Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Dec;161(4):407-412
Endometriosis with an aberrant immunophenotype: Challenging differential diagnosis of glandular lesions in the pelvic lymph nodes.
Vlckova D1, Lenz J2,3,4, Chvatal R1, Tihon J5, Kavka M5, Uncapher L6.
We describe an unusual case of pelvic lymph node endometriosis with an aberrant immunophenotype mimicking metastasis of adenocarcinoma. A 37-year-old patient with a history of invasive cervical adenocarcinoma stage pT1a2 is presented. Due to insufficient loop electrosurgical excision procedure (LEEP) conization, total laparoscopic hysterectomy with pelvic lymphadenectomy was indicated. Intraoperatively, the diagnosis of deep infiltrating endometriosis of parametrial ligament and vesicouterine pouch, endometrioma of the left ovary and Allen Master’s syndrome was suspected; the patient had no history or clinical symptoms of endometriosis. A PubMed search of similar cases was followed by a comparison to this case and discussion of the differential diagnosis of glandular lesions in the pelvic lymph nodes is reported.
Histological investigation showed no residual neoplasia; the diagnosis of endometriosis was confirmed. An interesting microscopic finding was represented by a solitary glandular lesion in one pelvic lymph node. Using immunohistochemistry, it was demonstrated that there was a complete loss of oestrogen and progesterone receptor expression (unlike parametrial ligament endometriosis). The diagnosis of endometriosis was based on the presence of endometrial stroma; malignancy was excluded by bland cytomorphologic features and results of immunohistochemical examination.
This type of aberrant of the endometriotic gland immunophenotype has never been presented in the scientific literature before. This finding plays a significant role from the pathology standpoint and, perhaps more importantly, from the clinical standpoint. An asymptomatic patient with a correct diagnosis of lymph node endometriosis did not undergo excessive treatment for false positive diagnosis of metastatic cervical adenocarcinoma.
Hum Pathol. 2017 Sep;67:211-216
Postablation neuroma of the myometrium-a report of 5 cases.
When hysterectomy is performed for chronic pelvic pain, routine pathology examination often provides no explanation. However, analysis of small uterine nerves using immunostains may help to address this deficiency. Small uterine nerves tend to be sparse or absent in wide areas of normal myometrium. Some studies of uterine nerves have suggested that endometriosis, adenomyosis, and fibroids are not inherently painful, with increased small nerves in the inner uterine wall associated with the history of pelvic pain. Although such areas may appear normal on hematoxylin and eosin (H&E), we have found a subtle inner wall lesion termed inner myometrial elastosis, best detected with trichrome or elastic stains, which may be a reaction to microscopic tears of inner myometrium. Such tears may induce increased inner wall innervation via the generation of nerve growth factor in granulation tissue. In the course of studying uterine nerves with immunostains, we found 5 cases with florid nerve proliferation, after deep endometrial ablation for abnormal uterine bleeding led to increased pelvic pain. We suggest that immunostains for postablation neuromas should be done in hysterectomies when pelvic pain increases after endometrial ablation. This may offer gynecologists and their patients an objective finding with a rational, scientific explanation for the pelvic pain.
Sex Reprod Healthc. 2017 Oct;13:35-40
Minimal clinically important difference for pain on the VAS scale and the relation to quality of life in women with endometriosis.
The minimal important difference can be helpful in interpreting data from clinical trials. The objective of the study was to calculate the minimal important difference for improvement on the VAS scale for women with endometriosis.
A prospective study was conducted to evaluate the effect of pertubation with lignocaine on dysmenorrhea and quality of life in women with endometriosis. Data collected in the trial were used for additional analyses in the present descriptive study. Eligible women (n=37) had endometriosis with pain>VAS 50mm (visual analogue scale).
MAIN OUTCOME MEASURES:
In a questionnaire, women evaluated their maximum pain on the VAS- scale during every menstrual period before and after treatment. They also estimated the changes in overall pain level by answering the response categories “much better”, “somewhat better”, “about the same”, “somewhat worse” or “much worse”. The women were grouped according to their own estimation of change in pain intensity after four months. The minimal important differences for change on the VAS scale correlate to the mean change for women who felt “somewhat better” (n=18) excluding those who were pain free (n=2).
The minimal important difference for improvement on the VAS scale was found to be -39mm and/or -49%.
If the patients have a pain level of at least 50mm on VAS scale at inclusion, the cut off for success in clinical trials is suggested to be defined as an either >40mm or a >50% decrease on VAS scale. Trial registry ClinicalTrials.gov Identifier: NCT01329796.
Reprod Sci. 2017 Jan 1:
p38 Mitogen-Activated Protein Kinase is Involved in the Pathogenesis of Endometriosis by Modulating Inflammation, but not Cell Survival.
Cakmak H1,2, Seval-Celik Y1,3, Arlier S4, Guzeloglu-Kayisli O4, Schatz F4, Arici A1, Kayisli UA4.
Local pro-inflammatory environment and enhanced cell survival contribute to the endometriosis development. A serine/threonine kinase p38 mitogen-activated protein kinase (MAPK) mediates intracellular signaling of cytokine production, cell proliferation, and apoptosis in different cell types. The current study compares p38 MAPK activity in normal endometrium and endometriosis, and assesses role(s) of p38 MAPK on cytokine production and cell survival in endometriosis.
Immunohistochemical levels of total and phosphorylated (active) p38 MAPK as well as its correlation with interleukin 8 (IL-8) expression, and cell proliferation and apoptosis were compared in normal human endometrium and endometriosis. The action of p38 MAPK on pro-inflammatory cytokine-induced IL-8 and monocyte chemotactic protein (MCP)-1 expression in endometriotic cells were assessed by enzyme-linked immunosorbent assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell survival, 5-bromo-2′-deoxyuridine incorporation, and Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assays were used to determine the function of p38 MAPK in cultured human endometriotic stromal cell proliferation and apoptosis.
p38 MAPK activity was significantly higher in both eutopic and ectopic endometria compared to normal endometria during late proliferative and early secretory phases ( P < .05). Increased p38 MAPK activity in endometriotic cells correlated with IL-8 expression (Pearson correlation coefficient r = 0.83, P < .01), but not with apoptosis in vivo. The pro-inflammatory cytokines IL-1β and tumor necrosis factor (TNF)-α induced activation of p38 MAPK. Inhibition of p38 MAPK activity blocked IL-1β and TNF-α-induced IL-8 and MCP-1 secretion in cultured endometriotic stromal cells ( P < .05), but did not impact on endometriotic cell survival.
These results suggest that rather than modulating cell survival, increased p38 MAPK activity in endometriotic cells contributes to the pathogenesis of endometriosis by promoting the local inflammatory milieu.
Eur J Obstet Gynecol Reprod Biol. 2017 Oct;217:34-37
Extra pelvic endometriosis: Retrospective analysis on 200 cases in two different countries.
Matalliotakis M1, Goulielmos GN2, Kalogiannidis I3, Koumantakis G4, Matalliotakis I5, Arici A6.
The purpose of the study was to review patients’ characteristics and the location of extrapelvic endometriosis.
Out of 1000 women with endometriosis during a 20year period, we found 200 cases with extra pelvic endometriosis. Medical reports were evaluated and the diagnosis was confirmed on the pathological specimen. This study involved cases from two different geographical areas, New Haven and Crete. The age, parity, symptoms, previous surgeries, diagnostic modalities, histopathological evaluation and location of endometriotic implants found in other areas were recorded and analyzed from the patient’s charts.
MAIN OUTCOME MEASURE(S):
Statistical methods included x2 and Mann-Whitney U test s measuring incidence of right-VS left sided endometriosis.
200 patients with extrapelvic endometriosis and 800 patients with pelvic endometriosis were included in the study. The gastrointestinal tract represents the most common location of extrapelvic endometriosis with 104/200(52%) cases (p<0, 01), followed by the urinary system with70/200(35%) cases. We observed the Left-sided ureter being involved in 49/200(24, 5%) cases, significantly higher compare with the right-sided ureter 21/100(10, 5%) (p <0, 01). All women had similar characteristics involving age, weight, main complaints, age of menarche, endometriosis stages, gravid and family history of endometriosis.
The gastrointestinal tract and the urinary system are the most common sites of the extrapelvic endometriosis, which was obvious in both countries. Moreover, we observed that there are no significant differences in demographic variants, menstrual and reproductive characteristics in women with extrapelvic and pelvic endometriosis.
Mol Med Rep. 2017 Oct;16(4):5611-5617.
Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor.
Cao H1, Wei YX1, Zhou Q2, Zhang Y2, Guo XP3, Zhang J1.
