Materiały źródłowe

• #1 Adenomyosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539868/

  Adenomyosis is a gynecologic condition characterized by ectopic endometrial tissue within the uterine myometrium. […] While the histology is well-described, the etiology of adenomyosis is not known definitively. Researchers have postulated several theories. The most commonly accepted theory is that adenomyosis results from a disrupted boundary between the deepest layer of the endometrium (endometrium basalis) and the underlying myometrium. This process leads to a cycle of inappropriate endometrial proliferation into the myometrium with subsequent small vessel angiogenesis as well as adjacent myometrial smooth muscle hypertrophy and hyperplasia. Data demonstrating a higher prevalence of adenomyosis following dilation and curettage and cesarean section support this theory. […] A second theory proposes an embryologic mechanism whereby pluripotent Mullerian stem cells undergo inappropriate differentiation leading to ectopic endometrial tissue. This theory has support from evidence demonstrating altered expression of specific genetic markers, in addition to case reports of endometrial tissue found in women with Rokitansky-Kuster-Hauser syndrome (Mullerian agenesis). […] Other less well-accepted theories propose altered lymphatic drainage pathways and displaced bone marrow stem cells to explain the presence of ectopic endometrial tissue.

• #2 Adenomyosis – Wikipedia

  https://en.wikipedia.org/wiki/Adenomyosis

  Adenomyosis can be found together with endometriosis; it differs in that patients with endometriosis present endometrial-like tissue located entirely outside the uterus. […] The cause of adenomyosis can be associated with Caesarean births, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, known as the junctional zone, such as a caesarean section, surgical pregnancy termination, and any pregnancy. […] The pathogenesis of adenomyosis still remains unclear, but the functioning of the inner myometrium, also called the junction zone (JZ), is believed to play a major role in the development of adenomyosis. […] Parity, age, and previous uterine abrasion increase the risk of adenomyosis. […] Hormonal factors such as local hyperestrogenism and elevated levels of s-prolactin as well as autoimmune factors have also been identified as possible risk factors.

• #3 Adenomyosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adenomyosis/symptoms-causes/syc-20369138

  Doctors aren’t sure what causes adenomyosis, but the disease usually resolves after menopause. […] The cause of adenomyosis isn’t known. There have been many theories, including: […] Some experts believe that endometrial cells from the lining of the uterus invade the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) might promote the direct invasion of the endometrial cells into the wall of the uterus. […] Other experts suspect that endometrial tissue is deposited in the uterine muscle when the uterus is first formed in the fetus. […] Another theory suggests a link between adenomyosis and childbirth. Inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of cells that line the uterus. […] A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis. […] Regardless of how adenomyosis develops, its growth depends on the body’s circulating estrogen.

• #4 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

• #5 Adenomyosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539868/

  Adenomyosis is a gynecologic condition characterized by ectopic endometrial tissue within the uterine myometrium. […] While the histology is well-described, the etiology of adenomyosis is not known definitively. Researchers have postulated several theories. The most commonly accepted theory is that adenomyosis results from a disrupted boundary between the deepest layer of the endometrium (endometrium basalis) and the underlying myometrium. This process leads to a cycle of inappropriate endometrial proliferation into the myometrium with subsequent small vessel angiogenesis as well as adjacent myometrial smooth muscle hypertrophy and hyperplasia. Data demonstrating a higher prevalence of adenomyosis following dilation and curettage and cesarean section support this theory. […] A second theory proposes an embryologic mechanism whereby pluripotent Mullerian stem cells undergo inappropriate differentiation leading to ectopic endometrial tissue. This theory has support from evidence demonstrating altered expression of specific genetic markers, in addition to case reports of endometrial tissue found in women with Rokitansky-Kuster-Hauser syndrome (Mullerian agenesis). […] Other less well-accepted theories propose altered lymphatic drainage pathways and displaced bone marrow stem cells to explain the presence of ectopic endometrial tissue.

• #6 Adenomyosis: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2022/0100/p33.html

  Adenomyosis is a clinical condition where endometrial glands are found in the myometrium of the uterus. […] Risk factors for developing adenomyosis include increasing age, parity, and history of uterine procedures. […] Two theories prevail regarding the pathogenesis of adenomyosis. The first theory suggests that with injury of the endometrium, the basalis endometrium invaginates into the myometrium through an altered or interrupted junctional zone creating adenomyotic lesions. The tissue injury and repair theory may help explain why having a previous uterine procedure (e.g., cesarean delivery, dilation and curettage) increases the risk of subsequent adenomyosis. The second theory suggests that adenomyotic lesions arise from metaplasia of embryonic pluripotent Mllerian remnants. […] Common signs of adenomyosis include uterine enlargement, uterine tenderness with boggy consistency, and infertility. […] Impaired fertility in adenomyosis is thought to be attributable to abnormal thickening of the junctional zone of the myometrium, abnormal uterine peristalsis, and altered sperm transport.

• #7 Adenomyosis – Wikipedia

  https://en.wikipedia.org/wiki/Adenomyosis

  Adenomyosis can be found together with endometriosis; it differs in that patients with endometriosis present endometrial-like tissue located entirely outside the uterus. […] The cause of adenomyosis can be associated with Caesarean births, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, known as the junctional zone, such as a caesarean section, surgical pregnancy termination, and any pregnancy. […] The pathogenesis of adenomyosis still remains unclear, but the functioning of the inner myometrium, also called the junction zone (JZ), is believed to play a major role in the development of adenomyosis. […] Parity, age, and previous uterine abrasion increase the risk of adenomyosis. […] Hormonal factors such as local hyperestrogenism and elevated levels of s-prolactin as well as autoimmune factors have also been identified as possible risk factors.

• #8 Adenomyosis – Wikipedia

  https://en.wikipedia.org/wiki/Adenomyosis

  A complex origin that includes multifactorial changes on both genetic and biochemical levels is likely. […] The tissue injury and repair (TIAR) theory is now widely accepted and suggests that uterine hyperperistalsis (i.e., increased peristalsis), during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface (EMI) region. […] That again leads to elevation of local estrogen in order to heal the damage. […] At the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. […] Iatrogenic injury of the junctional zone or physical damage due to placental implantation most likely results in the same pathological cascade.

