens. This observation is important for understanding the pathophysiology of endometriosis, for the management of postmenopausal endometriosis, and for individualization of medical therapy of endometriosis since estrogen-independent endometriosis growth probably also occurs before menopause.