Endometriosis, which affects up to 10% of women of reproductive age, is defined as endometrial-like gland and stroma tissue growths outside the uterine cavity. Despite increasing research efforts, there are no current effective treatment methods for this disease, therefore investigations for therapeutic strategies are of primary concern. In preliminary work, the authors demonstrated that curcumin inhibits endometriosis in vivo. The present in vitro study aimed to investigate the association between endometriotic stromal cells and curcumin and to clarify the underlying mechanism of action. A total of 14 patients with endometriosis were enrolled in the present study. The purity of endometrial stromal cell cultures was proven by standard immunofluorescent staining of vimentin. The cell proliferation and curcumin effects on endometrial stromal cells were assessed by the MTT assay and Hematoxylin and Eosin staining. For cell cycle analysis, phase distribution was detected by flow cytometry. Vascular endothelial growth factor (VEGF) protein expression was examined using immunohistochemistry staining. Apoptosis was assessed using Annexin V‑fluorescein isothiocyanate staining. The results indicated that the treatment of curcumin decreased human ectopic and eutopic stromal cell growth. Following treatment with curcumin, human endometriotic stromal cells demonstrated an increased percentage of G1‑phase cells and decreased percentages of S‑phase cells, particularly in the group treated with 50 µmol/l curcumin. Treatment with curcumin additionally decreased expression of VEGF. The data provide evidence that curcumin reduces cell survival in human endometriotic stromal cells, and this may be mediated via downregulation of the VEGF signaling pathway.
Mol Med Rep. 2017 Nov;16(5):6077-6080.
Genetic association study in a three-generation family with seven members with endometriosis.
Matalliotakis M1, Zervou MI2, Matalliotaki C1, Arici A3, Spandidos DA4, Matalliotakis I1, Goulielmos GN2.
The aim of this study was to investigate whether five single nucleotide polymorphisms (SNPs), associated with endometriosis, may confer new insight towards a genotype‑phenotype association with endometriosis. We studied a three-generation family with seven women who had endometriosis. Blood specimens were obtained from all the affected female family members. The entire family was genotyped for five SNPs mapped to WNT4, VEZT, FSHB and IL-16 genetic loci. We further evaluated the members of the family with endometriosis and described all obstetric and gynecological complications caused by the disease in these seven women. The five SNPs analyzed did not reveal any genotype-phenotype correlation with the disease. The members of the family with endometriosis showed a variety of clinical manifestations and complications. None of the five genetic markers examined correlated genotype with phenotype in the case of the Greek three-generation family examined. Therefore, we conclude that more gene polymorphisms must be investigated in the members of this family to gain insight regarding a genotype‑phenotype correlation in endometriosis and the potential development of a personalized care for the patients based on these data.
Zhonghua Fu Chan Ke Za Zhi. 2017 Aug 25;52(8):526-532.
Clinical characteristics and risk factors of pelvic mass in women after hysterectomy for benign disease.
Xu XX1, Li T, Dai Y, Zhang JJ, Lang JH, Leng JH.
Objective: To explore how to reduce the incidence of pelvic mass after hysterectomy, and to evaluate clinical characteristics and the risks. Methods: A retrospective study was carried out in 85 patients who returned for surgery due to a pelvic mass after prior hysterectomy for benign disease at Peking Union Medical College Hospital from January 2011 to June 2016. Results: The majority of pelvic masses arising after hysterectomy and requiring surgery were benign (74%, 63/85), while 19% (16/85) were malignant and 7% (6/85) were borderline. The most common type was ovarian endometrioma (24%, 20/85) which usually occurs within the 5 years (16 cases), however, ovarian tumors (18 cases) were more likely to occur ≥10 years after hysterectomy. Characteristics associated with significantly increased likelihood of ovarian endometrioma were mainly ascribed to younger age [(47±5) years old], prior presence of endometriosis or adenomyosis (65%, 13/20) and shorter time to pelvic mass onset [(3±3) years], as opposed to ovarian tumors (all P<0.01). Additionally, higher number of prior abdominal surgeries significantly intensified the risk (RR=9.410, 95%CI: 1.099-80.564, P=0.041). Conclusions: The occurrence of pelvic mass after hysterectomy is tightly related to prior histologic findings, and particularly for ovarian endometrioma. Higher number of prior abdominal surgery will exacerbated the risk. It is effective to prevent the pelvic mass in women after hysterectomy if treat patients for the purpose of the risk factors.
BMJ. 2017 Aug 29;358:j3778.
History of breast feeding and risk of incident endometriosis: prospective cohort study.
Farland LV1,2, Eliassen AH3,4, Tamimi RM3,4, Spiegelman D3,4, Michels KB3,5, Missmer SA3,6,7.
Objective To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women.Design Prospective cohort study.Setting Nurses’ Health Study II, 1989-2011.Participants 72 394women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea. Main outcome measures Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis.Results Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100 000 person years compared with 184 cases/100 000 person years in women who reported a lifetime total of ≥36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P<0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P<0.001 for trend). Women who breastfed for ≥36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced by postpartum amenorrhea (% mediated was 34% (95% confidence interval 15% to 59%) for total breast feeding and 57% (27% to 82%) for exclusive breast feeding).Conclusion Among women who experienced at least one pregnancy that lasted at least six months, breast feeding was inversely associated with risk of incident endometriosis. This association was partially, but not fully, influenced by postpartum amenorrhea, suggesting that breast feeding could influence the risk of endometriosis both through amenorrhea and other mechanisms. Given the chronic and incurable nature of endometriosis, breast feeding should be further investigated as an important modifiable behavior to mitigate risk for pregnant women.
Hum Reprod. 2017 Aug 1;32(8):1549-1555.
Transparent collaboration between industry and academia can serve unmet patient need and contribute to reproductive public health.
The pharmaceutical and device industry has greatly contributed to diagnostic and therapeutic approaches in reproductive medicine in a very highly regulated environment, ensuring that development and manufacturing follow the highest standards. In spite of these achievements, collaboration between industry and physicians/academia is often presented in a negative context. However, today more than ever, partnership between industry and academia is needed to shorten the timeline between innovation and application, and to achieve faster access to better diagnostics, drugs and devices for the benefit of patients and society, based on complementary knowledge, skills and expertise. Such partnerships can include joined preclinical/clinical and post-marketing research and development, joint intellectual property, and joint revenue. In Europe, the transparency of this collaboration between pharmaceutical industry and medical doctors has been made possible by the Compliance and Disclosure Policy published by the European Federation of Pharmaceutical Industries and Associations (EFPIA), which represents the major pharmaceutical companies operating in Europe, and includes as members some but not all companies active in infertility and women’s health. Under the EFPIA Disclosure Code of conduct, companies need to disclose transfers of value including amounts, activity type and the names of the recipient Health Care Professionals and Organizations. EFPIA member companies have also implemented very strict internal quality control processes and procedures in the design, statistical analysis, reporting, publication and communication of clinical research, according to Good Clinical Practice and other regulations, and are regularly inspected by competent authorities such as the US Food and Drug Administration (FDA) or European Medicines Agency (EMA) for all trials used in marketing authorization applications. The risk of scientific bias exists not only in the pharmaceutical industry but also in the academic world. When academics believe in a hypothesis, they may build their case by emphasizing the arguments supporting their case, and either refute, refuse, oppose or ignore arguments that challenge their assumptions. A possible solution to reduce this bias is international consensus on study design, data collection, statistical analysis and reporting of outcomes, especially in the area of personalized reproductive medicine, e.g. to demonstrate superiority or non-inferiority of personalized ovarian stimulation using biomarkers. Equally important is that declarations of interest are reported transparently and completely in scientific abstracts and publications, and that ghost authorship is replaced by proactive and clear co-authorship for experts from industry where such co-authorship is required based on the prevailing ICMJE criteria. In that context, however, reviewers should stop believing that publications by industry authors only, or by mixed groups of co-authors from industry and academia, are more prone to bias than papers from academic groups only. Instead, the scientific quality of the work should be the only relevant criterion for acceptance of papers or abstracts, regardless of the environment where the work was done. In the end, neutrality does not exist and different beliefs and biases exist within and between healthcare professionals and organizations and pharmaceutical industries. The challenge is to be transparent about this reality at all times, and to behave in an informed, balanced and ethical way as medical and scientific experts, taking into account compliance and legal regulations of both industry and academic employers, in the best interest of patients and society.
Hum Reprod. 2017 Sep 1;32(9):1812-1818.
Bowel Endometriosis Syndrome: a new scoring system for pelvic organ dysfunction and quality of life.