• #9

  https://link.springer.com/article/10.1007/s13669-022-00326-7

  Adenomyosis pathogenesis is still a topic under investigation, however advancements in the understanding of disease development and mechanisms have been made. […] So far, three theories for the pathophysiology of adenomyosis have been proposed: 1. An invagination of the endometrial basalis into the myometrium by tissue injury and repair. 2. The development from adult stem cells or displaced embryonic mullerian remnants. 3. An invasion from outside to inside. […] In order to invade and develop, endometrial cells require a series of pathogenetic mechanisms which drive to adenomyosis. Altered sex steroids hormones receptors may be the primary event which causes increased endometrial cell proliferations and differentiation from epithelial to mesenchymal cells. […] In order to explain the migration of endometrial cells and development of adenomyotic lesions within the myometrium, at least three theories are currently debated: a invasion from inside, b metaplasia of displaced embryonic pluripotent Mullerian remnants or adult stem cells, or c invasion from outside.

• #10 Adenomyosis – Wikipedia

  https://en.wikipedia.org/wiki/Adenomyosis

  A complex origin that includes multifactorial changes on both genetic and biochemical levels is likely. […] The tissue injury and repair (TIAR) theory is now widely accepted and suggests that uterine hyperperistalsis (i.e., increased peristalsis), during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface (EMI) region. […] That again leads to elevation of local estrogen in order to heal the damage. […] At the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. […] Iatrogenic injury of the junctional zone or physical damage due to placental implantation most likely results in the same pathological cascade.

• #11 Adenomyosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539868/

  Adenomyosis is a gynecologic condition characterized by ectopic endometrial tissue within the uterine myometrium. […] While the histology is well-described, the etiology of adenomyosis is not known definitively. Researchers have postulated several theories. The most commonly accepted theory is that adenomyosis results from a disrupted boundary between the deepest layer of the endometrium (endometrium basalis) and the underlying myometrium. This process leads to a cycle of inappropriate endometrial proliferation into the myometrium with subsequent small vessel angiogenesis as well as adjacent myometrial smooth muscle hypertrophy and hyperplasia. Data demonstrating a higher prevalence of adenomyosis following dilation and curettage and cesarean section support this theory. […] A second theory proposes an embryologic mechanism whereby pluripotent Mullerian stem cells undergo inappropriate differentiation leading to ectopic endometrial tissue. This theory has support from evidence demonstrating altered expression of specific genetic markers, in addition to case reports of endometrial tissue found in women with Rokitansky-Kuster-Hauser syndrome (Mullerian agenesis). […] Other less well-accepted theories propose altered lymphatic drainage pathways and displaced bone marrow stem cells to explain the presence of ectopic endometrial tissue.

• #12 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  The invagination theory of adenomyosis development has been proposed to result from altered endometrial basalis cells or cell groups invading into the myometrium, crossing an injured or abnormal junctional zone, and subsequently establishing ectopic adenomyotic lesions and inducing hypotrophy and dysfunction of myocytes in the IM and OM. In support of this hypothesis are the clinical observations that adenomyosis risk increases with repeated sharp endometrial curettage, cesarean delivery, and prior uterine surgery wherein the EMI is breached. […] It has been postulated that during Mullerian duct development and fusion, some remnants of the embryonic tissue may be misplaced in the myometrium, subsequently giving rise in adult women to adenomyosis. Thus, embryonic Mullerian remnants may undergo metaplastic changes in adult myometrium, leading to establishing de novo ectopic endometrial tissue.

• #13 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  The invagination theory of adenomyosis development has been proposed to result from altered endometrial basalis cells or cell groups invading into the myometrium, crossing an injured or abnormal junctional zone, and subsequently establishing ectopic adenomyotic lesions and inducing hypotrophy and dysfunction of myocytes in the IM and OM. In support of this hypothesis are the clinical observations that adenomyosis risk increases with repeated sharp endometrial curettage, cesarean delivery, and prior uterine surgery wherein the EMI is breached. […] It has been postulated that during Mullerian duct development and fusion, some remnants of the embryonic tissue may be misplaced in the myometrium, subsequently giving rise in adult women to adenomyosis. Thus, embryonic Mullerian remnants may undergo metaplastic changes in adult myometrium, leading to establishing de novo ectopic endometrial tissue.

• #14 Adenomyosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adenomyosis/symptoms-causes/syc-20369138

  Doctors aren’t sure what causes adenomyosis, but the disease usually resolves after menopause. […] The cause of adenomyosis isn’t known. There have been many theories, including: […] Some experts believe that endometrial cells from the lining of the uterus invade the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) might promote the direct invasion of the endometrial cells into the wall of the uterus. […] Other experts suspect that endometrial tissue is deposited in the uterine muscle when the uterus is first formed in the fetus. […] Another theory suggests a link between adenomyosis and childbirth. Inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of cells that line the uterus. […] A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis. […] Regardless of how adenomyosis develops, its growth depends on the body’s circulating estrogen.

• #15 Adenomyosis: Symptoms, Causes, and Treatments

  https://www.webmd.com/women/adenomyosis-symptoms-causes-treatments

  Doctors don’t know what causes this condition, but they have some theories: […] Cells from your uterine lining might invade the muscle wall. If you have surgery on your uterus, such as a C-section, that might provide an opening for cells to spread. […] Some cells might grow in the wrong place during fetal development, meaning you’re born with the misplaced tissue already in the muscle wall. […] The uterine lining can get inflamed after childbirth, which might cause a breakdown in the barrier between the lining and the muscle wall. […] Bone marrow stem cells, which are cells that have the ability to develop into other cell types, may play a role in the development of the abnormal tissue, some researchers believe.

