Electromyographic characterisation of abdominal wall trigger points developed after caesarean section and response to local anaesthesia: an observational study.

OBJECTIVE: This study examines the electromyography pattern of abdominal trigger points developed after a caesarean section, and the association between clinical response and local anaesthetic injection. DESIGN: Prospective cohort study. SETTING: A tertiary university hospital. POPULATION: Twenty-nine women with chronic pelvic pain associated with trigger points after a caesarean section were included in the study. METHODS: Participants received needle electromyography before treatment, then underwent a treatment protocol consisting of trigger-point injection of 2 ml of 1% lidocaine. The protocol was repeated once a week for 4 weeks. The clinical responses of the patients were compared 1 week after and 3 months after treatment. The clinical trial is registered with the Brazilian Clinical Trials Registry (REBEC) under RBR-42c6gz (www.ensaiosclinicos.gov.br/rg/RBR-42c6gz/). MAIN OUTCOME MEASURES: Needle electromyography and algometry results and pain reduction. RESULTS: Fifteen patients had abnormal electromyography findings; 14 had normal findings. The rates of response 1 week and 3 months after treatment within the abnormal electromyography group were 95 and 87%, respectively. In the normal group, the rate was 38% both 1 week after and 3 months after treatment. CONCLUSIONS: Trigger points developed after caesarean section, even without clinical symptoms or signs of neuralgia, may originate from neuropathies. Electromyographic abnormalities were associated with pain remission after anaesthesia injection; normal electromyography findings were associated with undiagnosed causes of pain, such as adhesions. TWEETABLE ABSTRACT: Trigger points developed after caesarean section are neuropathies, even in the absence of classical neuralgia.

Analysis of differential genetic expression in endometrial polyps of postmenopausal women.

OBJECTIVES: To evaluate the expression of four genetic markers (PTEN, BCL2, MLH1, and CTNNB1), linked to endometrial carcinogenesis, in endometrial polyps of patients with and without postmenopausal bleeding in order to determine whether symptomatic endometrial polyps have a genetic phenotype similar to that of endometrial cancer. METHODS: Samples were obtained hysteroscopically from endometrial polyps of postmenopausal patients, and the expression of genetic markers involved in the pathogenesis of endometrial cancer (PTEN, BCL2, MLH1, and CTNNB1) was analyzed. The expression of these markers was then compared between patients with and without symptoms, which was characterized as postmenopausal bleeding. Other clinical characteristics of the patients, such as duration of menopause, polyp size, presence of systemic hypertension, diabetes mellitus, and smoking habits were also analyzed. RESULTS: Samples from a total of 60 patients were obtained, as calculated for a test power of 0.80. No statistical differences (p > 0.05) were observed between the two groups concerning the expression of the studied endometrial cancer risk factor genes, or with regard to the clinical aspects evaluated. CONCLUSION: The study found no evidence that symptomatic endometrial polyps have a similar phenotype to type 1 endometrial cancer; further studies are needed in order to establish whether endometrial polyps are in fact true cancer precursors, or simply raise cancer incidence due to a detection bias.

Diagnosis of endometriosis in women with chronic pelvic pain.

PURPOSE OF INVESTIGATION: To assess the accuracy of CA-125 determination associated with clinical history and of the neutrophil/lymphocyte (N/L) ratio for a presumptive diagnosis of endometriosis in women with chronic pelvic pain (CPP). MATERIALS AND METHODS: This was a cross-sectional study of data from the medical records of women with CPP submitted to laparoscopy from August 1999 to January 2009 at the University Hospital. The performance of the evaluation of CA-125 and of the N/L ratio for the prediction of endometriosis was compared based on the corresponding ROC curves and their 95% confidence intervals. RESULTS: CA-125 levels were significantly higher in women with CPP and endometriosis and their association with a complaint of dysmenorrhea improved their sensitivity. For a cut-off of 20 IU/ml, the predictive value for a diagnosis of endometriosis in women with CPP was 97.6%. Dyspareunia, subfertility, and N/L ratio were not useful for a diagnosis of endometriosis in women with CPP. CONCLUSION: The association of elevated CA-125 levels with a complaint of dysmenorrhea is adequate in a presumptive and accurate diagnosis of endometriosis in this specific group of women with CPP, permitting an early institution of clinical treatment without the need of previous laparoscopic confirmation.