Riiskjær M1, Egekvist AG1, Hartwell D2, Forman A1, Seyer-Hansen M1, Kesmodel US3.
Is it possible to develop a validated score that can identify women with Bowel Endometriosis Syndrome (BENS) and be used to monitor the effect of medical and surgical treatment?
The BENS score can be used to identify women with BENS and to monitor the effect of medical and surgical treatment of women suffering from bowel endometriosis.
WHAT IS KNOWN ALREADY:
Endometriosis is a heterogeneous disease with extensive variation in anatomical and clinical presentation, and symptoms do not always correspond to the disease burden. Current endometriosis scoring systems are mainly based on anatomical and surgical findings.
STUDY DESIGN, SIZE, DURATION:
The score was developed and validated from a cohort of 525 women with medically or surgically treated bowel endometriosis from Aarhus and Copenhagen University Hospitals, Denmark.
PARTICIPANTS/MATERIALS, SETTING AND METHODS:
Patients filled in questionnaires on pelvic pain, quality of life (QoL) and urinary, sexual and bowel function. Items were selected for the final score using clinical and statistical criteria. The chosen variables were included in a multivariate analysis. Individual score values were designated items to form the BENS score, which was divided into ‘no BENS’, ‘minor BENS’ and ‘major BENS.’ Internal and external validations were performed.
MAIN RESULTS AND THE ROLE OF CHANCE:
The six most important items were ‘pelvic pain’, ‘use of analgesics’, ‘dyschezia’, ‘straining to urinate’, ‘fecal urgency’ and ‘satisfaction with sexual life’. The range of the BENS score (0-28) was divided into 0-8 (no BENS), 9-16 (minor BENS) and 17-28 (major BENS). External validation showed a significant association between BENS score and QoL (P = 0.0001).
LIMITATIONS, REASONS FOR CAUTION:
The BENS scoring system is limited by the fact that it was developed from a single endometriosis unit in Denmark, making it susceptible to social, cultural and demographic bias.
WIDER IMPLICATIONS OF THE FINDINGS:
It is the first endometriosis classification system to be based directly on the symptomatology of the patient. Validation in other languages will promote comparison of treatments and results across borders.
STUDY FUNDING/COMPETING INTEREST(S):
No external funding was either sought or obtained for this study. A.F. is an investigator for Bayer, outside this work.
Hum Reprod. 2017 Sep 1;32(9):1855-1861.
Mental health in women with endometriosis: searching for predictors of psychological distress.
Facchin F1, Barbara G2, Dridi D2, Alberico D2, Buggio L2, Somigliana E2, Saita E1, Vercellini P2.
What factors affect the mental health of women with endometriosis?
Not only pelvic pain, but also individual characteristics (i.e. self-esteem, body esteem and emotional self-efficacy), time from diagnosis and intimate relationship status influence the psychological health of endometriosis patients.
WHAT IS KNOWN ALREADY:
The negative impact of endometriosis on mental health has been widely demonstrated by the research literature, along with the fact that presence and severity of pelvic pain are associated with anxiety and depression. However, endometriosis is a complex multidimensional disease and factors other than pelvic pain, including individual differences, may contribute to explain the variability in women’s mental health.
STUDY DESIGN, SIZE, DURATION:
This cross-sectional study was conducted between 2015 and 2017 at an Italian academic department of obstetrics and gynaecology.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
A total of 210 consecutive endometriosis patients (age: 36.7 ± 7.0 years) were included. Demographic and endometriosis-related information was collected. Individual differences were assessed using validated measures evaluating self-esteem, body esteem and emotional self-efficacy. The Hospital Anxiety and Depression Scale (HADS) and the Ruminative Response Scale (RRS) were used to evaluate mental health.
MAIN RESULTS AND THE ROLE OF CHANCE:
Based on the extant literature, we identified three categories of putative predictors (demographic variables, endometriosis-related factors and individual differences i.e. ‘self’), whose psychological impact was examined using a hierarchical multiple regression approach. Being in a stable relationship (coded 1 [‘yes’] or 0 [‘no’]) was associated with decreased rumination (RRS: β = -0.187; P = 0.002). A shorter time from diagnosis was associated with greater anxiety (HADS-A: β = -0.177; P = 0.015). Pelvic pain severity and ‘self’ were associated with all mental health variables (Ps < 0.01). Greater self-esteem, body esteem, and emotional self-efficacy were correlated with better psychological outcomes (Ps < 0.01).
LIMITATIONS REASONS FOR CAUTION:
Sexual functioning, pregnancy, infertility, cultural differences and gender beliefs have been found to be important in women with endometriosis. In our regression model, we did not test the psychological impact of these variables and this should be acknowledged as an important limitation. Moreover, the cross-sectional (rather than longitudinal) nature of this study does not allow a full examination of the temporal relationship between endometriosis and psychological outcomes.
WIDER IMPLICATIONS OF THE FINDINGS:
Factors other than pelvic pain can significantly affect the mental health of women with endometriosis, and the role of individual differences requires further investigation. Targeted multidisciplinary interventions should include evaluation and enhancement of self-esteem and self-efficacy to improve women’s psychological health.
Reprod Sci. 2017 Jan 1:1933719117728804.
Histopathological Alterations in Fetal Membranes of Women With Endometriosis.
Marcellin L1,2, Méhats C1, Gogusev J1.
Previously, we reported endometriotic-like decidual lesions in contact with the fetal membranes (FMs) in 11 pregnant women with severe endometriosis. In this report, an extensive histomorphological analysis was performed on the FMs of 19 pregnant women with deep infiltrating endometriosis (DIE) at term pregnancy and who delivered by cesarean delivery before labor. On gross examination, all samples showed increased thickness, de novo microvessel formation, and small-size excrescences distributed along the membrane circumference. Histological examination of FM fragments sampled from the placenta edges or from the cesarean incision line showed fibrinoid necrosis and connective tissue accumulation in the amnion, chorion, and decidual layers in most of the 19 women with DIE. Papillary tufting and epithelial cell multilayering at the surface of the amnion layer were found in 3 of the 19 women with DIE. In 14 of the 19 women with DIE, the trophoblastic layer was disrupted by dense extracellular material, degenerative villi, and inflammatory infiltrates. Cystic gland-like structures were found in the decidual layer in all the 19 women with DIE, which were surrounded by irradiating small vessels and scattered inflammatory cells. The relationship between these peculiar histological changes and the endometriotic status of the pregnant women is still unclear. Sustained examination of FMs in women with DIE is needed to fully evaluate the defaults in these tissue structures and to establish whether these defaults have clinical impact on the pregnancy course.
Am J Reprod Immunol. 2017 Nov;78(5).
CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs.
Diao R1, Wei W2, Zhao J2,3, Tian F1, Cai X1, Duan YG4.
The level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown.
ELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Expressions of Bcl2, MMP2, MMP9, and p-AKT/AKT were analyzed by Western blot.
Peritoneal fluid concentration of CCL19 in patients with endometriosis was higher than that in controls. Those patients with moderate/severe endometriosis had significantly higher peritoneal fluid concentrations of CCL19 compared to those with minimal/mild endometriosis. Higher CCL19 and CCR7 were found in the endometrium with endometriosis compared to control. CCL19 significantly enhanced ESC proliferation and invasion through CCR7 via activating PI3K/Akt signal pathways. CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, Bcl2, MMP2, and MMP9 in ESCs.
These data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway.
BJOG. 2017 Aug;124 Suppl 3:59-63.
Ultrasound-guided high-intensity focused ultrasound treatment for abdominal wall endometriosis: a retrospective study.
Luo S1, Zhang C1, Huang JP1, Huang GH1, He J1.
To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for treating abdominal wall endometrioses (AWE).
A retrospective study.
Department of Obstetrics and Gynaecology in China.
Patients with abdominal wall endometriosis.
From August 2010 to April 2014, 32 patients with AWE were treated with USgHIFU in our hospital. USgHIFU treatment was performed with the Model JC-200 High Intensity Focused Ultrasound Tumor Therapeutic System. The symptom relief and the adverse effects were evaluated after USgHIFU ablation.
MAIN OUTCOME MEASURES:
USgHIFU as a new treatment option for patients with AWE.
Contrast-enhanced ultrasound showed that all lesions were successfully ablated with USgHIFU. The follow-up results showed that the average volume of AWE lesions at 6 months after USgHIFU was significantly smaller than that before treatment (2.80 ± 0.12 versus 1.33 ± 0.31 cm3 ). The pain scores at 6 months after treatment were significantly lower than those before treatment (6.80 ± 2.64 versus 1.80 ± 0.3). The non-perfused volume (indicative of successful ablation) was measured in all patients immediately after treatment, ranging from 0.9 to 2.1 cm3 (median: 1.6 cm3 ), and the fractional ablation ranged from 87% to 100% (median: 94%). Local oedema was observed in these patients, lasting for 1-3 days only. No severe complications occurred during the follow-up period.