• #16 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  In addition to invasion of stem cells from endometrial basalis directly into the myometrium, retrograde menstruation may also result in deposition of adult stem cells into the myometrium. […] Genetic variants involving key processes in adenomyosis development include steroid hormone function, ECM dysregulation, angiogenesis, TIAR, and inflammation. […] Abnormal genetic and epigenetic factors result in the hyperestrogenism and progesterone resistance, promoting cell proliferation, migration, EMT, and invasiveness of endometrial cellular components into the myometrial compartment. […] That adenomyosis as an estrogen-dependent disease is based on multiple observations. For example, in a mouse model, prolonged treatment with estrogen results in inducing adenomyosis. In women, elevated E2 levels in menstrual blood of those with adenomyosis without concomitant elevations in peripheral blood, compared with controls, suggest that local rather than systemic hyperestrogenism contributes to the development of the disease.

• #17 Adenomyosis | Bucharest Endometriosis Center | Dr. Gabriel Mitroi

  https://bucharestendometriosiscenter.com/adenomyosis/

  Cell migration at the myometrium level due to hyperexpression of estrogen receptors or that there may be intra-myometrium lymphatic migration of aberrant endometrial stem cells. […] Some studies mention uterus surgeries as a risk factor. Although the cause of adenomyosis is not completely elucidated, it seems that hormones (estrogen, progesterone, FSH, prolactin, etc.) act as a trigger for the disease. Etiology, as with endometriosis, is a genetic one.

• #18 Adenomyosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adenomyosis/symptoms-causes/syc-20369138

  Doctors aren’t sure what causes adenomyosis, but the disease usually resolves after menopause. […] The cause of adenomyosis isn’t known. There have been many theories, including: […] Some experts believe that endometrial cells from the lining of the uterus invade the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) might promote the direct invasion of the endometrial cells into the wall of the uterus. […] Other experts suspect that endometrial tissue is deposited in the uterine muscle when the uterus is first formed in the fetus. […] Another theory suggests a link between adenomyosis and childbirth. Inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of cells that line the uterus. […] A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis. […] Regardless of how adenomyosis develops, its growth depends on the body’s circulating estrogen.

• #19 Adenomyosis: Symptoms and Treatment | Dr. Thais Aliabadi, Los Angeles

  https://www.draliabadi.com/gynecology/conditions-of-the-uterus/adenomyosis/

  Adenomyosis is a condition in which the endometrial tissue that lines the uterus grows into the muscular walls of the uterus. […] The exact cause of adenomyosis remains unknown. Adenomyosis risk factors include: […] Even though the cause of adenomyosis isn’t known, there have been many theories, including: […] Adenomyosis could result from the direct invasion of endometrial cells from the lining of the uterus into the muscle of the uterine walls. […] Adenomyosis may start within the uterine muscle from endometrial tissue deposited there when the uterus first formed in the fetus. […] Inflammation of the lining of the uterus during the postpartum period might cause a break in the normal boundary of cells that line the uterus, allowing endometrial cells to invade the uterine wall. […] A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis. […] Regardless of how adenomyosis develops, its growth depends on the circulating estrogen in women’s bodies.

• #20 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  In addition to invasion of stem cells from endometrial basalis directly into the myometrium, retrograde menstruation may also result in deposition of adult stem cells into the myometrium. […] Genetic variants involving key processes in adenomyosis development include steroid hormone function, ECM dysregulation, angiogenesis, TIAR, and inflammation. […] Abnormal genetic and epigenetic factors result in the hyperestrogenism and progesterone resistance, promoting cell proliferation, migration, EMT, and invasiveness of endometrial cellular components into the myometrial compartment. […] That adenomyosis as an estrogen-dependent disease is based on multiple observations. For example, in a mouse model, prolonged treatment with estrogen results in inducing adenomyosis. In women, elevated E2 levels in menstrual blood of those with adenomyosis without concomitant elevations in peripheral blood, compared with controls, suggest that local rather than systemic hyperestrogenism contributes to the development of the disease.

• #21 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  In addition to invasion of stem cells from endometrial basalis directly into the myometrium, retrograde menstruation may also result in deposition of adult stem cells into the myometrium. […] Genetic variants involving key processes in adenomyosis development include steroid hormone function, ECM dysregulation, angiogenesis, TIAR, and inflammation. […] Abnormal genetic and epigenetic factors result in the hyperestrogenism and progesterone resistance, promoting cell proliferation, migration, EMT, and invasiveness of endometrial cellular components into the myometrial compartment. […] That adenomyosis as an estrogen-dependent disease is based on multiple observations. For example, in a mouse model, prolonged treatment with estrogen results in inducing adenomyosis. In women, elevated E2 levels in menstrual blood of those with adenomyosis without concomitant elevations in peripheral blood, compared with controls, suggest that local rather than systemic hyperestrogenism contributes to the development of the disease.

• #22

  https://link.springer.com/article/10.1007/s13669-022-00326-7

  Several mechanisms are involved in the pathogenesis of adenomyosis: impaired gonadal sex steroids hormones receptors function, altered cell proliferation and differentiation, inflammatory reaction, processes of neuroangiogenesis and fibrosis. […] Adenomyosis is promoted by an imbalance between estrogens and progesterone signaling in women during reproductive life. […] The imbalance between estrogens and progesterone signaling is also caused by a decrease of progesterone activity, as suggested by the evidence that stromal cells of the functionalis and basalis endometrium of women with adenomyosis display a reduced immunoreactivity for isoform B of P receptor (PR-B), causing a loss of P effects. […] In addition, in ectopic endometrium, all three DNA Methyltransferases (DNMTs) are abnormally expressed, causing epigenetic changes.

• #23 Uterine Adenomyosis > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/uterine-adenomyosis

  Uterine adenomyosis is a condition in which the lining of the uterus grows into the walls of the uterus. […] Doctors aren’t sure exactly what causes uterine adenomyosis. However, evidence suggests that prolonged exposure to estrogen may be a contributing factor. […] Exposure to other hormones, including progesterone, prolactin, and follicle-stimulating hormone (FSH), and/or a history of uterine surgery, may also lead to the condition.