Serum markers of oxidative stress and endometriosis.

PURPOSE OF INVESTIGATION: To assess the changes secondary to chronic inflammation in women with and without pelvic endometriosis by the determination of serum thiols and carbonyls. MATERIALS AND METHODS: Sixty-seven women with endometriosis consecutively submitted to laparoscopy and 41 women without endometriosis consecutively submitted to tubal ligation (control group) were selected. Serum levels of total thiols and carbonyls were determined in both groups. RESULTS: Patients with endometriosis had significantly lower thiol levels than controls (342.37 +/- 142.09 microM vs 559.60 +/- 294.05 microM) (p < 0.001), as well as significantly lower carbonyl levels (8.97 +/- 3.76 microM vs 16.40 +/- 9.26 microM) (p < 0.001). Other clinical characteristics were not associated with changes in marker levels. The cutoff point established by the ROC curve was 396.44 microM for the thiols, with 73.1% sensitivity and 80.5% specificity, and 14.9 microM for the carbonyls, with 94% sensitivity and 51.2% specificity. CONCLUSIONS: The serum thiol levels revealed an increase in oxidative stress related to the development of pelvic endometriosis.

VIP expression in vessels of the vaginal wall: relationship with estrogen status.

OBJECTIVE: Vasoactive intestinal peptide (VIP) is a neuropeptide with elevated expression in regions that control urogenital functions. Estrogen appears to modulate VIP expression in various organs, but this effect has not been demonstrated in the vaginal wall. The aim of this study was to evaluate the influence of estrogen status on VIP expression in vessels of the vaginal wall. METHODS: Surgical specimens were removed from the vaginal walls of 18 premenopausal women and 12 postmenopausal women who were given surgery for genital prolapse grade I or II. Vaginal specimens were stained with estrogen receptor-alpha (ER-α) and VIP antibodies. Levels of follicle stimulating hormone (FSH), estradiol, prolactin, fasting glucose and serum thyroxine stimulating hormone were also measured. Estrogen status was assessed on the basis of FSH and ER-α scores. RESULTS: The vaginal walls of premenopausal women had significantly higher ER-α scores than those of menopausal women (premenopausal group, 3.6 ± 2.2; menopausal group, 1.4 ± 1.8; p = 0.01). Premenopausal women also had significantly higher levels of VIP in the vaginal wall than menopausal women (p = 0.02). Increasing age was associated with lower level of VIP staining (odds ratio 0.88; 95% confidence interval 0.78-0.99). CONCLUSION: Levels of ER-α and VIP expression in the posterior vaginal wall were higher in premenopausal than in menopausal women, but VIP expression was not associated with estrogen status. Age was an independent predictor of VIP staining in vaginal wall biopsies.

Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis.