Based on our study, USgHIFU ablation is a safe and effective method for treating AWE.
As a non-invasive treatment technique, HIFU could be used to treat abdominal wall endometriosis.
BJOG. 2017 Aug;124 Suppl 3:53-58.
A comparison between high-intensity focused ultrasound and surgical treatment for the management of abdominal wall endometriosis.
Zhu X1, Chen L1, Deng X1, Xiao S1, Ye M1, Xue M1.
The aim of this study was to compare the therapeutic outcomes of high-intensity focused ultrasound (HIFU) and surgical treatment for abdominal wall endometriosis.
A retrospective study.
Gynaecological department of a teaching hospital in China.
Patients with abdominal wall endometriosis.
Among the 51 patients, 23 patients were treated with ultrasound-guided HIFU and 28 patients with surgery. Pain relief and the size change of the nodule after each management were evaluated 1, 3, 6 and 12 months after treatment, respectively. The hospital stay and blood loss were also compared.
MAIN OUTCOME MEASURES:
Difference between HIFU and surgical treatment for abdominal wall endometriosis.
No statistically significant differences were observed between the two groups in the pain relief in 1, 3, 6 and 12 months after treatment, respectively. The hospital stay was clearly shorter in the HIFU group than in the surgery group. Change in nodules was more remarkable in the group treated with surgery; no palpable nodules existed in most patients in the surgery group. HIFU had more advantages over surgery, such as no blood loss, no new scar, no anaesthesia and lower pain score immediately after treatment.
Based on our results, it appears that either HIFU or surgery is safe and effective in treating patients with AWE in short-term. Compared with surgery, HIFU treatment for AWE has the advantages of shorter hospital stay, no blood loss, no new scar, no anaesthesia and a lower immediate pain score.
Either HIFU or surgical treatment is safe and effective in treating patients with AWE. HIFU has the advantages of a less invasive procedure and shorter hospital stay.
J Sex Med. 2017 Sep;14(9):1133-1141.
Different Characteristics of the Female Sexual Function Index in a Sample of Sexually Active and Inactive Women.
Hevesi K1, Mészáros V2, Kövi Z3, Márki G4, Szabó M5.
The Female Sexual Function Index (FSFI) is a widely used measurement tool to assess female sexual function along the six dimensions of desire, arousal, lubrication, orgasm, satisfaction, and pain. However, the structure of the questionnaire is not clear, and several studies have found high correlations among the dimensions, indicating that a common underlying “sexual function” factor might be present.
To investigate whether female sexual function is best understood as a multidimensional construct or, alternatively, whether a common underlying factor explains most of the variance in FSFI scores, and to investigate the possible effect of the common practice of including sexually inactive women in studies using the FSFI.
The sample consisted of 508 women: 202 university students, 177 patients with endometriosis, and 129 patients with polycystic ovary syndrome. Participants completed the FSFI, and confirmatory factor analyses were used to test the underlying structure of this instrument in the total sample and in samples including sexually active women only.
The FSFI is a multidimensional self-report questionnaire composed of 19 items.
Strong positive correlations were found among five of the six original factors on the FSFI. Confirmatory factor analyses showed that in the total sample items loaded mainly on the general sexual function factor and very little variance was explained by the specific factors. However, when only sexually active women were included in the analyses, a clear factor structure emerged, with items loading on their six specific factors, and most of the variance in FSFI scores was explained by the specific factors, rather than the general factor. University students reported higher scores, indicating better functioning compared with the patient samples.
The reliable and valid assessment of female sexual function can contribute to better understanding, prevention, and treatment of different sexual difficulties and dysfunctions.
STRENGTHS AND LIMITATIONS:
This study provides a rigorous statistical test of the structure of the FSFI and an explicit decision rule for categorizing sexually inactive women. Limitations include a lack of control over the circumstances of data collection.
This study supports the use of the FSFI as a multidimensional measurement of female sexual function but highlights the need to establish clear decision rules for the inclusion or exclusion of sexually active and inactive respondents. Hevesi K, Mészáros V, Kövi Z, et al. Different Characteristics of the Female Sexual Function Index in a Sample of Sexually Active and Inactive Women. J Sex Med 2017;14:1133-1141.
Cannabis Cannabinoid Res. 2017 Apr 1;2(1):72-80.
The Clinical Significance of Endocannabinoids in Endometriosis Pain Management.
Bouaziz J1,2, Bar On A1,2, Seidman DS1,2, Soriano D1,2.
Introduction: Patients with endometriosis often suffer from diffuse and poorly localized severe pain. The current pain management strategies include medical and hormonal therapy, as well as surgery. Medical management of pain is often insufficient and is associated with high rate of recurrence. Better pain management is therefore of urgent need. Methods: Among the various candidates, the endocannabinoid system (ECS) has recently emerged as a relevant pharmacological target for the management of endometriosis-related pain. A computerized literature search was performed to identify relevant studies combining the keywords “endometriosis,” “endocannabinoid,” “cannabinoid receptor,” “THC,” and “pain mechanisms.” Conclusions: This review describes the multiple and complex pain mechanisms associated with endometriosis. Current data and theories concerning the link between the ECS and pain management for endometriosis patients are presented. Finally, we will discuss which aspects of endometriosis-associated pain can be targeted by modulation of the ECS.
Fertil Steril. 2017 Oct;108(4):687-693.
Maternal endometriosis and genital malformations in boys: a Danish register-based study.
Arendt LH1, Lindhard MS2, Henriksen TB2, Forman A3, Olsen J4, Ramlau-Hansen CH5.
- [Fertil Steril. 2018]
To investigate the association between maternal endometriosis and occurrence of the genital anomalies cryptorchidism and hypospadias in sons.
Population-based cohort study.
All live-born singleton boys born from 1978 to 2012.
MAIN OUTCOME MEASURE(S):
Cryptorchidism and hypospadias in boys based on information from the Danish National Patient Register.
The study included 1,073,026 live-born singleton boys. A total of 6,443 boys were sons of women diagnosed with endometriosis before pregnancy. Altogether, 27,342 boys were diagnosed with cryptorchidism, of whom 16,446 had corrective surgery. Hypospadias was diagnosed in 4,853 boys. As compared with unexposed boys, a tendency towards a slightly higher occurrence of cryptorchidism was observed among boys of women with endometriosis (adjusted hazard ratio [aHR] 1.18; 95% confidence interval [CI], 0.97, 1.44). When stratified by medically assisted reproduction (MAR) technologies, the association was slightly stronger among boys born to women with endometriosis who had conceived via MAR, yet it remained moderate and statistically insignificant (aHR 1.27; 95% CI, 0.97, 1.70). When women who conceived with MAR were excluded, the association between endometriosis and cryptorchidism disappeared. For hypospadias, we observed no association, either in the main analysis or the stratified analysis.
The findings from this register-based study do not provide strong evidence for a higher occurrence of the studied genital anomalies among boys of women with endometriosis.
J Minim Invasive Gynecol. 2017 Aug 30.
Transvaginal Ultrasound for the Diagnosis of Adenomyosis: Systematic Review and Meta-Analysis.
Andres MP1, Borrelli GM1, Ribeiro J1, Baracat EC1, Abrão MS2, Kho RM3.
Adenomyosis is characterized by the presence of ectopic foci of endometrial glandular tissue and/or stroma within the myometrium. The diagnosis of adenomyosis is traditionally made through histologic evaluation of the postsurgical specimen. More recently, imaging with transvaginal ultrasound (TVUS) has been used for the preoperative diagnosis of adenomyosis. As yet, there is no consensus regarding the best imaging feature or combination thereof for the nonsurgical diagnosis of adenomyosis. This study systematically evaluated the literature in the last 10 years to determine the accuracy of 2-dimensional (2D) TVUS, different imaging features, enhancing methods such as 3-dimensional (3D) TVUS, elastography and color Doppler in the nonsurgical diagnosis of adenomyosis. A total of 8 studies were included. Pooled sensitivity and specificity for 2D TVUS for the diagnosis of adenomyosis for all combined imaging characteristics was 83.8% and 63.9%, respectively. Pooled sensitivity for 355 total patients with use of imaging feature of heterogeneous myometrium with 2D TVUS was highest (86.0%), and pooled specificity for 283 total patients with use of globular uterus was highest (78.1%). After including the “question mark” sign with other TVUS features, higher sensitivity and specificity, of 92% and 88%, respectively, were noted. For 3D TVUS, pooled sensitivity and specificity for all combined imaging characteristics was 88.9% and 56.0%, respectively. Poor definition of junctional zone showed the highest pooled sensitivity (86%) and the highest pooled specificity (56.0%) for the diagnosis of adenomyosis with 3D TVUS. There was no improvement in overall accuracy in 3D TVUS compared with 2D TVUS. Preliminary results of TVUS with color Doppler showed a high sensitivity and specificity for the differentiation between adenomyosis and myomas (95.6% and 93.4%, respectively). Also, TVUS elastography in 1 study showed an improvement in specificity (82.9%) compared with 2D TVUS (63.9%), albeit with comparable sensitivity. Larger studies are needed to advance our understanding of the different types of adenomyosis and their clinical impact.