• #24 Adenomyosis – Symptoms, Causes, Diagnosis & Treatment

  https://drseckin.com/adenomyosis/

  What causes adenomyosis? […] In the last decade, an increasing number of studies have identified various causes for adenomyosis. These include sex hormone receptors, inflammatory molecules, extracellular matrix enzymes, growth factors, and neuroangiogenic factors. […] There are many theories surrounding adenomyosis that continue to evolve. Below is a summary of current theories: […] Prior uterine surgery or childbirth causes inflammation of the uterine lining that might cause a break in the healthy boundary of cells lining the uterus. Surgical procedures on the uterus can have a similar effect. […] Tissue trauma or any vaginal injury that allows inflammation can lead to macrophages and cytokines migrating into the myometrium. […] High expression of estrogen receptors can stimulate migratory tissue into the myometrium. […] Myometrium cells can spread and build up through the lymphatic system or through stem cells. […] Various hormones including estrogen, progesterone, prolactin, and the follicle-stimulating hormone may trigger the condition.

• #25

  https://link.springer.com/article/10.1007/s13669-022-00326-7

  Several mechanisms are involved in the pathogenesis of adenomyosis: impaired gonadal sex steroids hormones receptors function, altered cell proliferation and differentiation, inflammatory reaction, processes of neuroangiogenesis and fibrosis. […] Adenomyosis is promoted by an imbalance between estrogens and progesterone signaling in women during reproductive life. […] The imbalance between estrogens and progesterone signaling is also caused by a decrease of progesterone activity, as suggested by the evidence that stromal cells of the functionalis and basalis endometrium of women with adenomyosis display a reduced immunoreactivity for isoform B of P receptor (PR-B), causing a loss of P effects. […] In addition, in ectopic endometrium, all three DNA Methyltransferases (DNMTs) are abnormally expressed, causing epigenetic changes.

• #26

  https://link.springer.com/article/10.1007/s13669-022-00326-7

  Findings from this study suggest that Kras, a cancer-associated gene, plays a role in the pathogenesis of adenomyosis. […] The development of adenomyosis is related to the endometrial cells invasiveness of myometrium, and the epithelial-to-mesenchymal transition (EMT) is the one of the most accepted mechanism to support the changes undergoing ectopic endometrial cells. […] Nowadays, adenomyosis is considered as a chronic inflammatory disease characterized by abundant inflammatory mediators both into adenomyotic lesions and in the peritoneal fluid. […] Fibrosis is another mechanism involved in the pathogenesis of adenomyosis.

• #27 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  In addition to invasion of stem cells from endometrial basalis directly into the myometrium, retrograde menstruation may also result in deposition of adult stem cells into the myometrium. […] Genetic variants involving key processes in adenomyosis development include steroid hormone function, ECM dysregulation, angiogenesis, TIAR, and inflammation. […] Abnormal genetic and epigenetic factors result in the hyperestrogenism and progesterone resistance, promoting cell proliferation, migration, EMT, and invasiveness of endometrial cellular components into the myometrial compartment. […] That adenomyosis as an estrogen-dependent disease is based on multiple observations. For example, in a mouse model, prolonged treatment with estrogen results in inducing adenomyosis. In women, elevated E2 levels in menstrual blood of those with adenomyosis without concomitant elevations in peripheral blood, compared with controls, suggest that local rather than systemic hyperestrogenism contributes to the development of the disease.

• #28 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  In addition to invasion of stem cells from endometrial basalis directly into the myometrium, retrograde menstruation may also result in deposition of adult stem cells into the myometrium. […] Genetic variants involving key processes in adenomyosis development include steroid hormone function, ECM dysregulation, angiogenesis, TIAR, and inflammation. […] Abnormal genetic and epigenetic factors result in the hyperestrogenism and progesterone resistance, promoting cell proliferation, migration, EMT, and invasiveness of endometrial cellular components into the myometrial compartment. […] That adenomyosis as an estrogen-dependent disease is based on multiple observations. For example, in a mouse model, prolonged treatment with estrogen results in inducing adenomyosis. In women, elevated E2 levels in menstrual blood of those with adenomyosis without concomitant elevations in peripheral blood, compared with controls, suggest that local rather than systemic hyperestrogenism contributes to the development of the disease.

• #29 Adenomyosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2500101-overview

  Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. […] Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades, likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development. […] Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. […] There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. […] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated.

• #30 Adenomyosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2500101-overview

  Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. […] Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades, likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development. […] Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. […] There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. […] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated.

• #31 Adenomyosis

  https://www.nhs.uk/conditions/adenomyosis/

  Adenomyosis is a condition where the lining of the womb (uterus) starts growing into the muscle in the wall of the womb. […] It’s not clear what causes adenomyosis. […] You may be more likely to get it if you are over the age of 30 and have given birth.

• #32 Adenomyosis Causes, Symptoms, and Treatments

  https://www.upmc.com/services/womens-health/conditions/adenomyosis

  What causes adenomyosis? Doctors are still trying to learn more about this condition, but believe some factors are linked to uterine adenomyosis. They may be: Injury to or inflammation of the uterus. Prolonged exposure to estrogen. Exposure to progesterone or prolactin. History of uterine surgery. […] Currently, researchers aren’t certain how the cells lining the uterus enter the muscles. The condition usually goes away after menopause.

• #33 Adenomyosis: Causes, Diagnosis and Therapy – Endometriose

  https://endometriose.app/en/adenomyosis-causes-diagnosis-and-therapy-as-well-as-differentiation-from-endometriosis/

  A recent theory proposes that strong uterine contractions may cause micro-tears in the layer separating the mucosa from the muscle. These injuries subsequently stimulate an increased release of estrogen and permit the infiltration of cells into the muscular layer. This phenomenon, referred to as tissue-injury-and-repair (TIAR), is recognized in adenomyosis but, like other theories, has yet to be definitively proven. […] Several risk factors have been associated with the development of adenomyosis, including uterine surgeries, multiple pregnancies, advanced age, early onset of first menstruation (at age 10 or younger), short menstrual cycles (24 days or less), and obesity.

