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Relationship between 17-beta-estradiol and prolactin in the regulation of natural killer cell activity during progression of endometriosis.

Endometriosis is an estrogen-dependent disease affecting women during their reproductive years. An abnormal immune function and, in particular, a decreased natural killer (NK) cell activity have been found in endometriosis, suggesting a role of the immune system in the pathophysiology of the disease. We have recently evidenced a significant inverse relationship between 17-beta-estradiol plasma levels and NK cytotoxicity in endometriosis patients. In this study we have investigated the combined role of 17-beta-estradiol (E2) and prolactin (PRL) in the regulation of NK cell activity during the progression of endometriosis, by evaluating the correlation among E2, PRL, and other immunomodulating neurohormones on both the cytotoxic activity and the number of NK cells in women at different stages of endometriosis. The early stages (I/II) of endometriosis are characterized by increased plasma levels of either E2 or PRL without significant alterations of NK cell activity in comparison with healthy subjects. The progression to advanced stages (III/IV) of the disease is associated with a further increase of E2 levels, a decrease of PRL plasma concentrations (with an increase of E2/PRL ratio), and an impairment of NK cytotoxicity. The plasma levels of both E2 and PRL and the E2/PRL ratio are significantly correlated with the values of NK cytotoxicity in advanced stages of endometriosis. Either the absolute number or the relative percentage of CD16+ or CD56+ peripheral lymphocytes are not significantly different between patients at either stages I/II or III/IV and healthy controls. Plasma levels of progesterone (P) and luteinizing hormone (LH), are not significantly changed in different stages of endometriosis with respect to healthy controls. The significant decrease of follicle-stimulating hormone (FSH) plasma levels found in either stages I/II or III/IV endometriosis patients is not correlated with the NK cell activity. In conclusion, at advanced stages of endometriosis the impairment of NK cell activity occurs with increased E2, and decreased PRL plasma levels. Additional studies are required to determine whether the E2/PRL ratio represents a possible biochemical marker of endometriosis.

Adult↗

High concentrations of the CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid between patients with and without endometriosis.

OBJECTIVE: In the present study we compared the levels of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid (PF) of patients with and without endometriosis, then assessed the possibility of a correlation among these tumor markers. STUDY DESIGN: Our study was a controlled clinical study of patients undergoing laparoscopy for infertility or other benign gynecology conditions. Peritoneal fluid samples were collected from 65 women with endometriosis and 43 women without pelvic disease. Levels of CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid were determined by immunoradiometric assay. RESULTS: The concentration of CA-125 in PF from patients with endometriosis was significantly higher than that in the control group (p<0.001); for CA 19-9 and CA 15-3, PF concentrations were not statistically different between these two groups. Women with endometriosis had significantly higher levels of CA-125 in proliferative and secretory phases than the control group (p<0.001 and p<0.002 respectively); furthermore, in patients with endometriosis the CA 19-9 levels were significantly lower in secretory phase than the proliferative (p<0.004). The levels of CA-125 were significantly lower in women with tubal ligation, in comparison with infertility or pelvic pain in the control group (p<0.001). No significant difference was seen in women with infertility or pelvic pain in endometriosis group and the levels of CA-125, CA 19-9, and CA 15-3. We did not find any correlation between the stages of endometriosis and the concentration of CA-125, CA 19-9 and CA 15-3. A significant correlation between the CA 19-9 levels and CA 15-3 in patients with endometriosis was found (r=0.72, p=0.001). CONCLUSIONS: We found high concentrations of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid of women with and without endometriosis in the Yale series. However, the levels only of CA-125 were higher in women with endometriosis, but without diagnostic value. The role of simultaneously high concentrations of CA 19-9 and CA 15-3 in women with endometriosis needs to be explored further.

Adult↗

Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis.

