Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology

Guo, Sun‐Wei

doi:10.1530/rep-22-0224

Cited by 25 publications

(12 citation statements)

References 227 publications

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“…Platelet-mediated EMT and FMT often cause fibrosis formation [ 37 ]. Guo’s group studies proved that platelet aggregation and activation are crucial in adenomyosis development [ 11 , 48 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Kobayashi

2023

IJERPH

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Adenomyosis is an estrogen-dependent gynecologic disease characterized by the myometrial invasion of the endometrial tissue. This review summarized the current understanding and recent findings on the pathophysiology of adenomyosis, focusing on repeated menstruation, persistent inflammation, and impaired spontaneous decidualization. A literature search was performed in the PubMed and Google Scholar databases from inception to 30 April 2022. Thirty-one full-text articles met the eligibility criteria. Repeated episodes of physiological events (i.e., endometrial shedding, damage, proliferation, differentiation, repair, and regeneration) during the menstrual cycle are associated with inflammation, angiogenesis, and immune processes. The decidualization process in humans is driven by the rise in progesterone levels, independently of pregnancy (i.e., spontaneous decidualization). Adenomyotic cells produce angiogenic and fibrogenic factors with the downregulation of decidualization-associated molecules. This decidualization dysfunction and persistent inflammation are closely related to the pathogenesis of adenomyosis. Recently, it has been found that the reproductive tract microbiota composition and function in women with adenomyosis differ from those without. An increase in opportunistic pathogens and a decrease in beneficial commensals may promote impaired defense mechanisms against inflammation and predispose women to uncontrolled endometrial inflammation. However, currently, there is no direct evidence that adenomyosis is linked to pre-existing inflammation and impaired spontaneous decidualization. Overall, persistent inflammation, impaired spontaneous decidualization, and microbiota dysbiosis (i.e., an imbalance in the composition and function of endometrial microbiota) may be involved in the pathophysiology of adenomyosis.

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Section: Resultsmentioning

confidence: 99%

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Kobayashi

2023

IJERPH

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“…These findings emphasize the potential therapeutic benefits of local anti‐TGF‐β1 injection for treating AM and provide new avenues for preventing AM‐related fibrosis 55 . SMM is another pathway of AM‐related fibrosis, which typically refers to the direct metaplasia of ectopic ESCs into smooth muscle cells under certain stimulating factors 49 . Zhang et al.…”

Section: The Role and Regulatory Mechanism Of Aamsmentioning

confidence: 89%

“…However, the precise induction mechanisms remain unclear. As fibrosis progresses, myofibroblasts secrete excessive amounts of ECM that is deposited around ectopic lesions, exacerbating AUB and pain 48,49 . Unfortunately, while existing treatments can only partly alleviate clinical symptoms, they cannot completely block and/or reverse fibrosis.…”

Section: The Role and Regulatory Mechanism Of Aamsmentioning

confidence: 99%

Macrophage polarization in adenomyosis: A review

Qiu,

Cao,

et al. 2024

American J Rep Immunol

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Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis‐associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.

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“…Medical treatment for adenomyosis, including gonadotropin-releasing hormone agonist (GnRH-a), oral contraceptives, and progestins, are limited in terms of effectiveness, tolerability, and costs . The current medical treatment strategy for adenomyosis is an unmet medical need . Furthermore, in the US population, 82.0% patients with adenomyosis choose hysterectomy to resolve their adenomyosis-associated symptoms and thereby lose their fertility .…”

Section: Introductionmentioning

confidence: 99%

“… 10 , 11 , 12 The current medical treatment strategy for adenomyosis is an unmet medical need. 13 , 14 Furthermore, in the US population, 82.0% patients with adenomyosis choose hysterectomy to resolve their adenomyosis-associated symptoms and thereby lose their fertility. 15 Therefore, there is a need to develop new therapeutic strategies and perform clinical studies focusing on the medical treatment of adenomyosis.…”

Section: Introductionmentioning

confidence: 99%

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms

et al. 2023

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ImportanceAdenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment.ObjectiveTo determine whether mifepristone is effective and safe for adenomyosis treatment.Design, Setting, and ParticipantsThis multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020.InterventionsParticipants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks.Main Outcomes and MeasuresThe primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations.ResultsIn total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was −6.63 (1.92) in the mifepristone group and −0.95 (1.75) in the placebo group (P &lt; .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P &lt; .001), CA125 (mean [SD] change from baseline: −62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P &lt; .001), platelet count (mean [SD] change from baseline: −28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P &lt; .001), and uterine volume (mean [SD] change from baseline: −29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P &lt; .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported.Conclusions and RelevanceThis randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability.Trial RegistrationClinicalTrials.gov Identifier: NCT03520439

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Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology

Cited by 25 publications

References 227 publications

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Macrophage polarization in adenomyosis: A review

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms

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