• #34 Adenomyosis of the Uterus: Symptoms, Treatment & Endometriosis Link

  https://www.emedicinehealth.com/adenomyosis_uterus/article_em.htm

  Adenomyosis causes heavy, painful menstrual periods. […] The cause of adenomyosis is unknown but some causes may include: Hormones, Bone marrow stem cells entering the uterine muscle, Inflammation of the uterus following childbirth. […] Risk factors for adenomyosis include: Childbirth, Early age of menstrual onset, Short menstrual cycles, Previous uterine surgeries, Cesarean section, Removal of uterine fibroids (myomectomy), Middle age. […] Women with adenomyosis may be at higher risk of developing endometrial and thyroid cancers. […] It is believed the severe inflammation caused by adenomyosis may inhibit implantation of an embryo into the uterine lining, preventing pregnancy from occurring.

• #35 Adenomyosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2500101-overview

  Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. […] Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades, likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development. […] Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. […] There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. […] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated.

• #36 Adenomyosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2500101-overview

  Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. […] Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades, likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development. […] Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. […] There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. […] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated.

• #37 Adenomyosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adenomyosis/symptoms-causes/syc-20369138

  Doctors aren’t sure what causes adenomyosis, but the disease usually resolves after menopause. […] The cause of adenomyosis isn’t known. There have been many theories, including: […] Some experts believe that endometrial cells from the lining of the uterus invade the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) might promote the direct invasion of the endometrial cells into the wall of the uterus. […] Other experts suspect that endometrial tissue is deposited in the uterine muscle when the uterus is first formed in the fetus. […] Another theory suggests a link between adenomyosis and childbirth. Inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of cells that line the uterus. […] A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis. […] Regardless of how adenomyosis develops, its growth depends on the body’s circulating estrogen.

• #38 Adenomyosis: Symptoms, Causes, and Treatments

  https://www.webmd.com/women/adenomyosis-symptoms-causes-treatments

  Doctors don’t know what causes this condition, but they have some theories: […] Cells from your uterine lining might invade the muscle wall. If you have surgery on your uterus, such as a C-section, that might provide an opening for cells to spread. […] Some cells might grow in the wrong place during fetal development, meaning you’re born with the misplaced tissue already in the muscle wall. […] The uterine lining can get inflamed after childbirth, which might cause a breakdown in the barrier between the lining and the muscle wall. […] Bone marrow stem cells, which are cells that have the ability to develop into other cell types, may play a role in the development of the abnormal tissue, some researchers believe.

• #39 Adenomyosis causes pain, heavy periods and infertility but you’ve probably never heard of it

  https://theconversation.com/adenomyosis-causes-pain-heavy-periods-and-infertility-but-youve-probably-never-heard-of-it-104412

  Adenomyosis can have a number of causes though none have been definitively identified. […] There is an association between the presence of adenomyosis and the number of times a women has given birth: the more pregnancies, the more likely you are to have adenomyosis. […] Women with adenomyosis have also often had a trauma to the uterus such as surgery in the uterus, like during a caesarean section. […] There is some evidence adenomyosis can reduce fertility, but this is still controversial. […] Some MRI studies show changes consistent with infertility, but because patients presenting with infertility in their 30s and 40s are more likely to be diagnosed with adenomyosis, its difficult to say if adenomyosis is the cause of their fertility issues.

• #40 Adenomyosis Risk Factors | Adenomyosis Causes and Symptoms

  https://azgyn.com/blog/adenomyosis-symptoms-causes-and-risk-factors/

  Adenomyosis is a condition in which the endometrium, instead of growing out into the uterus, grows into the uterine wall (myometrium). […] Middle-aged women who already have had children (the more children, the greater the risk) or who have had uterine surgery, such as a cesarean, or an inflammation after childbirth are more at risk for adenomyosis, however it can affect any woman before menopause. […] The causes are mostly unknown, however women who have had uterine surgery or trauma, are more at risk than others.

• #41 Adenomyosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2500101-overview

  Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. […] Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades, likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development. […] Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. […] There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. […] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated.

• #42 Adenomyosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2500101-overview

  Adenomyosis has been most strongly associated with middle age, multiparous status, and a history of gynecologic surgery. […] Adenomyosis is most frequently diagnosed in women in their fourth and fifth decades, likely because of the increased prevalence of risk factors by that age range and the duration of adenomyotic development. […] Increased parity is thought to have a significant role in the development of adenomyosis. Pregnancy may mechanically disrupt the myometrial junctional zone by the action of the trophoblast on the myometrium, favoring infiltration of endometrial cells into the myometrium. […] There is much rationale surrounding the notion that gynecologic surgery may precipitate adenomyosis. In theory, any kind of uterine surgery is thought to mechanically traumatize the uterus. This may cause weaknesses within the myometrium, allowing invasion of the adjacent endometrium. […] Women with a history of multiple curettage procedures have a well-documented increased risk of adenomyosis; however, the risk associated with cesarean section and other uterine procedures is still debated.

• #43 Adenomyosis of the Uterus: Symptoms, Treatment & Endometriosis Link

  https://www.emedicinehealth.com/adenomyosis_uterus/article_em.htm

  Adenomyosis causes heavy, painful menstrual periods. […] The cause of adenomyosis is unknown but some causes may include: Hormones, Bone marrow stem cells entering the uterine muscle, Inflammation of the uterus following childbirth. […] Risk factors for adenomyosis include: Childbirth, Early age of menstrual onset, Short menstrual cycles, Previous uterine surgeries, Cesarean section, Removal of uterine fibroids (myomectomy), Middle age. […] Women with adenomyosis may be at higher risk of developing endometrial and thyroid cancers. […] It is believed the severe inflammation caused by adenomyosis may inhibit implantation of an embryo into the uterine lining, preventing pregnancy from occurring.

• #44 Adenomyosis – Wikipedia

  https://en.wikipedia.org/wiki/Adenomyosis

  A complex origin that includes multifactorial changes on both genetic and biochemical levels is likely. […] The tissue injury and repair (TIAR) theory is now widely accepted and suggests that uterine hyperperistalsis (i.e., increased peristalsis), during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface (EMI) region. […] That again leads to elevation of local estrogen in order to heal the damage. […] At the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. […] Iatrogenic injury of the junctional zone or physical damage due to placental implantation most likely results in the same pathological cascade.

