Proangiogenic features in chronic pelvic pain caused by adenomyosis

Оразов, М Р; Носенко, Е. Н.; Radzinsky, V.E.; Хамошина, М.Б.; Lebedeva, M. G.; Sounov, M. A.

doi:10.1080/09513590.2016.1232902

Cited by 18 publications

(15 citation statements)

References 26 publications

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“…A comparative analysis of the number of macrophages in the myometrium in patients of the main group and the control group showed increased recruitment of these cells in adenomiosis complicated by the development of syndrome of pelvic pain. Moreover, CD68-positive cells were associated not only with areas of ectopic endometrial growth, but also the perivascular region and is the carrier of the nerves and center of the remodeling processes in the uterine wall in this pathology, as we have shown in previous studies [11,12].…”

Section: Resultssupporting

confidence: 75%

Immune-inflammatory predictors of the pelvic pain syndrome associated with adenomyosis

Оразов

Radzinsky

Носенко

et al. 2017

Gynecological Endocrinology

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The aim of the study was the analysis of immune inflammatory processes in the development of the pelvic pain syndrome associated with adenomyosis. For morphological examination were used 54 fragments of the myometrium obtained from patients after hysterectomy with pelvic pain on a background of diffuse adenomyosis of II-III degree, and 20 patients with painless form of adenomyosis. The identification of the macrophages distribution was held by means of an immune-hysto-chemical analysis of MAT (monoclonal antibody) for CD68. (Clone PG-M1, 'Diagnostic BioSystems', USA). The results of the study showed a significantly higher expression of CD68 (49.3 ± 2.3 vs. 21.2 ± 1.7 units. p < .01) in patients with painful adenomyosis form in areas of the ectopic endometrium, in the perivascular regions of the myometrium, as compared to those areas in women with painless group. We assume that these factors increase neurogenic inflammation and sensitivity of nociceptors in myometrium, activation of peripheral nerve fibers and, can act as triggers of the pelvic pain syndrome associated with adenomyosis.

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Section: Resultssupporting

confidence: 75%

Immune-inflammatory predictors of the pelvic pain syndrome associated with adenomyosis

Оразов

Radzinsky

Носенко

et al. 2017

Gynecological Endocrinology

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“…Immunoreactivity of S100A13 (Hayrabedyan et al ., 2005), MMP-2 and ROBO1, a receptor for SLIT, was also observed on the surface and within vascular endothelial cells (Nie et al ., 2011; Tokyol et al ., 2009). Glandular epithelial cells (Wang et al ., 2016; Li et al ., 2006; Goteri et al ., 2009; Liu et al ., 2016; Lai et al ., 2016; Orazov et al ., 2016), stromal cells (Li et al ., 2006; Goteri et al ., 2009; Li et al ., 2013; Orazov et al ., 2016) and endothelial cells (Goteri et al ., 2009; Orazov et al ., 2016) in the endometrium were stained positive for VEGF in women with adenomyosis whereas the staining in the control endometrium was either very low or not reported (Wang et al ., 2016; Li et al ., 2006; Goteri et al ., 2009; Liu et al ., 2016; Li et al ., 2013). The expression of COX-2 was observed not only in the endothelial, glandular (Ota et al ., 2001; Tokyol et al ., 2009) and stromal (Li et al ., 2013) cells but also in plasma cells (Ota et al ., 2001).…”

Section: Resultsmentioning

confidence: 99%

Role of angiogenesis in adenomyosis-associated abnormal uterine bleeding and subfertility: a systematic review