Gynecol Obstet Fertil Senol. 2017 Sep;45(9):486-490.
Bowel endometriosis and infertility: Do we need to operate?
Bourdon M1, Santulli P2, Marcellin L3, Lamau MC4, Maignien C4, Chapron C3.
Endometriosis is a benign chronic inflammatory disease, whose pathogenesis is still unclear. Endometriosisis responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical: superficial peritoneal, ovarian and/or deep infiltrating lesions). Bowel involvement constitutes one particularly severe form of the disease, affecting 8-12% of women with deep endometriosis. In case of associated infertility, bowel endometriosis constitutes a real therapeutic challenge for gynecologists. Indeed, while complete resection of the lesions alleviates pain and seems to improve spontaneous fertility, surgery remains technically challenging and may cause severe complications. Reverting to assisted Reproductive Technology (ART) is another valuable therapeutic option regarding pregnancy rates. Thus, the choice between surgical management or ART is still debated. Benefits and risks of these two options should be considered and discussed before planning treatment. In the present study, we aimed to answer the question: Bowel endometriosis and infertility: do we need to operate?
Cancer Epidemiol Biomarkers Prev. 2017 Sep;26(9):1470-1473.
History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium.
Minlikeeva AN1, Freudenheim JL2, Eng KH3, Cannioto RA1, Friel G4, Szender JB5, Segal B6,7, Odunsi K5,8, Mayor P5, Diergaarde B9, Zsiros E8, Kelemen LE10, Köbel M11, Steed H12, deFazio A, Jordan SJ13, Fasching PA14,15, Beckmann MW15, Risch HA16, Rossing MA17, Doherty JA18, Chang-Claude J19,20, Goodman MT21, Dörk T22, Edwards R23,24, Modugno F23,24,25, Ness RB26, Matsuo K27, Mizuno M28, Karlan BY29, Goode EL30, Kjær SK31,32, Høgdall E31,33, Schildkraut JM34, Terry KL35,36, Cramer DW35,36, Bandera EV37, Paddock LE38,39, Kiemeney LA40, Massuger LFAG41, Sutphen R42, Anton-Culver H43,44, Ziogas A44, Menon U45, Gayther SA46,47, Ramus SJ48,49, Gentry-Maharaj A45, Pearce CL50,51, Wu AH51, Kupryjanczyk J52, Jensen A31, Webb PM13, Moysich KB53,2,7; Ovarian Cancer Association Consortium; Australian Ovarian Cancer Study Group.
Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470-3. ©2017 AACR.
Am J Case Rep. 2017 Sep 4;18:949-952.
Vesico-Adnexal Fistula Treated with Transurethral Embolization Under Fluoroscopic Guidance.
Al-Omari MH1, Hamid AS2.
BACKGROUND Vesico-adnexal fistulae are rare. Potential causes of such fistulae include infection, endometriosis, and iatrogenic causes following pelvic surgeries. To the best of our knowledge, only 3 cases of vesico-adnexal fistulae have been reported, and all these patients were treated surgically by removing the involved adnexa, excising the fistulous duct, and suturing the bladder. We describe the first case of vesico-adnexal fistula that developed after pelvic surgery, and it was successfully treated by transurethral embolization under fluoroscopic guidance. CASE REPORT Our patient was a 27-year-old woman with a history of hysterectomy. She presented to our institution with urethral discharge and a recurrent urinary tract infection. The cystogram showed a fistula tract connecting the urinary bladder and left adnexal cystic cavity. She was treated conservatively with antibiotics and prolonged Foley catheterization to allow for spontaneous closure of the fistula; however, conservative management failed. The patient was successfully treated with transurethral embolization of the tract under fluoroscopic guidance. CONCLUSIONS In such a rare scenario with limited treatment options, interventional radiology offers an alternative minimally invasive treatment strategy.
Int J Mol Cell Med. 2017 Winter;6(1):61-65.
Prenatal Diagnosis of Mosaic Tetrasomy 18p in a Case without Sonographic Abnormalities.
Karimzad Hagh J1, Liehr T2, Ghaedi H3, Mossalaeie MM1, Alimohammadi S4, Inanloo Hajiloo F1, Moeini Z1, Sarabi S1, Zare-Abdollahi D5.
Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they cannot be identified or characterized unambiguously by conventional cytogenetics alone. On the other hand, and perhaps more importantly in prenatal settings, there is a challenging situation for counseling how to predict the risk for an abnormal phenotype, especially in cases with a de novo sSMC. Here we report on the prenatal diagnosis of a mosaic tetrasomy 18p due to presence of an sSMC in a fetus without abnormal sonographic signs. For a 26-year-old, gravida 2 (para 1) amniocentesis was done due to consanguineous marriage and concern for Down syndrome, based on borderline risk assessment. Parental karyotypes were normal, indicating a de novo chromosome aberration of the fetus. FISH analysis as well as molecular karyotyping identified the sSMC as an i(18)(pter->q10:q10->pter), compatible with tetrasomy for the mentioned region. Cordocentesis was done due to normal sonography and the results from amniocentesis were confirmed. The parents opted for pregnancy termination and post mortem examination now noted, low anterior hairline, large philtrum, low-set posteriorly rotated malformed ears with prominent antihelix, lower limbs joint contracture and digital anomalies, including long and narrow toes with clinodactyly of the 1st and 5th toes and postaxial polydactyly of one hand. De novo i(18p) can be considered as a special case in the sense that the major relevant phenotypes mentioned for it, i.e. feeding difficulties, abnormalities in muscle tone and developmental/mental retardation, cognitive and behavioral characteristics, recurrent otitis media and seizures, are mostly postnatal. This emphasizes the necessity to determine the nature of a de novoeuchromatic marker chromosome, especially in cases with normal ultrasound result and the suitability of a cordocentesis in order to better predicting the pregnancy outcome and parental counseling.
Gynecol Endocrinol. 2018 Feb;34(2):148-152.
Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS).
Artimani T1, Karimi J2, Mehdizadeh M3, Yavangi M1, Khanlarzadeh E4, Ghorbani M1, Asadi S2, Kheiripour N2.
Chronic low-grade inflammation has been suggested as a key contributor of the pathogenesis and development of polycystic ovary syndrome (PCOS). To investigate the association between oxidative stress status and inflammatory cytokines in follicular fluid of 21 PCOS women compared to 21 women with normal ovarian function who underwent intra-cytoplasmic sperm injection. Concentration of IL-6, IL-8, IL-10, and TNF-α was measured using sandwich ELISA. Oxidative stress was examined by measuring total oxidant status (TOS), malondialdehyde (MDA), total antioxidant capacity (TAC), and thiol groups. PCOS women had an elevated concentration of MDA and TOS compared to controls. Levels of TAC and thiol groups were lower in PCOS compared to controls. PCOS patients had a higher concentration of IL-6, IL-8, and TNF-α compared to controls. Concentration of IL-10 was lower in PCOS compared to controls. Significant correlations were found between MDA and TOS concentration with TNF-α and between IL-6 and MDA, IL-8 and TAC, IL-10 and TOS levels and also between IL-10 and TAC levels. TAC and thiol groups were negatively correlated with TNF-α. Increased oxidative stress in PCOS is associated with inflammation which is closely linked. Inflammation can induce production of inflammatory cytokines in this syndrome and directly stimulates excess ovarian androgen production.
Gynecol Obstet Fertil Senol. 2017 Sep;45(9):472-477.
[Impact of osteopathic manipulative therapy in patient with deep with colorectal endometriosis: A classification based on symptoms and quality of life].
Daraï C1, Bendifallah S2, Foulot H3, Ballester M4, Chabbert-Buffet N4, Daraï E4.
A prospective study to evaluate the clinical impact of osteopathic manipulative therapy (OMT) on symptoms and quality of life (QOL) of patients with colorectal endometriosis.