• #45

  https://link.springer.com/article/10.1007/s13669-022-00326-7

  Findings from this study suggest that Kras, a cancer-associated gene, plays a role in the pathogenesis of adenomyosis. […] The development of adenomyosis is related to the endometrial cells invasiveness of myometrium, and the epithelial-to-mesenchymal transition (EMT) is the one of the most accepted mechanism to support the changes undergoing ectopic endometrial cells. […] Nowadays, adenomyosis is considered as a chronic inflammatory disease characterized by abundant inflammatory mediators both into adenomyotic lesions and in the peritoneal fluid. […] Fibrosis is another mechanism involved in the pathogenesis of adenomyosis.

• #46 Adenomyosis: What it is and how it affects fertility | IVF-Life

  https://www.ivf-spain.com/en/blog/adenomyosis-a-possible-cause-of-infertility-in-women

  Adenomyosis or uterine adenomyosis is a fairly common condition. It is characterized by the presence of endometrial tissue (the lining of the uterus) within the myometrium, the muscular layer of the uterus. […] The exact cause of adenomyosis is not precisely known, although it is believed to be due to a combination of hormonal, surgical, genetic, and inflammatory factors. […] Estrogens, for example, which are female sex hormones, play an important role in adenomyosis. Elevated levels of estrogen can stimulate the growth of endometrial tissue within the uterine muscle. […] Age could be another factor that plays a role in the onset of adenomyosis, which is more common in middle-aged women, especially those who have already had several children. […] On the other hand, chronic inflammation of the uterus, caused by infections or alterations in the immune system, may also be linked to adenomyosis, as well as other genetic factors: there could be a genetic predisposition to develop adenomyosis, as it may occur more frequently in women who have close relatives with this condition. […] This uterine condition can lead to fertility problems in women, hindering the embryo implantation process and being the cause of recurrent implantation failures. Several studies indicate that up to 22% of women who have difficulty conceiving suffer from adenomyosis.

• #47 Adenomyosis – Symptoms, Causes, Diagnosis & Treatment

  https://drseckin.com/adenomyosis/

  What causes adenomyosis? […] In the last decade, an increasing number of studies have identified various causes for adenomyosis. These include sex hormone receptors, inflammatory molecules, extracellular matrix enzymes, growth factors, and neuroangiogenic factors. […] There are many theories surrounding adenomyosis that continue to evolve. Below is a summary of current theories: […] Prior uterine surgery or childbirth causes inflammation of the uterine lining that might cause a break in the healthy boundary of cells lining the uterus. Surgical procedures on the uterus can have a similar effect. […] Tissue trauma or any vaginal injury that allows inflammation can lead to macrophages and cytokines migrating into the myometrium. […] High expression of estrogen receptors can stimulate migratory tissue into the myometrium. […] Myometrium cells can spread and build up through the lymphatic system or through stem cells. […] Various hormones including estrogen, progesterone, prolactin, and the follicle-stimulating hormone may trigger the condition.

• #48 Adenomyosis : Causes, Symptoms, and Treatment

  https://www.artfertilityclinics.com/in/en/art-blog/adenomyosis-causes-symptoms-treatment

  Adenomyosis, a condition impacting the walls of the uterus, poses unique challenges for individuals. The precise causes of adenomyosis are unclear, but hormonal influences and uterine trauma are implicated. […] Understanding the causes of adenomyosis is pivotal for individuals and healthcare providers alike. The causes are: Immune System Dysfunction: An immune system that does not function optimally may be associated with the development of adenomyosis. A compromised immune response might fail to regulate the invasion of endometrial tissue into the muscular layers of the uterus. […] Hormonal Influences: Fluctuations in hormonal levels, such as elevated oestrogen, are associated with the development of adenomyosis. This hormonal imbalance may encourage the invasion of endometrial tissue into the uterine muscle. […] Inflammation: Chronic inflammation within the uterine walls may facilitate the development of adenomyosis. Inflammatory processes can alter the tissue environment and encourage the infiltration of endometrial cells.

• #49 Adenomyosis causes pain, heavy periods and infertility but you’ve probably never heard of it

  https://theconversation.com/adenomyosis-causes-pain-heavy-periods-and-infertility-but-youve-probably-never-heard-of-it-104412

  Adenomyosis can have a number of causes though none have been definitively identified. […] There is an association between the presence of adenomyosis and the number of times a women has given birth: the more pregnancies, the more likely you are to have adenomyosis. […] Women with adenomyosis have also often had a trauma to the uterus such as surgery in the uterus, like during a caesarean section. […] There is some evidence adenomyosis can reduce fertility, but this is still controversial. […] Some MRI studies show changes consistent with infertility, but because patients presenting with infertility in their 30s and 40s are more likely to be diagnosed with adenomyosis, its difficult to say if adenomyosis is the cause of their fertility issues.

• #50 What You Need To Know About Adenomyosis | EndoFound

  https://www.endofound.org/what-you-need-to-know-about-adenomyosis

  Adenomyosis is a common, often painful condition where cells from the inner lining of the uterus (the endometrium) infiltrate the muscular layer of the uterus (the myometrium). […] Some experts believe that adenomyosis occurs in uteruses that have experienced muscle trauma, such as a cesarian (C-section), which would allow endometrial tissue to migrate to the muscle wall. […] There is no known cause or cure for adenomyosis, besides having a hysterectomy. […] A 2005 study found that 79% of women with fertility issues had both endometriosis and adenomyosis; the similarity between the two conditions in terms of symptoms often makes it difficult to determine the root cause. […] Endometriosis and adenomyosis often appear together, but there is currently no evidence to suggest that either condition causes the other.