OBJECTIVE: Women with endometriosis may be at an increased risk of ovarian cancer. It is not known whether reproductive factors that reduce the risk of ovarian cancer in general also reduce risk in women with endometriosis. We investigated whether the odds ratios for ovarian cancer that were associated with oral contraceptive use, childbearing, hysterectomy, and tubal ligation differ among women with and without endometriosis. STUDY DESIGN: We pooled information on the self-reported history of endometriosis from 4 population-based case-controlled studies of incident epithelial ovarian cancer, comprising 2098 cases and 2953 control subjects. We obtained data on oral contraceptive use, childbearing, breastfeeding, gynecologic surgical procedures, and other reproductive factors on each woman. Multivariable unconditional logistic regression was used to calculate odds ratios and 95% CI for ovarian cancer among women with endometriosis compared with women without endometriosis. Similar methods were used to assess the frequencies of risk factors among women with and without endometriosis. Adjustments were made for age, parity, oral contraceptive use, tubal ligation, family history of ovarian cancer, and study site. RESULTS: Women with endometriosis were at an increased risk of ovarian cancer (odds ratio, 1.32; 95% CI, 1.06-1.65). Using oral contraceptives, bearing children, and having a tubal ligation or hysterectomy were associated with a similar reduction in the odds ratios for ovarian cancer among women with and without endometriosis. In particular, the use of oral contraceptives for >10 years was associated with a substantial reduction in risk among women with endometriosis (odds ratio, 0.21; 95% CI, 0.08-0.58). CONCLUSION: Women with endometriosis are at an increased risk of epithelial ovarian cancer. Long-term oral contraceptive use may provide substantial protection against the disease in this high-risk population.

Adult↗

Association of endometriosis with body size and figure.

OBJECTIVE: To determine whether body size and perceived figure, both current and historical, are associated with a diagnosis of endometriosis on laparoscopy. DESIGN: Cohort study of consecutively identified patients undergoing laparoscopy for tubal sterilization or as a diagnostic procedure. SETTING: Two university-affiliated hospitals. PATIENT(S): A cohort of 84 women aged 18-40 years. Endometriosis was visualized in 32 cases; 52 women (controls) had no visualized endometriosis, including 22 undergoing tubal sterilization and 30 with other gynecologic pathology. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Body mass index (BMI, kg/m2) from self-report and perception of body figure were compared for their ability to predict case status (diagnosed endometriosis), using logistic regression models. Longitudinal trends in BMI based on perceived figure at 5-year intervals from age 15 years were compared using mixed linear models. RESULT(S): Based on self-report, women diagnosed with endometriosis were taller, thinner, and had a significantly lower BMI. In this series, cases were more likely to be late maturers (menarche at > or = 14 y) and late to initiate sexual activity (> or = 21 y), and they were less likely to be gravid, parous, and a current smoker. Adjusting for age (in years), being tall (height > or = 68 in), and parity (yes vs. no), a higher current BMI was statistically protective for a diagnosis of endometriosis, regardless of whether BMI was determined by self-report (adjusted odds ratio [AOR] = 0.88, 95% confidence interval [CI] 0.79-0.99) or from perceived figure (AOR = 0.86, 95% CI 0.75-0.99). For every unit increase in BMI (kg/m2), there was an approximate 12%-14% decrease in the likelihood of being diagnosed with endometriosis. In an adjusted repeated measures model, BMI was 21.3 +/- 0.6 kg/m2 (estimate +/- SE) for women with endometriosis, compared with 23.2 +/- 0.4 kg/m2 for the controls, a difference over all ages of -1.9 +/- 0.8 kg/m2. This is a consistent difference of about 10 lb at every age, assuming an average height of about 64.5 in. CONCLUSION(S): In a laparoscopy cohort, women diagnosed with endometriosis were found to have a lower BMI (leaner body habitus), both at the time of diagnosis and historically. That women diagnosed with endometriosis may have a consistently lean physique during adolescence and young adulthood lends support to the suggestion of there being an in utero or early childhood origin for endometriosis.

Adolescent↗

Endometriosis and the appendix: a case series and comprehensive review of the literature.