Forty-six patients with colorectal endometriosis completed the SF-36 QOL and symptoms questionnaire before and after OMT. A comparison and clustering analysis was performed to identify subgroups of patient’s profile and symptom classification.
The mean age of the patients was 32±6.2 years. Prior surgery for endometriosis was recorded in 73.9 % of cases but none for deep infiltrating endometriosis. About three-quarters of the patients were nulliparous. The time between pre- and post-OMT completion of questionnaires was 28 days (15-63), A significant improvement in SF-36 QOL physical component summary (P<0.001) and mental component summary (P<0.001) was observed after OMT. Similarly, a significant improvement in gynecological, digestive and general symptoms values was observed. A clustering analysis allowed to identify four profiles of patients with colorectal endometriosis based on symptoms and a respective OMT gain of 30 %, 60 %, 64 % et 45 %.
Our results support that OMT improve QOL and endometriosis symptoms of patients with colorectal endometriosis. Moreover, this symptom classification based on OMT gain can serve to design future randomized trial.
Environ Int. 2017 Nov;108:195-203.
Associations between internal exposure levels of persistent organic pollutants in adipose tissue and deep infiltrating endometriosis with or without concurrent ovarian endometrioma.
Ploteau S1, Cano-Sancho G2, Volteau C3, Legrand A4, Vénisseau A5, Vacher V5, Marchand P5, Le Bizec B5, Antignac JP6.
Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue. Histologically, it appears as different sub-types, being peritoneal endometriosis, ovarian endometrioma (OvE) and deep infiltrating endometriosis (DIE), which are of major relevance due to their varying clinical presentations. A number of persistent organic pollutants (POPs) have been associated with the onset of endometriosis, yet the overall set of existing studies remains fairly divergent. In this preliminary case-control study we aimed to assess the potential associations between the internal exposure to POPs and the presence of DIE with or without concurrent OvE. Adipose tissue and serum samples were collected from surgically confirmed cases (n=55) and controls (n=44) enrolled during 2013 and 2015 in Pays de la Loire, France. Targeted pollutants (76 historical or more emerging POPs including dioxins, polychlorobiphenyls (PCB), polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), hexabromocyclododecanes (HBCDs) and organochlorine pesticides (OCPs) were quantified by chromatography coupled to mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated from unconditional logistic regression adjusted for known confounding variables. The results showed significant associations between DIE and adipose tissue levels of 126.96.36.199.8 – PeCDD, OCDF, PCB 105, 114, 118 and 123, PBDE 183, PBB 153, and several OCPs including trans‑nonachlor, cis‑heptachlor epoxide, dieldrin, β-hexachlorocyclohexane and hexachlorobenzene. The largest associations were observed for OCDF followed by cis‑heptachlor epoxide, exhibiting adjusted ORs (95% CI) of 5.42 (2.73-12.85) and 5.36 (2.44-14.84) per 1-SD increase, respectively. The stratified analysis comparing both disease sub-types suggested that adipose tissue exposure markers may be more associated with DIE concurrent with OvE, however these results need to be confirmed in a larger population.
Asian Pac J Trop Med. 2017 Jul;10(7):696-700.
Effect of Taoren Quyu Decoction on human endometrial cells and its anti-endometriosis activity in rats.
Liu HZ1, Han XX1, Liu J1, Zhu FC1, Li RM2.
To study the effect of Taoren Quyu Decoction (TQD) on endometrial cells in patients with endometriosis (EMs) and EMs in rats.
A total of 60 female Wistar rats were randomly divided into 4 groups, namely, normal group, model group, positive group and TQD group, each group having 15 rats. Except the normal group, EMs model was established in the other three groups by transplanting the rat autologous endometrium. After 4 weeks of intragastric administration, blood, eutopic and ectopic endometrial tissues of rats in each group were collected to detect the serum levels of estrogen (E2), cancer antigen 125 (CA125), endometrial antibody (EMAb), and expressions of microvessel density (MVD), vascular endothelial growth factor (VEGF) and angiopoietin (Ang-2). The volume of endometriosis cyst was determined simultaneously. For the in vitro culture of human endometrial cells, 4 groups, namely, normal group, model group, positive group and TQD group were used. The positive group and TQD group were treated with danazol and TQD respectively. Then 24 h after the treatment, the expressions of survivin and tumor suppressor gene (p53) of each group were detected.
The volumes of the endometriosis cysts in the positive group and the TQD group were significantly reduced compared with the model group (P < 0.05). The serum levels of E2, CA125 and EMAb, and the expressions of MVD, VEGF and Ang-2 in the model group were significantly increased compared with the normal group (P < 0.05); while they were all significantly reduced in the positive group and TQD group (P < 0.05). Compared with the normal group, the expression of survivin in the model group was significantly up-regulated (P < 0.05), and expression of p53 was significantly reduced (P < 0.05); compared with the model group, the expressions of survivin in the positive and TQD groups were significantly decreased (P < 0.05), and expression of p53 was significantly up-regulated (P < 0.05). The difference between positive group and TQD group was not statistically significant (P > 0.05).
TQD has a significant anti-EMs effect, and its mechanism of action may be related to anti-angiogenesis and promoting apoptosis of ectopic endometrial cell.
J Obstet Gynaecol Can. 2017 Sep 1.
Factors Associated with Severity of Irritable Bowel Syndrome Symptoms in Patients with Endometriosis.
Lee CE1, Yong PJ2, Williams C2, Allaire C2.
This study sought to examine factors associated with severity of irritable bowel syndrome (IBS) by using the Birmingham IBS symptom scale in patients presenting with endometriosis to a tertiary referral centre.
A prospective research cohort of patients presenting to a tertiary referral centre for endometriosis was evaluated for the presence and severity of IBS between December 2013 and April 2015. Patients with endometriosis had a diagnosis of IBS by using the Rome III criteria and were evaluated for severity of IBS symptoms by using the Birmingham IBS symptom scale. Multifactorial variables, including stage of endometriosis at the time of previous surgery, clinical examination findings, mood disorder questionnaire scores, and lifestyle factors, were evaluated using the t test and Spearman rank correlation test.
A total of 194 of 373 (52%) women with confirmed endometriosis had a diagnosis of IBS. Factors associated with severity of IBS symptoms in patients with endometriosis included lower-stage endometriosis(P = 0.004), presence of mood disorders (P <0.001), tenderness on physical examination (P ≤ 0.001), a history of sexual assault (P ≤ 0.02), and presence of sleep disturbance (P ≤ 0.01). Evaluation of the subscales of the Birmingham IBS symptom scale revealed a strong association between the previously identified factors and the pain subscale.
Using the Birmingham IBS symptom scale, our study revealed more severe IBS symptoms in patients with lower-stage endometriosis and identified other variables highly associated with severity of IBS. Continued research is required to characterize further the clinical importance of IBS symptoms in patients with endometriosis-associated pelvic pain.
Gynecol Obstet Invest. 2017 Sep 6.
The Endometriosis Fertility Index Is Useful for Predicting the Ability to Conceive without Assisted Reproductive Technology Treatment after Laparoscopic Surgery, Regardless of Endometriosis.
Hobo R, Nakagawa K, Usui C, Sugiyama R, Ino N, Motoyama H, Kuribayashi Y, Inoue M, Sugiyama R.
The endometriosis fertility index (EFI) is a novel index for predicting pregnancy after surgery. We investigated the utility of the EFI for predicting the ability to conceive without assisted reproductive technology (ART) treatment after laparoscopic surgery.
From July 2011 through December 2012, we recruited 133 infertile patients who underwent laparoscopy, and the EFI was calculated. After surgery, 55 of 133 achieved pregnancy without ART treatment. We evaluated the factors that predicted a naturally successful pregnancy and compared them between the pregnant and non-pregnant subjects.
On a univariate linear regression analysis, we found that a younger age, shorter duration of infertility, and higher EFI were positively associated with a successful pregnancy without ART after laparoscopic surgery (p < 0.05). According to 50th percentile EFI, the cutoff EFI predicting a successful pregnancy without ART was 7, the pregnancy rate in the high-EFI group (EFI; 8-10) was significantly higher than that in the low-EFI group (EFI ≤7; p < 0.05), but the duration to natural conception after surgery was similar between the 2 groups.
The EFI possesses greater predictive power for a successful pregnancy with natural intercourse or intrauterine insemination in infertile patients, regardless of endometriosis, than the Revised-American Society of Reproductive Medicine classification.
Reprod Sci. 2018 Jan;25(1):19-25.
18F-Fluorocholine Uptake and Positron Emission Tomography Imaging in Rat Peritoneal Endometriosis.