The objective of this study was to evaluate the immunohistochemical expression of Dicer, Drosha, and Exportin-5 in the eutopic and ectopic endometrium of women with adenomyosis. Twenty-two paired ectopic and eutopic endometrium from women with adenomyosis and 10 eutopic endometrium samples from control women undergoing hysterectomy were included in the study. Paraffin-embedded tissue blocks were cut and stained for immunohistochemistry. The percentage of epithelial cells positively marked was identified digitally after an automated slide scanning process. Mann-Whitney test or Wilcoxon signed-rank test was performed for independent and paired groups, respectively. A lower expression of Drosha was observed in the eutopic endometrium of women with adenomyosis than in the eutopic endometrium of women without the disease (69.9±3.4% vs 85.2±2.9%, respectively) (P=0.016; 95%CI: 3.4 to 27.4%). We also detected lower Drosha expression in the ectopic endometrium of women with adenomyosis than in the eutopic endometrium of the same women (59.6±3.2% vs 69.9±3.4%, respectively) (P=0.004; 95%CI: 2.3 to 16.7%). Additionally, we observed a correlation between Drosha expression in the ectopic and paired eutopic endometrium (P=0.034, rho=0.454). No significant difference in Dicer or Exportin expression was observed. Predominant pattern of cytoplasmic staining for the anti-Drosha antibody and both a nuclear and cytoplasmic pattern for the anti-Exportin antibody were observed. Drosha expression was significantly lower in the endometrium of women with adenomyosis compared to the eutopic endometrium of asymptomatic women without the disease. Furthermore, its expression was lower in the ectopic endometrium but correlated to the paired eutopic endometrium.

Anti-müllerian hormone is the best predictor of poor response in ICSI cycles of patients with endometriosis.

PURPOSE: To correlate ovarian reserve (OR) markers with response in assisted reproduction techniques (ART) and determine their ability to predict poor response among patients with endometriosis (EDT). METHODS: We evaluated ART cycles of 27 women with EDT and 50 with exclusive male factor. Basal follicle stimulating hormone (FSH) and anti-müllerian hormone (AMH) levels were determined. Ovarian response to gonadotropin stimulation was assessed and correlation coefficients calculated between the variables and reserve markers. Areas under the curve (AUC) determined ability of tests to predict poor response. RESULTS: AMH was significantly correlated with response in both groups and it was the only marker with significant discriminative capacity to predict poor response among EDT (AUC = 0.842; 95% CI: 0.651-0.952) and control group (AUC = 0.869; 95% CI: 0.743-0.947). CONCLUSION: Infertile patients with endometriosis can benefit from the pre-therapeutic assessment of OR markers. However, regardless of disease presence, only AMH predicts poor response to stimulus.

Isolated osseous ovarian metaplasia: case report.

BACKGROUND: Some ovarian metaplasias may contain bone or osteoid tissue. The most common tumors presenting these alterations are teratomas and mixed mesodermal tumors with heterologous elements. CASE REPORT: We report the case of a woman who, during gynecologic follow-up for chronic anovulation at the age of 31 years, presented a solid ovarian ultrasonographic image with calcifications. After laparoscopy and histological examination it was found to be an isolated ovarian osseous metaplasia. CONCLUSION: A rarely occurring condition, ovarian osseous metaplasia continues to be of uncertain clinical significance.

Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium.

BACKGROUND: The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections. METHODS: Pre- and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n = 11) or GnRHa (n = 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor alpha (ER-alpha) were analyzed by immunohistochemistry. RESULTS: The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P < 0.05). Expression of ER-alpha and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P < 0.05). No difference was detected between groups for any of the markers. CONCLUSIONS: LNG-IUS reduced both cell proliferation and the expression of PRA and ER-alpha and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.

High levels of anxiety and depression have a negative effect on quality of life of women with chronic pelvic pain.

BACKGROUND: Chronic pelvic pain (CPP) is a common and complex disease whose cause is often clinically inexplicable, with consequent difficulty in diagnosis and treatment. Patients with CPP have high levels of anxiety and depression, with a consequent impairment of their quality of life. AIMS: The objective of this study was to determine the prevalence of anxiety and depression and their impact on the quality of life of women with CPP. MATERIALS AND METHODS: A cross-sectional controlled study was conducted on 52 patients with CPP and 54 women without pain. Depression and anxiety were evaluated by the Hospital Anxiety and Depression Scale, and quality of life was evaluated by the World Health Organization Quality of life Whoqol-bref questionnaire. Data were analysed statistically by the Mann-Whitney U-test, the Fisher exact test, chi-square test and Spearman correlation test. RESULTS: The prevalence of anxiety was 73% and 37% in the CPP and control groups, respectively, and the prevalence of depression was 40% and 30% respectively. Significant differences between groups were observed in the physical, psychological and social domains. Patients with higher anxiety and depression scores present lower quality of life scores. DISCUSSION: The fact that DPC is a syndromic complex, many patients enter a chronic cycle of search for improvement of medical symptoms. The constant presence of pain may be responsible for affective changes in dynamics, family, social and sexual. Initially the person is facing the loss of a healthy body and active, to a state of dependence and limitations. In this study, patients with higher scores of anxiety and depression scores had lower quality of life and patients with lower scores of anxiety and depression had scores of quality of life. These results show that perhaps the depression and anxiety may be related to the negative impact on quality of life of these patients. CONCLUSION: In view of this association, we emphasise the importance of a specific approach to the treatment of anxiety and depression together with clinical treatment to improve the quality of life of these patients.