OBJECTIVE: To report the prevalence of appendiceal disease in women with chronic pelvic pain undergoing laparoscopy for possible endometriosis, summarize the literature, and more accurately estimate the prevalence of endometriosis of the appendix. DESIGN: Prospective case series and literature review. SETTING: Academic research institute. PATIENT(S): One hundred thirty-three patients with chronic pelvic pain and possible endometriosis undergoing laparoscopy. INTERVENTION(S): History, physical exam, and abdominopelvic laparoscopy. Endometriosis and adhesions were excised using selective Nd:YAG contact laser trabeculoplasty and pathologically evaluated. Only patients with visible abnormalities involving the appendix were treated via concurrent laparoscopic appendectomy. MAIN OUTCOME MEASURE(S): Appendiceal abnormalities at laparoscopy. RESULT(S): Of 133 patients, 13 had a previous appendectomy with unknown pathology. Of the remaining 120 patients, 109 reported right lower quadrant pain. Of this subgroup, six patients had appendiceal pathology: four with pathology-confirmed endometriosis, one with Crohn's disease suspected at laparoscopy, and one with chronic appendicitis. The prevalence of appendiceal endometriosis in patients with biopsy-proven endometriosis (n = 97) or with right lower quadrant pain (n = 109) was 4.1% and 3.7%, respectively. This rate was similar to the 2.8% prevalence confirmed by literature review in patients with endometriosis but was much higher than that reported in all patients (0.4%). CONCLUSION(S): Appendiceal endometriosis, while relatively uncommon in patients with endometriosis, is rare in the general population. In patients with right lower quadrant or pelvic pain, the appendix should be inspected for endometriosis and evidence of nongynecologic disease.

Adult↗

Expression of WT1 is down-regulated in eutopic endometrium obtained during the midsecretory phase from patients with endometriosis.

OBJECTIVE: To investigate whether WT1 protein expression is altered in eutopic endometrium of endometriosis patients. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with endometriosis and fertile women with macroscopically normal pelvic cavities. INTERVENTION(S): During surgery, endometrial tissues were obtained from 59 patients with deep infiltrating endometriosis, ovarian endometriosis, or only superficial peritoneal endometriosis. Control endometrial tissue samples were obtained from 40 fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. MAIN OUTCOME MEASURE(S): The percentage of nuclear surface positively immunostained for WT1 (PI) and WT1-positive microvessel density. RESULT(S): The PI was significantly lower in endometrial stromal cells from patients with deep infiltrating endometriosis than in stroma from control subjects during the midsecretory phase, whereas there was no significant difference between the two populations during the proliferative, early secretory, and late secretory phases. The PI was also significantly lower during the midsecretory phase in endometrial stromal cells from patients with ovarian endometriosis and superficial peritoneal endometriosis compared with control subjects. CONCLUSION(S): During the midsecretory phase, PI in endometrial stromal cells is down-regulated in patients with deep infiltrating endometriosis, ovarian endometriosis, and superficial peritoneal endometriosis compared with endometrium from healthy control subjects.

Down-Regulation↗

Vitamin D binding protein in endometriosis.

OBJECTIVE: Two-dimensional gel electrophoresis is a powerful method for identifying post-translationally modified molecules in biological fluids. We examined the presence and expression of vitamin D binding protein (DBP) in the peritoneal fluid (PF) and plasma (PL) of women with endometriosis. METHODS: PL and PF samples were obtained from 36 women with untreated mild endometriosis (revised classification of the American Fertility Society [rAFS] stage I-II), 52 women with untreated severe endometriosis (rAFS stage III-IV), 17 women with endometriosis treated with the oral contraceptive (OC), and 40 controls (infertility, n = 23; tubal sterilization, n = 12; pelvic pain, n = 5). PF and PL samples were analyzed by quantitative, high-resolution 2-dimensional gel electrophoresis. RESULTS: The expression of one DBP isoform (DBPE) in the PF of patients with untreated endometriosis was significantly lower than in the control group (P <.05). The levels of PF DBPE in patients with endometriosis using OC were significantly higher than in women with untreated endometriosis (P <.05). No significant difference was observed in PL DBPE expression between women with and without endometriosis, while it was significantly increased in patients with endometriosis using OC (P <.05). DBP expression was not correlated with the stage of endometriosis (rAFS classification) or the phase of the menstrual cycle. CONCLUSION: The decreased level of DBPE in the PF but not in PL of women with untreated endometriosis suggests that this molecule may be relevant in the pathogenesis of this disease.