Silveira MB1, Rodrigues DM2, Araújo MR1, Santiago MA2, Gonçalves NT2, Schirmer BGA1, Carneiro MM2, Reis FM2, Malamut C1, Ferreira MC2.
Endometriosis is a debilitating disease that still needs surgery to be confirmed. Endometriosis is associated with increased plasma levels of phosphatidylcholines. 18F-fluorocholine ([18F]FCH) is a radiopharmaceutical that is metabolized to phosphatidylcholine inside the cells and can be traced by positron emission tomography (PET). Here we evaluate [18F]FCH as a potential tool for the noninvasive diagnosis of peritoneal endometriosis. Adult female Wistar rats had autologous uterine fragments dissected and grafted to the peritoneal wall to model peritoneal endometriosis. Ex vivo biodistribution assay and PET imaging studies were performed 30 minutes after [18F]FCH administration. The [18F]FCH uptake was 3-fold higher in endometriotic implant tissues than in muscle or peritoneum. Positron emission tomography imaging revealed the grafted uterine tissue in contrast to surrounding structures. Region-of-interest analysis of the reconstructed images showed higher accumulation of [18F]FCH by endometriotic lesions, 0.34 (0.04)% of injected dose per gram of tissue (ID/g), in comparison with muscle tissue, 0.08 (0.01)% ID/g. However, sham implants with fat tissue were also detectable in PET imaging. These preliminary findings of [18F]FCH uptake by ectopic uterine tissue implants and their localization by PET imaging encourage the future evaluation of this technique to detect small superficial endometriosis lesions in humans. Study protocols need to be further perfected and adapted for tests in women with endometriosis.
Fertil Steril. 2017 Oct;108(4):667-672.e5.
Endometriosis and obstetrics complications: a systematic review and meta-analysis.
Zullo F1, Spagnolo E2, Saccone G1, Acunzo M3, Xodo S4, Ceccaroni M5, Berghella V6.
To evaluate the effect of endometriosis on pregnancy outcomes.
Systematic review and meta-analysis.
Women with or without endometriosis.
Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included.
MEAN OUTCOME MEASURE(S):
Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI).
Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia.
Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.
Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Horm Mol Biol Clin Investig. 2017
Bowel endometriosis: a diagnostic and therapeutic challenge.
Ng BK1, Phon SE1, Zainuddin AA1, Ng WYL1, Abd Shukor N1, Lim PS1.
Bowel endometriosis is the most common extragenital manifestation of endometriosis. Clinical suspicion is of utmost importance for achieving its diagnosis. Management of this condition is, however, always challenging to the gynaecologist. We report a case of bowel endometriosis in which the patient presented with dyschezia and haematochezia prior to her menses for the past 2 years. A 44-year-old para two woman presented with worsening dysmenorrhea and dyspareunia. She also experienced dyschezia and haematochezia prior to her menses for the past 2 years. An examination revealed a fixed retroverted uterus. A computed tomography scan showed focal bowel thickening. She underwent a colonoscopy examination and biopsy that revealed stromal endometriosis. She was subsequently treated with dienogest and became asymptomatic. Diagnosis and management of this debilitating illness was revisited and discussed.
Eur J Obstet Gynecol Reprod Biol. 2017 Oct;217:101-105.
Is endometrioma-associated damage to ovarian reserve progressive? Insights from IVF cycles.
Benaglia L1, Castiglioni M2, Paffoni A3, Sarais V3, Vercellini P2, Somigliana E3.
The relation between endometriomas and damage to ovarian reserve remains controversial. In this study, we hypothesized that this damage may not be present at the time of endometrioma formation but may conversely gradually develop over time.
To investigate the possibility of a time-related detrimental effect of endometriomas on ovarian reserve, we retrospectively selected 29 women with unilateral cysts who underwent at least two IVF cycles at least 6 months apart and evaluated ovarian responsiveness over time. Women were excluded if they conceived, developed new endometriomas or necessitated new medical or surgical therapies for endometriosis during the interval between the two cycles, RESULTS: The mean±SD of the diameter of the endometriomas was 26±8mm. Most women (n=25) had only one endometrioma. In the first cycle, the number of developing follicles in the affected and contralateral intact gonads was 4.9±2.5 and 5.9±2.4, respectively (p=0.10). In the second cycle, it was 5.0±2.9 and 6.0±2.8, respectively (p=0.13). The median (Interquartile Range) proportion of follicles developing in the affected ovaries in the first and second cycles was 44% (31-58%) and 44% (35-55%), respectively (p=0.97). Subgroup analyses according to the duration of the time interval between the two assessments, the dimension of the endometriomas and the history of previous surgery for endometriosis did not show subgroups at significant risk of time-related damage.
We failed to observe an endometrioma-related reduction of ovarian responsiveness with time. However, evidence from larger series obtained in women carrying larger cysts and enrolled for longer time period of time are required for a definitive conclusion.
Eur J Obstet Gynecol Reprod Biol. 2017 Oct;217:106-112.
New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study.
Sobalska-Kwapis M1, Smolarz B2, Słomka M1, Szaflik T3, Kępka E4, Kulig B3, Siewierska-Górska A4, Polak G5, Romanowicz H2, Strapagiel D6, Szyłło K3.
Endometriosis is a common gynaecological disease, associated with severe pelvic pain and reduced fertility; however, molecular mechanisms remain largely unknown. Genome-wide association studies (GWAS) are able to identify genetic loci, which can play significant role during endometriosisdevelopment.
The study aimed at localisation of new genes and chromosomal loci, the nucleotide variants of which determine the level of susceptibility to endometriosis.
Blood samples from 171 patients with endometriosis were used as material for studies. The patients were recruited to the study at the Department of Operative Gynaecology of the Institute of the Polish Mother’s Memorial Hospital in Lodz. A control group (n=2934) came from the POPULOUS collection registered at Biobank Lab, Department of Molecular Biophysics, University of Lodz. DNA of the patients with endometriosis was compared with DNA of women free from that disease, the comparison being supported by GWAS.
Genome-wide significant correlation was identified between one new, not previously described, single nucleotide polymorphism (SNP), rs10129516, localised on chromosome 14 in intergenic region between PARP1P2 and RHOJ genes (p=1.44×10-10, OR=3.104, 95% CI=2.329-4.136) and endometriosis. We have also identified significant association with endometriosis of 18 SNPs localised on chromosome 6 in position range 31883957 – 32681631 (C2 and HLA-DRA genes region) with the lowest observed p value for rs644045 in C2 gene (p=2.04×10-8, OR=1.955, 95% CI=1.541-2.480).
Reported GWAS identified the novel loci associated with endometriosis in Polish women, not previously reported. The most interesting observation shown in our study are regions associated with susceptibility to endometriosis of loci located near C2, HLA-DRA and RHOJ genes.
of that study did not correspond to previously published data about polymorphism in that regions and further evaluations are necessary in groups with higher numbers of patients to explain whether the above-mentioned genetic variant may be the risk factor for pathogenesis of endometriosis.
Copyright © 2017 Elsevier B.V. All rights reserved.
BMJ Open. 2017 Sep 7;7(9):e017216.
Rectal water contrast transvaginal ultrasound versus double-contrast barium enema in the diagnosis of bowel endometriosis.
Jiang J1, Liu Y1, Wang K1, Wu X1, Tang Y1.
The aim of study was to compare the accuracy between rectal water contrast transvaginal ultrasound (RWC-TVS) and double-contrast barium enema (DCBE) in evaluating the bowel endometriosispresence as well as its extent.
DESIGN AND SETTING:
198 patients at reproductive age with suspicious bowel endometriosis were included. Physicians in two groups specialised at endometriosis performed RWC-TVS as well as DCBE before laparoscopy and both groups were blinded to other groups’ results. Findings from RWC-TVS or DCBE were compared with histological results. The severity of experienced pain severity through RWC-TVS or DCBE was assessed by an analogue scale of 10 cm.
In total, 110 in 198 women were confirmed to have endometriosis nodules in the bowel by laparoscopy as well as histopathology. For bowel endometriosis diagnosis, DCBE and RWC-TVS demonstrated sensitivities of 96.4% and 88.2%, specificities of 100% and 97.3%, positive prediction values of 100% and 98.0%, negative prediction values of 98.0% and 88.0%, accuracies of 98.0% and 92.4%, respectively. DCBE was related to more tolerance than RWC-TVS.
RWC-TVS and DCBE demonstrated similar accuracies in the bowel endometriosisdiagnosis; however, patients showed more tolerance for RWC-TVS than those with DCBE.
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bowel endometriosis; diagnosis; double-contrast barium enema; rec
In Vivo. 2017 Sep-Oct;31(5):999-1002.