Harmsen

Wong

Mijatovic

et al. 2019

Human Reproduction Update

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BackgroundAdenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal vascularization in the endometrium in patients with adenomyosis, suggesting a role of angiogenesis in the pathophysiology of AUB and subfertility in adenomyosis and providing a possible treatment target.Objective and rationaleWe hypothesized that the level of abnormal vascularization and expression of angiogenic markers is increased in the ectopic and eutopic endometrium of adenomyosis patients in comparison with the endometrium of control patients. This was investigated through a search of the literature.Search methodsA systematic search was performed in PubMed and Embase until February 2019. Combinations of terms for angiogenesis and adenomyosis were applied as well as AUB, subfertility or anti-angiogenic therapy. The main search was limited to clinical studies carried out on premenopausal women. Original research articles focusing on markers of angiogenesis in the endometrium of patients with adenomyosis were included. Studies in which no comparison was made to control patients or which were not published in a peer-reviewed journal were excluded. A second search was performed to explore the therapeutic potential of targeting angiogenesis in adenomyosis. This search also included preclinical studies.OutcomesA total of 20 articles out of 1669 hits met our selection criteria. The mean vascular density (MVD) was studied by quantification of CD31, CD34, von Willebrand Factor (vWF) or factor-VIII-antibody-stained microvessels in seven studies. All these studies reported a significantly increased MVD in ectopic endometrium, and out of the six articles that took it into account, four studies reported a significantly increased MVD in eutopic endometrium compared with control endometrium. Five articles showed a significantly higher vascular endothelial growth factor expression in ectopic endometrium and three articles in eutopic endometrium compared with control endometrium. The vascular and pro-angiogenic markers α-smooth muscle actin, endoglin, S100A13, vimentin, matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, tissue factor (TF), DJ-1, phosphorylated mammalian target of rapamycin, activin A, folli- and myostatin, CD41, SLIT, roundabout 1 (ROBO1), cyclooxygenase-2, lysophosphatidic acid (LPA) 1,4-5, phospho signal transducer and activator of transcription 3 (pSTAT3), interleukin (IL)-6, IL-22 and transforming growth factor-β1 were increased in ectopic endometrium, and the markers S100A13, MMP-2 and -9, TF, follistatin, myostatin, ROBO1, LPA1 and 4-5, pSTAT3, IL-6 and IL-22 were increased in eutopic endometrium, compared with control endometrium. The anti-angiogenic markers E-cadherin, eukaryotic translation initiation factor 3 subunit and gene associated with retinoic-interferon-induced mortality 19 were decreased in ectopic endometrium and IL-10 in eutopic endometrium, compared with control endometrium. The staining level of vWF and two pro-angiogenic markers (NF-κB nuclear p65 and TF) correlated with AUB in patients with adenomyosis. We found no studies that investigated the possible relationship between markers of angiogenesis and subfertility in adenomyosis patients. Nine articles reported on direct or indirect targeting of angiogenesis in adenomyosis—either by testing hormonal therapy or herbal compounds in clinical studies or by testing angiogenesis inhibitors in preclinical studies. However, there are no clinical studies on the effectiveness of such therapy for adenomyosis-related AUB or subfertility.Wider implicationsThe results are in agreement with our hypothesis that increased angiogenesis is present in the endometrium of patients with adenomyosis compared with the endometrium of control patients. It is likely that increased angiogenesis leads to fragile and more permeable vessels resulting in adenomyosis-related AUB and possibly subfertility. While this association has not sufficiently been studied yet, our results encourage future studies to investigate the exact role of angiogenesis in the etiology of adenomyosis and related AUB or subfertility in women with adenomyosis in order to design curative or preventive therapeutic strategies.

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“…Furthermore, in our models, pre-operative dysmenorrhea is associated with higher risk of failure and surgical re-intervention. Adenomyosis has been suggested to be a factor influencing the increased occurrence of (post-ablation) pelvic pain [35][36][37][38]. Pain is a subjective outcome measure.…”

Section: Explaining the Modelsmentioning

confidence: 99%

Prediction of unsuccessful endometrial ablation: a retrospective study

et al. 2019

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Background: Endometrial ablation (EA) is a frequently used treatment for abnormal uterine bleeding, mainly due to the low risks, low costs and short recovery time associated with the procedure. On the short term, it seems successful, long-term follow-up however, shows decreasing patient satisfaction as well as treament efficacy. There even is a postablation hysterectomy rate up to 21%. Multiple factors seem to`influence the outcome of EA. Due to dissimilarities in and variety of these factors, it has not been possible so far to predict the success rate of EA based on pre-operative factors. Therefore, the aim of this study is to develop two prediction models to help counsel patients for failure of EA or necessity of surgical re-intervention within 2 years after EA. Methods: We designed a retrospective two-centred cohort study in Catharina Hospital, Eindhoven and Elkerliek Hospital, Helmond, both non-university teaching hospitals in the Netherlands. The study population consisted of 446 pre-menopausal women who underwent EA for abnormal uterine bleeding, with a minimum follow-up time of 2 years. Multivariate logistic regression analysis was used to create the prediction models. Results: The mean age of the patients was 43.8 years (range 20-55), 97.3% had complaints of menorrhagia, 57.4% of dysmenorrhoea and 61.0% had complaints of intermittent or irregular bleeding. 18.8% of patients still needed a hysterectomy after EA. The risk of re-intervention was significantly greater in women with menstrual duration > 7 days or a previous caesarean section, while pre-operative menorrhagia was significantly associated with success of EA. Younger age, parity ≥ 5 and dysmenorrhea were significant multivariate predictors in both models. These predictors were used to develop prediction models, which had a C-index of 0.71 and 0.68 respectively. Conclusion: We propose two multivariate models to predict the chance of failure and surgical re-intervention within 2 years after EA. Due to the permanent character of EA, the increasing number of post-operative failure and re-interventions, these prediction models could be useful for both the doctor and patient and may contribute to the shared decision-making.

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Proangiogenic features in chronic pelvic pain caused by adenomyosis

Cited by 18 publications

References 26 publications

Immune-inflammatory predictors of the pelvic pain syndrome associated with adenomyosis

Immune-inflammatory predictors of the pelvic pain syndrome associated with adenomyosis

Role of angiogenesis in adenomyosis-associated abnormal uterine bleeding and subfertility: a systematic review

Prediction of unsuccessful endometrial ablation: a retrospective study

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