Adult↗

Endometriosis: a stage by stage analysis--the role of in vitro fertilization.

OBJECTIVE: To investigate the impact of endometriosis stage on IVF. PATIENTS: A retrospective study of 214 patients diagnosed with endometriosis who underwent 360 cycles of IVF at The New York Hospital-Cornell Medical Center. Meanwhile, 111 pure mechanical (tubal) infertility patients treated in 160 cycles at the same time were designated as the control group for comparison. MAIN OUTCOME MEASURES: Patient's hormone and semen profiles, hormonal response and outcome to stimulation, as well as the outcome of pregnancy, abortion, and delivery rate were analyzed. RESULTS: No differences in the pregnancy outcome between the endometriosis and control groups were noted when compared among the subgroups of pure endometriosis, endometriosis plus tubal factor, endometriosis plus others (primarily endometriosis plus male factor), and control. Comparing the outcomes in pure endometriosis cases by staging, we could not find any discrepancies in terms of pregnancy rates (PRs) according to the severity of the disease. The addition of GnRH analogur down-regulation to gonadotropin stimulation resulted in an increase in PR. A relatively high delivery rate (38.9% per cycle, 41.9% per retrieval, and 43.2% per transfer) was achieved when the pure endometriosis patients were treated with concomitant leuprolide acetate down-regulation and gonadotropin. CONCLUSION: We have observed that pregnancy outcome in patients with endometriosis was not different than the outcome for patients with mechanical (tubal) infertility. There were no differences in PRs by stage of endometriosis.

Adult↗

The effect of endometriosis on implantation: results from the Yale University in vitro fertilization and embryo transfer program.

OBJECTIVE: To investigate the effect of endometriosis on implantation. DESIGN: Case-control study from Yale University IVF-ET program. PATIENTS: Two hundred eighty-four consecutive IVF cycles were analyzed retrospectively. Patients with endometriosis only (n = 35; 89 cycles) were compared with an age-matched control group with tubal infertility (n = 70; 147 cycles) and also to a group with unexplained infertility (n = 15; 48 cycles). Data from the endometriosis group was analyzed further in subgroups of minimal-mild (43 cycles) and moderate-severe (46 cycles). RESULTS: No difference was found in the number and the quality of oocytes retrieved and fertilization rates between the endometriosis, the tubal infertility, and the unexplained infertility groups. The quality and the number of embryos transferred in each group were comparable. A trend toward reduced pregnancy rate per transfer (14.8%) in the endometriosis versus tubal or unexplained infertility groups (25.7% and 23.3%, respectively) was observed. Implantation rate (gestational sac per transferred embryo) was significantly lower in the endometriosis versus the tubal infertility group (3.9% versus 8.1%; unexplained infertility group, 7.2%). Analysis of first cycles only across all groups revealed that the implantation rate also was significantly lower in the endometriosis versus the tubal infertility group (3.1% versus 9%; unexplained infertility group, 6.7%). Within the endometriosis group, although the pregnancy rate per cycle and per transfer were similar in subgroups, patients with minimal-mild endometriosis had the lowest implantation rate. CONCLUSION: We conclude that, in patients with endometriosis, implantation rate is low. Abnormal implantation, which may be secondary to endometrial dysfunction or embryotoxic environment, is a factor in endometriosis-associated subfertility.

Adult↗

Clinical relevance of the baboon as a model for the study of endometriosis.