• #51 What You Need To Know About Adenomyosis | EndoFound

  https://www.endofound.org/what-you-need-to-know-about-adenomyosis

  Adenomyosis is a common, often painful condition where cells from the inner lining of the uterus (the endometrium) infiltrate the muscular layer of the uterus (the myometrium). […] Some experts believe that adenomyosis occurs in uteruses that have experienced muscle trauma, such as a cesarian (C-section), which would allow endometrial tissue to migrate to the muscle wall. […] There is no known cause or cure for adenomyosis, besides having a hysterectomy. […] A 2005 study found that 79% of women with fertility issues had both endometriosis and adenomyosis; the similarity between the two conditions in terms of symptoms often makes it difficult to determine the root cause. […] Endometriosis and adenomyosis often appear together, but there is currently no evidence to suggest that either condition causes the other.

• #52 Adenomyosis: From symptoms to treatment — Nuffield Department of Women’s & Reproductive Health

  https://www.wrh.ox.ac.uk/news/adenomyosis-from-symptoms-to-treatment

  What causes adenomyosis? […] In people with adenomyosis, endometrium-like cells are found in the wrong place the myometrium. […] Although a large number of women with adenomyosis have endometriosis as well, adenomyosis is a distinct disease from endometriosis. […] Although we know that around 20% of women having hysterectomies for reasons other than suspected adenomyosis are found to have evidence of the condition on pathology assessment.

• #53 Adenomyosis | GLOWM

  https://www.glowm.com/section-view/heading/Adenomyosis/item/601

  The relationship between the two endometrial disorders adenomyosis and endometriosis seems to have gone in a full circle. […] Adenomyosis and endometriosis may be related to an aberrant angiogenesis in the myometrial JZ. […] It seems therefore that ectopic endometrium produces estrogens; this has important consequences for both medical and surgical treatment because it tends to support the view that, to minimize the risk of recurrence in severe disease, a complete excision is mandatory and the reality is that, today, whether in severe endometriosis or in uterine adenomyosis, complete excision cannot be guaranteed.

• #54 Adenomyosis | Northern Beaches Interventional Radiology

  https://www.nbir.com.au/adenomyosis

  We dont know for sure. We know there is some link to endometriosis, a condition where cells from the lining of the womb are found outside the uterus. Adenomyosis often co-exists with fibroids, adenomyosis is routinely misdiagnosed as fibroids. […] Despite this, some experts have developed a number of theories for what might cause adenomyosis: […] Tissue growth – some experts believe that endometrial cells, from the lining of the uterus, invade the muscle of the uterine walls. […] During development – some experts believe endometrial tissues ends up in the uterine muscle when the fetus is first formed. […] Childbirth – other experts believe a link exists between adenomyosis and childbirth, where inflammation of the uterine lining during postpartum periods can break the normal boundary of the cells that line the uterus. […] Stem cells – a recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis.

• #55 What Causes Adenomyosis?

  https://www.drtan.co.nz/resources/general-gynaecology/what-causes-adenomyosis/

  Adenomyosis is a medical condition when the cells lining the inside of the uterus (endometrial cells) also grow into the muscle of the uterus. […] There is no definite cause for adenomyosis but symptoms most often start late in the childbearing years after having children and usually settles after the menopause. 50% of women also have fibroids.

• #56 Adenomyosis You Might Have It and Not Know about It | Bangkok Hospital Headquarter

  https://www.bangkokhospital.com/en/bangkok/content/woman-beware-adenomyosis

  Because the symptoms are quite similar, adenomyosis is often misdiagnosed as uterine fibroids. However, the two conditions are not the same. […] The cause of adenomyosis remains unknown. Some studies suggest that women who have a family history of the condition or have had prior uterine surgery may be at risk for adenomyosis. […] Also, changes in estrogen hormone level may trigger the condition.

• #57 Adenomyosis – Causes, Symptoms and Treatment for Adenomyoma

  https://fibroidsecondopinion.com/adenomyosis/

  Adenomyosis is a benign condition where the uterine lining cells grow deep into the uterine muscle wall. […] For many years, adenomyosis has been suspected of causing infertility in women. […] The evidence that adenomyosis causes infertility includes: In women with adenomyosis, the muscles cells in the uterine wall swell and they function differently than normal uterine muscle cells. […] In women with adenomyosis, the lining cells of the uterus do not go through normal changes during the menstrual cycle. […] In women with adenomyosis, the uterine lining cells cause inflammation in the muscle wall which interferes with the movement of the fertilized egg inside the uterus. […] In women with adenomyosis, there are changes in the uterine lining cells that interfere with implantation of the fertilized embryo.

• #58 Adenomyosis – Causes, Symptoms and Treatment for Adenomyoma

  https://fibroidsecondopinion.com/adenomyosis/

  Adenomyosis is a benign condition where the uterine lining cells grow deep into the uterine muscle wall. […] For many years, adenomyosis has been suspected of causing infertility in women. […] The evidence that adenomyosis causes infertility includes: In women with adenomyosis, the muscles cells in the uterine wall swell and they function differently than normal uterine muscle cells. […] In women with adenomyosis, the lining cells of the uterus do not go through normal changes during the menstrual cycle. […] In women with adenomyosis, the uterine lining cells cause inflammation in the muscle wall which interferes with the movement of the fertilized egg inside the uterus. […] In women with adenomyosis, there are changes in the uterine lining cells that interfere with implantation of the fertilized embryo.

• #59 Adenomyosis – Everything You Need to Know

  https://oasisindia.in/blog/adenomyosis-everything-you-need-to-know/

  Adenomyosis affects a womans ability to conceive. But even though if a woman conceives, the pregnancy has associated risks such as miscarriage, low birth weight, pre-term labour, premature rupture of the amniotic membranes, uterine infections, etc. […] Issues in conception: The deformed structure of the uterus caused due to the thickening of the junctional zone, might block the movement of the sperm and immature eggs inhibiting conception. […] The function and receptivity of the endometrium are impaired due to inflammation and increased production of estrogen hormone. […] High chances of failed implantation are present as the endometrial tissue that invades into the myometrium continues to shed and bleed as it was designed to function. […] Mild and moderate adenomyosis pose a lower risk in pregnancy, however, the region of the infiltration of the uterine wall determines the severity of the impact of the condition. Whereas severe and advanced adenomyosis may put the mother and the baby at risk during pregnancy. The risks include preterm labour and miscarriage.