Ileocecal Obstruction Due to Endometriosis – A Case Report and Literature Review.
Bacalbasa N1, Balescu I2, Filipescu A1,3.
Endometriosis is a common finding in premenopausal women and a significant number of cases presenting digestive tract involvement at the time of diagnosis. However, most of these patients present pelvic nodules involving the rectosigmoidian junction, other digestive tract segments being less commonly affected. We present the case of a 37-year-old nulliparous woman who presented for diffuse abdominal pain and vomiting; she was diagnosed with complete ileocecal obstruction due to an endometriosis nodule in association with bilateral ovarian endometriosis lesions invading the rectosigmodian wall. A right colectomy with ileocolic anastomosis in association with bilateral cystectomy and rectosigmodian resection was successfully performed. The histopathological examination confirmed the endometriosic origin of the nodules invading the rectosigmodian and ileocecal wall, that was similar to the one described at the level of the ovarian cysts.
Am J Obstet Gynecol. 2017 Sep 6.
Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment.
Oladosu FA1, Tu FF1, Hellman KM2.
Although nonsteroidal antiinflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well-studied strategies. The goal of this review is to provide a background for treating menstrual pain when first-line options fail. Research on menstrual pain and failure of similar drugs in the antiplatelet category suggested potential mechanisms underlying nonsteroidal antiinflammatory drug resistance. Based on these mechanisms, alternative options may be helpful for refractory cases. This review also identifies key pathways in need of further study to optimize menstrual pain treatment.
J Minim Invasive Gynecol. 2017 Sep 6.
Direct Mass Spectrometry Differentiation of Ectopic and Eutopic Endometrium in Patients with Endometriosis.
Adamyan L1, Starodubtseva N2, Borisova A1, Stepanian A3, Chagovets V1, Salimova D1, Wang Z4, Kononikhin A2, Popov I2, Bugrova A1, Chingin K4, Kozachenko A1, Chen H4, Frankevich V1.
To introduce a method for the rapid assessment of endometriotic tissues using direct mass spectrometry (MS)-based lipidomics.
A prospective observational cohort study (Canadian Task Force classification II2).
Department of Operative Gynecology of the Research Centre for Obstetrics, Gynecology and Perinatology.
Fifty patients with ovarian cysts and peritoneal endometriosis who underwent laparoscopic surgery between 2014 and 2016.
Differences in mass spectrometric profiles of ectopic endometria (endometriosis) and eutopic endometria were analyzed for each patient in combination with morphohistologic evaluation. The lipidomic approach was applied using a direct high-resolution MS method.
MEASUREMENTS AND MAIN RESULTS:
Of 148 metabolites, 15 showed significant differences between endometriotic tissue and a healthy endometrium of the same patient, considered as a control in this study. The main lipids prevalent in endometriotic tissues were phosphoethanolamine (PE O-20:0), sphingomyelin (SM 34:1), diglycerides (DG 44:9), phosphatidylcholines (PC 32:1, PC O-36:3, PC 38:7, PC 38:6, PC 40:8, PC 40:7, PC 40:6, PC 40:9, and PC O-42:1), and triglycerides (TG 41:2, TG 49:4, and TG 52:3). Using partial least squares discriminant analysis models, MS showed that the lipidomic profile of endometriotic tissue (peritoneal endometriosis and ovarian endometriomas) was clearly separated from the eutopic endometrium, indicating tissue-type differentiation.
Our results suggest that direct MS may play an important role for endometriotic tissue identification. Such an approach has potential usefulness for real-time tissue determination and differentiation during surgical treatment. Lipids of 3 important classes, sphingolipids, phospholipids, and the fatty acids (di- and triglycerides), were identified. Validation is required to determine whether these lipids can be used to discriminate between patients with endometriosis and those with other gynecologic diseases.
Reprod Toxicol. 2017 Dec;74:77-84.
Decreased zinc and increased lead blood levels are associated with endometriosis in Asian Women.
Lai GL1, Yeh CC2, Yeh CY1, Chen RY1, Fu CL1, Chen CH3, Tzeng CR4.
Endometriosis is an inflammatory disease associated with multiple pathogenic factors and studies regarding roles of trace metals in endometriosis have been inconsistent and limited. The aim of this cross-sectional study was to compare the blood levels of miscellaneous trace metals measured by inductively coupled plasma mass spectrometry in infertile women with and without endometriosis. Zinc level is associated with declining odds (adjusted OR=0.39, 95% CI=0.18-0.88) of endometriosis. By contrast, lead level is associated with increasing odds (adjusted OR=2.59, 95% CI=1.11-6.06) of endometriosis. The cadmium levels were higher in women with endometriosis, but the aOR was not significant. Zinc has anti-inflammatory characteristics and regulates homeostasis of zinc-containing superoxide dismutase. High lead levels might induce reactive oxygen species and deplete antioxidant defense mechanisms. Further prospective study is needed to test for their causal associations.
J Obstet Gynaecol Can. 2017 Sep 7.
Prevalence of Endometriosis and Its Symptoms among Young Jordanian Women with Chronic Pelvic Pain Refractory to Conventional Therapy.
Al-Jefout M1, Alnawaiseh N2, Yaghi S3, Alqaisi A4.
This study sought to explore the prevalence and clinical manifestations of endometriosis in young women with chronic pelvic pain (CPP) refractory to conventional medical therapy.
This prospective clinical interventional study was conducted in two general and private hospitals in the city of Al-Karak in Jordan. A total of 28 female patients aged ≤21 who had CPP refractory to conventional medical therapy were recruited during the years 2010-2014. The intervention used in the study was laparoscopy. Endometriosis was staged according to the American Society for Reproductive Medicine classification. The main outcome measures were the presence and stage of endometriosis at laparoscopy, the presence of cold intolerance, and the severity and duration of pain symptoms.
The mean age of participants was 18.4 (range 15 to 21). Endometriosis was found in 20 of 28 participants (71.4%), as follows: stage I, 9 of 20 (45.0%); stage II, 8 of 20 (40%); stage III, 2 of 21 (10%); and stage IV, 1 of 21 (5%). Notably, 16 of 28 (57.1%) of all participants reported cold intolerance, including 14 of 20 (70%) with endometriosis and 2 of 8 (25%) without endometriosis (Fisher exact [1-tail] P = 0.039). There was no association between stage of disease and age distribution (≤18 and >19 to 21; P = 0.7) or with duration of symptoms (≤2 and >2 years) and the presence of cold intolerance (P > 0.05). However, severity of pain symptoms (<7 vs. ≥7, as measured by the visual analogue scale [VAS]) was associated significantly with stage of disease (P = 0.011).
The prevalence of endometriosis among young women with CPP refractory to conventional therapy was high, mainly in the mild stage. Cold intolerance was highly associated with endometriosis.
Gynecol Surg. 2017;14(1):15.
The role of the multidisciplinary team in the management of deep infiltrating endometriosis.
Ugwumadu L1, Chakrabarti R1, Williams-Brown E1, Rendle J1, Swift I1, John B1, Allen-Coward H1, Ofuasia E1.
The multidisciplinary team (MDT) is considered good practice in the management of chronic conditions and is now a well-established part of clinical care in the NHS. There has been a recent drive to have MDTs in the management of women with severe endometriosis requiring complex surgery as a result of recommendations from the European Society for Human Reproduction and Embryology (ESHRE) and British Society for Gynaecological Endoscopy (BSGE). The multidisciplinary approach to the management of patients with endometriosis leads to better results in patient outcomes; however, there are potentially a number of barriers to its implementation and maintenance. This paper aims to review the potential benefits, disadvantages and barriers of the multidisciplinary team in the management of severe endometriosis.
Minerva Ginecol. 2017 Sep 5.
Does endometriosis influence the age of menopause?
Ottolina J1, Bartiromo L2, Viganò P3, Makieva S3, Schimberni M2, Candiani M2.
Endometriosis is an inflammatory disease affecting 7-10% of women throughout their reproductive life. Few data are available regarding the age at menopause of women affected by this disease. Most of the available evidence, although scanty, would indicate that both ovarian surgery for endometriomas and endometriosis”per se” appear to influence age at menopause. Other factors might interfere with the age at menopause of women affected by endometriosis. The purpose of this review is to examine the age at menopause in women with a history of endometriosis and to identify factors that might affect the timing of menopause.
Reprod Sci. 2017 Oct;24(10):1454-1461.
Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression: Potential Implications for Endometriosis.
Babayev SN1, Park CW1,2, Keller PW1, Carr BR1, Word RA1, Bukulmez O1.
Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression.
Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation.
As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation.
Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.
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