OBJECTIVE: To review the value of the baboon as a model for the study of endometriosis. DATA IDENTIFICATION AND SELECTION: Studies performed at the Institute of Primate Research in Nairobi, Kenya (1990-1994), and published in peer-reviewed journals. RESULT(S): Spontaneous endometriosis was found in about 25% of the baboons, and its prevalence increased with the duration of captivity. The laparoscopic appearance, pelvic localization, and microscopic aspects of the disease were similar to endometriosis in women. Microscopic endometriosis in macroscopically normal peritoneum was rare. Sampson's hypothesis (i.e., retrograde menstruation causes endometriosis) was supported by the increased incidence of retrograde menstruation in baboons with spontaneous endometriosis, the observation that cervical occlusion could cause retrograde menstruation and endometriosis, and the finding that intrapelvic injection of menstrual endometrium caused experimental moderate to severe endometriosis similar to the spontaneous disease. During follow-up of more than 2 years, endometriosis in baboons appeared to be a progressive disease, with active remodeling between several types of lesions. Progression was stimulated by high-dose immunosuppression. Fertility was normal in baboons with minimal disease but was reduced in baboons with mild, moderate, or severe endometriosis, possibly related to an increased incidence and recurrence of the luteinized unruptured follicle syndrome. CONCLUSION(S): The baboon is a good model for the study of endometriosis.

Animals↗

Correlation between endometriosis-associated dysmenorrhea and the presence of typical or atypical lesions.

OBJECTIVE: To evaluate the correlation between the severity of endometriosis-associated dysmenorrhea and the extent of the disease assessed both with a current classification system and with the number and type of endometriosis lesions. DESIGN: Prospective, blinded study. SETTING: Tertiary care, university hospital. PATIENT(S): Sixty-five consecutive patients with endometriosis diagnosed at laparoscopy performed for pelvic pain, infertility, or adnexal mass. INTERVENTION(S): The patients were submitted preoperatively to a questionnaire including the assessment of the severity of dysmenorrhea by means of a 10-point linear analog scale. Evaluation of all visible signs of endometriosis at laparoscopy was performed by a surgeon not aware of the patients' symptoms. MAIN OUTCOME MEASURE(S): The correlation between the severity of dysmenorrhea and the total score for endometriosis and the partial scores for superficial, deep, and adhesion disease as assessed with a current classification system was evaluated. The severity of dysmenorrhea was also correlated with the total number of superficial implants and with the number of typical, pigmented versus atypical, nonpigmented lesions. RESULT(S): The linear analog score for dysmenorrhea correlated significantly with the total endometriosis score, the partial score for deep endometriosis, and the partial score for adhesions. There was no correlation between the pain score for dysmenorrhea and the partial score for superficial endometriosis, nor with the total number of endometriosis implants, the number of typical implants, or the number of atypical implants. CONCLUSION(S): The current classification system for endometriosis, devised primarily to formulate a prognosis in infertile patients, correlates significantly with endometriosis-associated dysmenorrhea. The present study does not support the suggested association between atypical implants and the severity of dysmenorrhea.

Adult↗

Ovarian atypical endometriosis: its close association with malignant epithelial tumours.

The incidence of ovarian atypical endometriosis and its association with malignant epithelial tumours in a consecutive series of cases during the period 1987 to 1995 were studied. Atypical glandular changes were observed in four (1.7%) of 255 ovarian endometriosis cases and one patient with ovarian atypical endometriosis developed subsequent endometrioid carcinoma in the abdominal wall. Fifty-four (24.1%) of the 224 ovarian cancers were associated with ovarian endometriosis; 21 with typical and 33 with atypical endometriosis. Clear cell carcinomas and endometrioid carcinomas were most frequently associated with endometriosis, with 54% (27 of 50 cases) and 41.9% (13 of 31), respectively. Atypical endometriosis was found in 18 clear cell carcinomas, in seven endometrioid carcinomas, in four serous carcinomas, in three mucinous borderline tumours, and in one serous borderline tumour. In 13 cases, the atypical endometriosis was in contiguity with malignant epithelial tumours. We consider that atypical endometriosis possesses a precancerous potential or is most frequently associated with clear cell and endometrioid carcinomas. Close screening of cellular atypia or hyperplasia in ovarian endometriosis and careful long-term follow-up of patients with atypical endometriosis is required.