• #60 Adenomyosis – Causes, Symptoms and Treatment for Adenomyoma

  https://fibroidsecondopinion.com/adenomyosis/

  Adenomyosis is a benign condition where the uterine lining cells grow deep into the uterine muscle wall. […] For many years, adenomyosis has been suspected of causing infertility in women. […] The evidence that adenomyosis causes infertility includes: In women with adenomyosis, the muscles cells in the uterine wall swell and they function differently than normal uterine muscle cells. […] In women with adenomyosis, the lining cells of the uterus do not go through normal changes during the menstrual cycle. […] In women with adenomyosis, the uterine lining cells cause inflammation in the muscle wall which interferes with the movement of the fertilized egg inside the uterus. […] In women with adenomyosis, there are changes in the uterine lining cells that interfere with implantation of the fertilized embryo.

• #61 Adenomyosis: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2022/0100/p33.html

  Adenomyosis is a clinical condition where endometrial glands are found in the myometrium of the uterus. […] Risk factors for developing adenomyosis include increasing age, parity, and history of uterine procedures. […] Two theories prevail regarding the pathogenesis of adenomyosis. The first theory suggests that with injury of the endometrium, the basalis endometrium invaginates into the myometrium through an altered or interrupted junctional zone creating adenomyotic lesions. The tissue injury and repair theory may help explain why having a previous uterine procedure (e.g., cesarean delivery, dilation and curettage) increases the risk of subsequent adenomyosis. The second theory suggests that adenomyotic lesions arise from metaplasia of embryonic pluripotent Mllerian remnants. […] Common signs of adenomyosis include uterine enlargement, uterine tenderness with boggy consistency, and infertility. […] Impaired fertility in adenomyosis is thought to be attributable to abnormal thickening of the junctional zone of the myometrium, abnormal uterine peristalsis, and altered sperm transport.

• #62 Symptoms, Causes and Treatment for Adenomyosis

  https://www.cloudninefertility.com/blog/symptoms-causes-and-treatment-for-adenomyosis

  Adenomyosis is a disease in which the cells that line the inside of the uterus abnormally locate themselves in the uterine muculature. […] The actual cause of Adenomyosis is uncertain, a lot more studies in the field is needed. […] However, there are some theories which conclude the cause behind Adenomyosis, these are: Abnormal Uterine Development, Invasive Growth of Foreign Tissues, Uterine Inflammation and Childbirth. […] Adenomyosis alters the endometrial receptivity and gene expression and thus reduces the implantation chances i.e. pregnancy chances in a natural or ART cycle. […] The old blood collected in the musculature of the uterus acts as toxin and prevents pregnancy. […] There is progesterone hormone resistance in this condition, so miscarriages are common.

• #63 Symptoms, Causes and Treatment for Adenomyosis

  https://www.cloudninefertility.com/blog/symptoms-causes-and-treatment-for-adenomyosis

  Adenomyosis is a disease in which the cells that line the inside of the uterus abnormally locate themselves in the uterine muculature. […] The actual cause of Adenomyosis is uncertain, a lot more studies in the field is needed. […] However, there are some theories which conclude the cause behind Adenomyosis, these are: Abnormal Uterine Development, Invasive Growth of Foreign Tissues, Uterine Inflammation and Childbirth. […] Adenomyosis alters the endometrial receptivity and gene expression and thus reduces the implantation chances i.e. pregnancy chances in a natural or ART cycle. […] The old blood collected in the musculature of the uterus acts as toxin and prevents pregnancy. […] There is progesterone hormone resistance in this condition, so miscarriages are common.

• #64 Adenomyosis: Causes, Symptoms, & Treatment | AFC

  https://fibroidexpert.com/adenomyosis/

  Unfortunately, the cause of adenomyosis isn’t known. However, the condition is most often diagnosed in women later in their childbearing years and tends to resolve shortly after menopause. Some studies suggest that certain hormones, such as estrogen and progesterone, may be a factor. Other theories about the causes of adenomyosis include: […] Adenomyosis is a progressive reproductive tract condition that usually affects women who have given birth at least once. However, it can make conceiving the first time or subsequent times very difficult. […] At this time, researchers do not yet know whether adenomyosis alone can lead to infertility. However, it is common for patients with the condition to have decreased fertility rates, and in some cases, infertility. According to the Japan Society of OB/GYN, adenomyosis may be linked to a miscarriage rate of 50%, a preterm birth rate of 24.4%, and a fetal retardation rate of nearly 12%.

• #65 Adenomyosis – Wikipedia

  https://en.wikipedia.org/wiki/Adenomyosis

  A complex origin that includes multifactorial changes on both genetic and biochemical levels is likely. […] The tissue injury and repair (TIAR) theory is now widely accepted and suggests that uterine hyperperistalsis (i.e., increased peristalsis), during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface (EMI) region. […] That again leads to elevation of local estrogen in order to heal the damage. […] At the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. […] Iatrogenic injury of the junctional zone or physical damage due to placental implantation most likely results in the same pathological cascade.

• #66 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

• #67

  https://link.springer.com/article/10.1007/s13669-022-00326-7

  Several mechanisms are involved in the pathogenesis of adenomyosis: impaired gonadal sex steroids hormones receptors function, altered cell proliferation and differentiation, inflammatory reaction, processes of neuroangiogenesis and fibrosis. […] Adenomyosis is promoted by an imbalance between estrogens and progesterone signaling in women during reproductive life. […] The imbalance between estrogens and progesterone signaling is also caused by a decrease of progesterone activity, as suggested by the evidence that stromal cells of the functionalis and basalis endometrium of women with adenomyosis display a reduced immunoreactivity for isoform B of P receptor (PR-B), causing a loss of P effects. […] In addition, in ectopic endometrium, all three DNA Methyltransferases (DNMTs) are abnormally expressed, causing epigenetic changes.

• #68 Adenomyosis: Mechanisms and Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7932680/

  Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

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