Serological testing for celiac disease in women with endometriosis. A pilot study.

PURPOSE OF INVESTIGATION: Celiac disease (CD) involves immunologically mediated intestinal damage with consequent micronutrient malabsorption and varied clinical manifestations, and there is a controversial association with infertility. The objective of the present study was to determine the presence of CD in a population of infertile women with endometriosis. METHODS: A total of 120 women with a diagnosis of endometriosis confirmed by laparoscopy (study group) and 1,500 healthy female donors aged 18 to 45 years were tested for CD by the determination of IgA-transglutaminase antibody against human tissue transglutaminase (t-TGA) and anti-endomysium (anti-EMA) antibodies. RESULTS: Nine of the 120 women in the study group were anti-tTGA positive and five of them were also anti-EMA positive. Four of these five patients were submitted to intestinal biopsy which revealed CD in three cases (2.5% prevalence). The overall CD prevalence among the population control group was 1:136 women (0.66%). CONCLUSION: This is the first study reporting the prevalence of CD among women with endometriosis, showing that CD is common in this population group (2.5%) and may be clinically relevant.

Endometriosis in postmenopausal women without previous hormonal therapy: report of three cases.

INTRODUCTION: Endometriosis is a benign, estrogen-dependent, chronic gynecological disorder associated with pelvic pain and infertility. The disease most commonly affects women during the reproductive age, although postmenopausal patients do rarely present it. These rare occurrences are generally associated with hormonal use. MATERIAL AND METHODS: We present three cases of endometriosis in postmenopausal patients who have no history of hormone therapy and no previous history of endometriosis or infertility. CASE REPORTS: In case 1, a 62-year-old woman presented with acyclic pelvic pain and a left ovarian homogeneous cystic mass. After laparoscopic salpingoophorectomy and histological analysis, an ovarian endometriotic cyst was confirmed. In case 2, a 78-year-old woman presented with a painful abdominal wall mass that was confirmed by ultrasound and tomography. Her past medical history included an abdominal hysterectomy 20 years prior to the discovery of this mass. The lesion was surgically excised and histological analysis showed areas of endometrial stroma and glands surrounded by fibrosis, compatible with endometriosis. In case 3, a 54-year-old woman presented with chronic pelvic pain and a nodule in the rectovaginal septum was noted during gynecological examination. Menopause occurred at 48 years of age. She had no previous dysmenorrhea. Ultrasound confirmed the nodule in the rectovaginal septum. The patient was submitted to a diagnostic colonoscopy that revealed a friable lesion, which was subsequently biopsied. The histological diagnosis was endometriosis. CONCLUSIONS: These three cases of postmenopausal endometriosis support the celomic metaplasia theory for the genesis of this disease.

Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis.

