Expression of cyclooxygenase-2 in eutopic endometrium and ovarian endometriotic tissue in women with severe endometriosis.

BACKGROUND/AIMS: The purpose of this study is to evaluate the level and pattern of cyclooxygenase-2 (Cox-2) expression in endometriosis and to investigate the correlation between the expression of Cox-2 and several clinicosurgical parameters. METHODS: Twenty-six patients with endometriosis and 21 patients with other benign gynecological conditions were enrolled. The eutopic endometrium was sampled by pipelle, and fragments of ovarian endometrioma and non-endometriotic ovarian cysts were sampled during surgery. Total RNA isolation and semiquantitative reverse transcriptase polymerase chain reaction was performed. RESULTS: The expression of Cox-2 mRNA (mean +/- SEM) in eutopic endometrium and ovarian endometriotic tissue significantly increased in patients with endometriosis compared with the controls. The expression of Cox-2 increased significantly in the proliferative phase in eutopic endometrium and in the secretory phase in ovarian endometriotic tissue of patients with endometriosis compared with the controls. Cox-2 mRNA expression in the endometrium and ovarian lesions significantly correlated with serum CA-125 and the diameter of the endometrioma. CONCLUSIONS: Cox-2 expression increased in the eutopic endometrium and ovarian endometriotic tissue of the patients with endometriosis. These findings indicate that Cox-2 may be involved in the pathogenesis and progression of endometriosis.

Bone mineral density, arterial stiffness, and coronary atherosclerosis in healthy postmenopausal women.

OBJECTIVE: The aim of this study was to assess the correlation between bone mineral density (BMD), arterial stiffness, and coronary atherosclerosis in healthy postmenopausal women. METHODS: We performed a retrospective review of 152 postmenopausal women who visited the health promotion center for a routine checkup, after excluding participants who had factors affecting BMD and coronary artery disease. BMD was evaluated by dual-energy x-ray absorptiometry in the lumbar spine and femur. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), and coronary atherosclerosis was assessed by 64-row multidetector computed tomography. RESULTS: Women with osteoporosis had a significantly higher baPWV than those in the osteopenia and normal BMD groups. Higher baPWV was also associated with the presence of atherosclerosis. The baPWV was significantly positively correlated with age, systolic blood pressure, diastolic blood pressure, and neutrophil to lymphocyte ratio and negatively correlated with femur BMD. The optimum predictive value of baPWV in coronary atherosclerosis was estimated using the receiver operating characteristic curve. A cutoff of 1,506 cm/second would give a sensitivity of 83.3% and specificity of 82.9%. A higher overall risk for coronary atherosclerosis emerges with higher baPWV levels (>1,500 cm/s) after controlling for age and cardiovascular risk factors. CONCLUSIONS: Arterial stiffness by measuring baPWV can be a useful independent predictor for coronary atherosclerosis. In addition, our results suggest that postmenopausal women with osteoporosis should be considered for further evaluation of coronary atherosclerosis.

Endometrial osteopontin mRNA expression and plasma osteopontin levels are increased in patients with endometriosis.

PROBLEM: The aim of this study was to evaluate osteopontin (OPN) mRNA expression in eutopic endometrium and plasma OPN levels in patients with endometriosis. METHOD OF STUDY: A total of 79 patients with histologically confirmed endometriosis and 43 patients without endometriosis participated in this study. OPN mRNA expression in endometrial tissues was measured by real-time quantitative polymerase chain reaction (PCR) and plasma concentrations of OPN were quantified using a specific commercial sandwich enzyme-linked immunosorbent assays (ELISA). RESULTS: Osteopontin mRNA expression in endometrial tissue was significantly higher in women with endometriosis than in controls (P = 0.010). The mean plasma levels of OPN (mean +/- S.E.M.) in patients with endometriosis and controls were 407.31 +/- 37.80 ng/mL and 165.84 +/- 19.29 ng/mL, respectively (P < 0.001). Receiver operating characteristic (ROC) analysis for plasma OPN revealed an area under the curve (AUC) of 0.894, with a sensitivity of 93.0%, specificity of 72.4%, positive likelihood ratio of 3.37, and negative likelihood ratio of 0.1 using a cut-off value of 167.68 ng/mL. CONCLUSION: Osteopontin may be involved in the pathogenesis of endometriosis and plasma OPN may be a useful non-invasive marker for the diagnosis of endometriosis.

Implication of ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 in implantational remodeling of a mouse uterus.

In the present study, whether the ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 proteins might play a role in mouse uterus during periimplantation period was investigated. Immunoblotting analyses demonstrated that all ADAM proteins consistently appeared throughout days 1 to 8 of pregnancy but with a variation depending on the species of ADAM gene, the progression of pregnancy, and the site of the uterus. Immunohistochemical analyses indicated that ADAM proteins were localized in the luminal or glandular epithelial layers with a varying intensity depending on the species of ADAM and the progression of pregnancy. Particularly ADAM-8, -12, and -15, were predominantly located in the implantation site of the uterine tissues, whereas little or no protein was localized in the interimplantation site. Based upon these observations, it is suggested that the ADAMs might play an important role in the remodeling of the mouse uterus during the periimplantation period.