Adult↗

The involvement of T lymphocytes in the pathogenesis of endometriotic tissues overgrowth in women with endometriosis.

BACKGROUND: Endometriosis, uncontrolled proliferation of ectopic and eutopic endometriotic tissues, is common in women at reproductive age, and may affect fertility. The role of macrophages in the pathogenesis is well proved, but engagement of T cells in the pathogenesis of endometriosis is a matter of controversy. AIMS: T-cell involvement in the pathogenesis of endometriosis was the objective of our study performed on women aged 24-46 years with diagnosed endometriosis. All the patients that were studied underwent diagnostic laparoscopy. METHODS: We evaluated the distribution of T-lymphocyte subpopulations in peripheral blood (PB), peritoneal fluid (PF) and in endometriotic tissues (ET), as well as cytokines [interleukin (IL)-2, IL-4, IL-10, IL-12, interferon (IFN)-gamma] production by peripheral blood lymphocytes. IFN-gamma, tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 were investigated for their intracellular presence. The experiments were carried out before and after 6 months treatment with the GnRH-Analogous Goserelin (Zeneca Pharmaceuticals). The number of performed investigations is presented. Statistical analysis was performed using Statistica/Win 5.0 software and Student's t-test, the paired Student t-test and Fisher's exact test when appropriate. RESULTS: We have compared the lymphocyte subset re-distribution with regard to the American Fertility Society (AFS) stages and scores, but no differences were observed. The significant increase in CD4:CD8 ratio, the decrease in the number of natural killer (NK) cells in PB and the decrease in CD4:CD8 ratio in PF and ET of women with endometriosis was noted. The diminished IFN-gamma secretion by phytohemagglutinim (PHA)-stimulated lymphocytes in vitro derived from women with endometriosis and increased IL-4 production may be responsible for defective immunosurveillance against overgrowth of endometriotic tissues. The diminished NK cells number in PB of women with endometriosis argues for such a hypothesis. The increased deposits of proinflammatory IL-6 and TNF-alpha in the T lymphocytes of women with endometriosis may be related to T-regulatory lymphocyte function and their inability to suppress cell proliferation in endometriosis. GnRH-Analogous Goserelin treatment normalises cytokine production and induces patient recovery. CONCLUSIONS: The significant functional and phenotypic differences between the lymphocytes from healthy women and women with endometriosis were noted. The diminished IFN-gamma production in relation to decreased NK cells number and the increased IL-4 production before the treatment and normalisation after the treatment suggest the involvement of the deregulated T-cell system in the growth stimulation and recruitment of endometriotic cells. The increased CD4:CD8 ratio, IL-6, TNF-alpha deposits and diminished anti-inflammatory IL-10 production by lymphocytes may participate in the pathogenesis of endometriosis, and may secondarily affect the monocyte/macrophage function.

Adult↗

Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study.