Endometriosis is a benign, estrogen-dependent disease with symptoms such as pelvic pain and infertility, and it is characterized by the ectopic distribution of endometrial tissue. The expression of the ID2, PRELP and SMOC2 genes was compared between the endometrium of women without endometriosis in the proliferative phase of their menstrual cycle and the eutopic and ectopic endometrium of women with endometriosis in the proliferative phase. Paired tissue samples from 20 women were analyzed: 10 from endometrial and peritoneal endometriotic lesions and 10 from endometrial and ovarian endometriotic lesions. As controls, 16 endometrium samples were collected from women without endometriosis in the proliferative phase of menstrual cycle. Analysis was performed by real-time polymerase chain reaction (PCR). There was no significant difference between gene expression in the endometrium of women with and without endometriosis. The ID2 gene expression was increased in the most advanced stage of endometriosis and in ovarian endometriomas, the PRELP was more expressed in peritoneal lesions, and the SMOC2 was highly expressed in both peritoneal and endometrioma lesions. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue.

Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis

The objective of this study was to evaluate the immunohistochemical expression of Dicer, Drosha, and Exportin-5 in the eutopic and ectopic endometrium of women with adenomyosis. Twenty-two paired ectopic and eutopic endometrium from women with adenomyosis and 10 eutopic endometrium samples from control women undergoing hysterectomy were included in the study. Paraffin-embedded tissue blocks were cut and stained for immunohistochemistry. The percentage of epithelial cells positively marked was identified digitally after an automated slide scanning process. Mann-Whitney test or Wilcoxon signed-rank test was performed for independent and paired groups, respectively. A lower expression of Drosha was observed in the eutopic endometrium of women with adenomyosis than in the eutopic endometrium of women without the disease (69.9±3.4% vs 85.2±2.9%, respectively) (P=0.016; 95%CI: 3.4 to 27.4%). We also detected lower Drosha expression in the ectopic endometrium of women with adenomyosis than in the eutopic endometrium of the same women (59.6±3.2% vs 69.9±3.4%, respectively) (P=0.004; 95%CI: 2.3 to 16.7%). Additionally, we observed a correlation between Drosha expression in the ectopic and paired eutopic endometrium (P=0.034, rho=0.454). No significant difference in Dicer or Exportin expression was observed. Predominant pattern of cytoplasmic staining for the anti-Drosha antibody and both a nuclear and cytoplasmic pattern for the anti-Exportin antibody were observed. Drosha expression was significantly lower in the endometrium of women with adenomyosis compared to the eutopic endometrium of asymptomatic women without the disease. Furthermore, its expression was lower in the ectopic endometrium but correlated to the paired eutopic endometrium.

Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis.

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (µM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Cesarean section as a cause of chronic pelvic pain.

OBJECTIVE: To determine if the history of cesarean section was associated with chronic pelvic pain, independent of the presence of other conditions such as pelvic adhesions, endometriosis, sequelae of pelvic inflammatory disease, leiomyoma and pelvic varices. METHODS: Retrospective case-control study conducted on 199 patients consecutively admitted from January 1998 to January 2000, 116 of them submitted to laparoscopy for the diagnosis of chronic pelvic pain and 83 asymptomatic patients submitted to tubal ligation by laparoscopy. A logistic regression analysis was used to verify the association between chronic pelvic pain and the history of previous cesarean section. RESULTS: In women with chronic pelvic pain, a history of cesarean section was observed in 67.2% of cases, adhesions in 51.7%, endometriosis in 33.6%, sequelae of pelvic inflammatory disease in 31.9%, leiomyoma in 6.9% and pelvic varices in 11.2%. In asymptomatic women, a history of cesarean section was observed in 38.5%, adhesions in 24.1%, endometriosis in 9.6%, sequelae of pelvic inflammatory disease in 4.8%, leiomyoma in 7.2% and pelvic varices in 3.6%. In a logistic model, chronic pelvic pain was associated with a history of cesarean section (O.R.=3.7), as well as with endometriosis (O.R.=8.5), sequelae of pelvic inflammatory disease (O.R.=10.5). CONCLUSIONS: In the present study cesarean section was associated with chronic pelvic pain. This fact may be the cause of a public health problem in the coming years, due to the raised rates of cesarean section in Brazilian women.