Explore the vast range of titles available.

Purpose To investigate and compare the clinical characteristics and risk factors between intrinsic and extrinsic adenomyosis (AM), as well as the differences in their perioperative management and findings in the two subtypes. Methods This observational study included women who were diagnosed with either intrinsic or extrinsic AM based on magnetic resonance imaging (MRI) and who underwent a hysterectomy with a subsequent pathological examination. Demographic characteristics, clinical features, treatment outcomes and associated factors were evaluated. Results 77 patients were classified in the intrinsic group and 54 in the extrinsic group. The results show that gravidity (P < 0.001), parity (P < 0.001), abortion (P < 0.001) and endometrial curettage (P = 0.017) were significantly higher in the intrinsic group, while the education level was lower in the intrinsic group (P = 0.012). Women in the extrinsic group had an earlier age of menarche (P = 0.026) and more commonly associated ovarian endometrioma (OMA) (P < 0.001) and deep infiltrating endometriosis (DIE) (P < 0.001). Dysmenorrhea was more severe in the extrinsic group (P = 0.009), whereas women in the intrinsic group had heavier menstrual blood loss (P < 0.001). Surgery time (P < 0.001), operative blood loss (P < 0.001), hospitalization cost (P < 0.001), and the intensity of postoperative medical treatment (P < 0.001) were significantly higher in the extrinsic group. Multivariate analysis showed that lower education level, higher gravidity and more endometrial curettage were significantly associated with intrinsic AM. OMA and DIE were more commonly associated to extrinsic AM. Conclusion These results suggest that intrinsic and extrinsic AM exhibit specific clinical profiles, perioperative characteristics and associated risk factors.

This study aimed to elucidate the role of microRNA-92a-3p (miR-92a-3p) in the pathogenesis of adenomyosis. We examined how miR-92a-3p, found in exosomes derived from ectopic lesions, influences the behaviour of endometrial cells, dorsal root ganglion (DRG), and human umbilical vein endothelial cells (HUVECs) and explored its potential as a non-invasive biomarker. Our findings revealed that miR-92a-3p was significantly upregulated in exosomes derived from ectopic adenomyotic lesions. This upregulation correlated with enhanced migration and invasion of eutopic endometrial cells, DRG, and HUVECs. Furthermore, this study demonstrated a significant correlation between miR-92a-3p levels in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidated an exosomal signalling process involving miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Our findings highlight upregulated miR-92a-3p in biofluid exosomes as a promising non-invasive biomarker for diagnosing and monitoring adenomyosis and unveil novel targets and strategies for improved clinical management.

Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding \"invagination\" and \"metaplasia\" theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial ( LGR5 +) and invasive stromal ( PKIB +) subpopulations, along with WFDC1 + progenitor cells, supporting a complex interplay between \"invagination\" and \"metaplasia\" theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving pleiotrophin, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers’ presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

Adenomyosis (AM) is a common and challenging disease in gynecological clinics, which adversely affects women’s physical and mental health. Despite the growing number of studies, the mechanisms associated with the growth of the lesion are poorly understood. Studies show that abnormal proliferation, apoptosis, and migration in ectopic endometrial stromal cells (EESc) of AM may contribute to the development and progression of AM. Understanding the underlying molecular mechanisms can significantly contribute to diagnosing and treating AM. In the present study, EESc was isolated and cultured from the ectopic endometrium of patients with AM. These cells were treated with a PI3K/AKT activator (740 Y-P) and an inhibitor (LY294002), while the expression of microRNA-21 (miR-21) was interfered with. The effects of miR-21 on the apoptosis and autophagy of EESc, as well as the associated mechanisms, were investigated from multiple perspectives. Here, we found that 740 Y-P could significantly promote proliferation, inhibit apoptosis of EESc, and increase the expression of mTOR and p-mTOR proteins in EESc. Moreover, activating miR-21 enhanced the pro-migration effect of 740 Y-P and reversed the pro-apoptotic effect of LY294002, reducing the apoptosis rate and increasing the migration ability of EESc. Our investigation revealed that miR-21 can inhibit apoptosis and autophagy and promote migration of EESc. This effect is likely mediated via the PI3K/AKT/mTOR pathway.

Spontaneous uterine rupture outside of pregnancy is exceptionally rare, with adenomyosis potentially acting as a structurally weakening substrate. Most reports involve gravid patients, underscoring the unusual nature of nongravid presentations. We report the case of a 26-year-old nongravid, nulliparous woman who presented with sudden, diffuse abdominal pain and hemorrhagic shock. Imaging revealed a markedly enlarged, heterogeneous uterus with hemoperitoneum. Emergency laparotomy evacuated approximately 3000 mL of blood. Multiple transmural ruptures precluded repair, necessitating total hysterectomy with adnexal preservation. Histopathology confirmed diffuse adenomyosis with extensive hemorrhagic necrosis. This case highlights that in reproductive-age women presenting with an acute abdomen, a negative pregnancy test, and an enlarged heterogeneous uterus, spontaneous rupture secondary to adenomyosis should be considered. Early resuscitation and definitive surgical management are critical, and proactive counseling is recommended for patients with severe adenomyosis who may be at risk for catastrophic decompensation.