Hysteroscopic endometrial ablation as a treatment for abnormal uterine bleeding in patients with renal transplants.

STUDY OBJECTIVE: To assess the effectiveness and safety of hysteroscopic endometrial ablation as a surgical management of abnormal uterine bleeding that develops in patients with renal transplants. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Yonsei University Medical College, Severance Hospital. PATIENTS: Sixty-two women with abnormal uterine bleeding who had undergone renal transplantation. INTERVENTION: Hysteroscopic endometrial ablation. MEASUREMENTS AND MAIN RESULTS: Fifty-four out of 62 patients (87.0%) who had undergone hysteroscopic endometrial ablation reported decreased bleeding (95% CI: 0.76 to 0.94): amenorrhea in 25 (40.3%), spotting in 19 (30.6%), and eumenorrhea in 10 (16.1%). Mean follow-up duration was 6 months. No complications related to the procedure were reported. Levonorgestrel-releasing intrauterine systems (LNG-IUSs) were inserted into eight patients who experienced continuous bleeding, five of whom showed symptomatic improvement: spotting in three (4.9%) and eumenorrhea in two (3.2%). The three patients (4.9%) in whom the LNG-IUS had no effect had hysterectomies, and the resultant pathologic findings were two cases of adenomyosis and one case of simple endometrial hyperplasia without atypia. CONCLUSION: Hysteroscopic endometrial ablation as a surgical management of abnormal uterine bleeding that develops in patients with renal transplants is an effective and safe procedure.

Expression of integrins, cyclooxygenases and matrix metalloproteinases in three-dimensional human endometrial cell culture system.

The objective of this investigation was to establish a three-dimensionally cultured human endometrium which could be used as a tissue model for the mechanism study of implantation in vitro. By using human endometrial stromal (ES) and epithelial cells (EE) from hysterectomy specimens, reconstruction of endometrium in culture was established by first layering a collagen gel containing ES cells, then overlaying with the Matrigel containing endometrial epithelial (EE) cells. Ultrastructural examination of the 48 h-endometrial cell culture revealed monolayered columnar EE cells with microvilli on the collagen layer containing ES cells and appearance of the tight junctions and desmosomes between EE cells, a cell layer closely resembling the native endometrium. Immunohistochemical characterization of the reconstructed endometrium showed a strong immunoreactivity for cytokeratin, integrin alpha1, alpha4 and beta3 subunits, cyclooxygenases-1 and -2, matrix metalloproteinases-1, -2, -3 and -9, and tissue inhibitor of metalloproteinases-1 and -2 in the EE cells comparable to the native endometrial epithelium. ES cells also showed stronger immunoreactivity for cyclooxygenases, integrins and MMPs, but less for cytokeratin. Gelatin zymographic analyses of the media obtained from the reconstructed endometrium model showed gelatinase activity bands at 57, 60, 72, 92 and 97 kDa molecular weight, respectively. The present study provides a possibility that our three-dimensionally cultured endometrium model could mimic the morphological and functional characteristics of the native endometrium. The model could be used to clarify the roles of various molecules involved in the human implantation.

Endometriosis in an adolescent population: the severance hospital in Korean experience.

The records of adolescent patients (10-21), who were admitted to the severance hospital between 1990 and 1999, were reviewed retrospectively to evaluate the age distribution, diagnosis, clinical stage, and treatment for endometriosis in adolescents. Thirty-nine patients who had undergone a laparotomy or laparoscopy and were diagnosed with endometriosis were identified. Endometriosis was classified according to the revised American Fertility Society classification (AFS). The chief symptoms leading to the diagnosis, clinical stage, age distribution, and treatment modality were reviewed. All patients, whose average age of menarche was 14.2, were diagnosed with endometriosis with an average interval of 5.9 years after menarche. The chief symptoms leading to the diagnosis were chronic pelvic pain (27%), acute pelvic pain (21%), a palpable pelvic mass (21%), and dysmenorrhea (18%). A laparoscopy was performed in 20 (51%). The majority of patients (44%) presented with the revised AFS classification stage II. Four patients (10%) presented with stage I, 11 (28%) with stage III and 7 (18%) with stage IV. Management after surgery included GnRH agonists (64.1%), expectant managements (25.7%), OCPs (5.1%) and danazol (5.1%). In adolescents with chronic pelvic pain, endometriosis is not rare. Therefore, early referral to a gynecologist to diagnose the etiology of the pelvic pain and initiate appropriate therapy is recommended.