ObjectiveRecent studies report a link between endometriosis and ovarian cancer (OC). Using a population-based cohort study to confirm the association between endometriosis and cancer is desirable. We thus examined the magnitude of the risks of OC, endometrial cancer (EC), breast cancer, colorectal cancer (CRC), and other cancers in women with newly diagnosed endometriosis or adenomyosis (internal endometriosis).Methods/MaterialsWomen older than 20 years with claims data between 2003 and 2005 were identified from the Longitudinal Health Insurance Dataset containing 1 million individuals randomly sampled from the National Health Insurance Research Database. Those with preexisting malignancies, hysterectomy, or oophorectomy were excluded. The endometriosis cohort (n = 2266, including 768 cases of pure adenomyosis) and comparison cohort (n = 9064), formed by 1:4 matching, were followed up until incidence cancer, dropout, or December 31, 2008. Outcome measures included cancer incidence and adjusted hazard ratio by Cox model adjusted for age group, comorbidities, and endometriosis medication use.ResultsWith 9842 person-years of follow-up in endometriosis cohort and 36,274 person-years of follow-up in comparison cohort, there were increased risks of all cancers (adjusted hazard ratio, 1.8; 95% confidence interval, 1.4–2.4), OC (4.56, 1.72–12.11), and EC (4.05, 1.20–13.66). The ovarian endometriosis group was associated with increased risk of subsequent OC (4.37, 1.07–17.83). The adenomyosis group was strongly associated with both OC (5.50, 1.95–15.50) and EC (5.13, 1.36–19.40). Increased risk of subsequent CRC was observed in women with adenomyosis with coexistent endometriosis at other sites (13.04, 2.21–77.04). However, no statistically significant increased risk of breast or other cancers was observed.ConclusionsHaving limitations such as lacking of parity information which may affect the magnitude of risk estimates, this study demonstrates that ovarian endometriosis has a 4-fold increased risk of OC. Adenomyosis may associate with a 4- to 5-fold increased risk of OC and EC, and unexpectedly, a 13-fold increased risk of CRC.

Background Adenomyosis and endometriosis are hormone-dependent benign gynecological disorders with overlapping features suggesting that they may share a common origin despite being considered distinct entities. This study compares the expression of candidate genes in the eutopic endometrium of diffuse adenomyosis, ovarian endometriosis, co-existent adenomyosis–endometriosis, and controls. Methods Publicly available transcriptomic datasets comprising endometrial tissue of women with adenomyosis, endometriosis, and women with healthy endometrium were analyzed, and overlapping differentially expressed genes (DEGs) were determined. Gene ontology and pathway enrichment analyses were performed to determine shared biological processes. A protein–protein interaction (PPI) network was constructed using the overlapping DEGs and the key genes identified. These genes and corresponding proteins were further validated in the patient population (25 women in each group of diffuse adenomyosis, ovarian endometrioma, co-existent adenomyosis–endometriosis). Thirty women with healthy endometrium having infertile male partners were recruited as controls for comparison purposes. Receiver operating characteristic (ROC) curves were generated for the key genes to evaluate their discriminatory accuracy in classifying isolated adenomyosis. Finally, the gene expressions were correlated with patient clinical characteristics. Results 23 significant DEGs (log2 fold-change > 1, p  < 0.05) were found to be common between adenomyosis and endometriosis datasets, with serine-type endopeptidase activity emerging as the most enriched molecular function. PPI network analysis identified MMP7 , MMP11 , IGFBP5 , SERPINA1 , THBS1 as the hub genes. In addition, MMP9 and TIMP1 exhibited a strong association with the hub gene network. Experimental validation showed altered expression in adenomyosis as compared to controls and other disease groups. MMP9 and MMP7 showed strong discrimination for adenomyosis vs. endometriosis [area under the curve (AUC) = 0.93] and co-existent cases (AUC = 0.97), respectively. The expression of most of the genes in the co-existent group did not align with adenomyosis or endometriosis. MMP7 expression positively correlated with uterine volume in adenomyosis; MMP11 could be negatively associated with myometrial wall thickness ratio. Conclusions Distinct expression profiles were observed in diffuse adenomyosis versus ovarian endometriosis and co-existent phenotype. Expression of key genes indicated enhanced ECM remodeling in adenomyosis, with MMP7, MMP9, and MMP11 emerging as potential discriminatory markers. The divergent expressions in the co-existent phenotype suggest distinct molecular mechanisms that merit further study.

Reduced lymphoid enhancer-binding factor 1 (LEF1) expression in patients with adenomyosis during the mid-secretory phase leads to impaired endometrial receptivity, affecting embryo implantation. This study investigated the molecular mechanisms underlying reduced endometrial receptivity in 25 adenomyosis patients and 25 controls. Functional experiments were conducted using human endometrial stromal cells (HESCs) and TERT-immortalized HESCs(T-HESCs), with final validation performed using a mouse model. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyses revealed that patients with adenomyosis showed a marked decrease in LEF1 expression in the stromal cells of the endometrium during the mid-secretory phase. In vitro experiments demonstrated that LEF1 knockdown in stromal cells led to impaired decidualization. Transcriptome sequencing, dual-luciferase reporter assays, and chromatin immunoprecipitation (ChIP) experiments showed that LEF1 could bind to the promoter region of interleukin (IL)-11 and promote its transcription, and IL-11 expression was also found to be downregulated in adenomyosis patients. Overexpression of IL-11 rescued the impaired decidualization caused by decreased LEF1 expression. In the in vitro co-culture model, LEF1/IL-11 knockdown led to a reduction in embryo implantation area, which was partially restored upon IL-11 overexpression. In the adenomyosis mouse model, we observed a decrease in LEF1 expression and a reduction in implantation sites compared to control mice, accompanied by impaired decidualization and receptivity. Notably, supplementation with IL-11 restored the number of implantation sites. The decrease in fertility due to reduced endometrial receptivity in adenomyosis patients is a significant clinical issue in assisted reproductive technology. This research provides insights into one potential molecular mechanism underlying this decreased receptivity, with a specific focus on the reduced expression of LEF1 in the endometrial stromal cells during the mid-secretory phase in adenomyosis patients. Our findings offer new perspectives for clinical strategies to improve endometrial receptivity in patients with adenomyosis, potentially enhancing their chances of successful pregnancy.