In 100 consecutive patients who were undergoing laparoscopy for infertility (group 1, n = 52), chronic pelvic pain (group 2, n = 18) or tubal sterilization (group 3, n = 30, asymptomatic fertile women), peritoneal biopsies were taken from areas of visually normal peritoneum of uterosacral ligaments. Twenty-six patients in group 1 (50%), eight patients in group 2 (44.4%) and 13 patients in group 3 (43.3%), were found to have laparoscopic evidence of endometriosis elsewhere in the pelvis. The majority of women (80.7% in group 1, 87.5% in group 2, and 100% in group 3) had stage I disease. The incidence of the distinctive appearances of the lesions was similar in the three groups of patients and 7% of all women or 15% (7/47) of those patients having endometriosis at laparoscopy had only subtle (non-¿typical') endometriotic peritoneal lesions. Uterosacral biopsies showed the presence of endometriotic tissue in three cases (5.7%), two cases (11%) and three cases (10%) in groups 1, 2, and 3 respectively. One of the two patients in group 2 and two of the three patients in group 3 had no evidence of endometriosis at laparoscopy; thus histological study revealed the presence of endometriosis in normal peritoneum in 11% (5/47) of patients having macroscopic endometriosis and in 6% (3/53) of patients without endometriosis at laparoscopy. Previous oral contraceptive users were significantly higher among women having macroscopic and/or microscopic endometriosis than among women without the condition. In conclusion, our prospective study shows a high prevalence (45-50%) of endometriosis (including microscopic forms) in both patients with chronic pelvic pain and asymptomatic women (fertile and infertile), thus supporting the modern concept that in many women endometriosis may be a paraphysiological condition while probably only in some patients small amounts of endometriosis are an ¿annoyance' with implications to their reproductive health and may produce symptoms (e.g. pelvic pain) and therefore should be defined as a ¿dis-ease'. Previous use of oral contraceptives may increase the risk of developing endometriosis.

Adult↗

Endometriosis is associated with an altered profile of intestinal microflora in female rhesus monkeys.

BACKGROUND: The intestinal microflora provide a strong defence against intestinal pathogens, and may be altered in inflammatory conditions that impact the gut, such as endometriosis. Therefore, intestinal bacteria shed from rhesus monkeys with endometriosis were compared with age-matched healthy controls. A second study assessed the prevalence of intestinal inflammation in female monkeys to determine whether endometriosis is associated with an increased likelihood of intestinal inflammation. METHODS: Differential and selective agars were used to enumerate total and Gram-negative aerobic and facultatively anaerobic bacteria, as well as Lactobacilli, from female monkeys with or without endometriosis. In addition, the prevalence of intestinal inflammation in monkeys with or without endometriosis was determined in a retrospective analysis of necropsy reports. RESULTS: Monkeys with endometriosis had a significantly different profile of shed microflora. Endometriosis was associated with lower Lactobacilli concentrations and higher Gram-negative bacteria concentrations. Moreover, there was a higher prevalence of intestinal inflammation in monkeys with endometriosis in comparison to healthy controls. CONCLUSIONS: Endometriosis is associated with an altered profile of intestinal microflora in rhesus monkeys. Although the exact mechanisms linking endometriosis and the microflora are unknown, it is possible that the microflora were affected by endometriosis-associated intestinal inflammation.

Animals↗

Clinical predictive factors for endometriosis in a Portuguese infertile population.

BACKGROUND: Endometriosis is an important clinical situation associated with subfertility. It would be very useful to identify patients at increased risk for endometriosis prior to laparoscopy. In the present study, we evaluate the demographic and clinical characteristics in a cohort of Portuguese subfertile women in relation to the presence of endometriosis. METHODS: Consecutive subfertile patients scheduled for laparoscopy were interviewed prior to the procedure. At subsequent laparoscopy, the presence of endometriosis was scored according to the revised classification of the American Society for Reproductive Medicine (ASRM). Data available from the medical history were tabulated against the presence or absence of endometriosis. We used logistic regression analysis to evaluate whether data from the patient's medical history could predict the presence of endometriosis. RESULTS: Among the 1079 women that were studied, 358 had minimal/mild endometriosis and 130 had moderate/severe endometriosis. Primary subfertility, regularity of menstrual cycles, dysmenorrhoea, chronic pelvic pain, obesity, ever use of oral contraceptives and smoking were the most important predictors of endometriosis. The prediction model had an area under the receiver operating characteristic curve of 0.71. CONCLUSIONS: Both the presence of endometriosis (all stages) and the presence of severe endometriosis per se can be predicted from the medical history. These data should be used in the decision to perform laparoscopy at an early stage or a later stage in the work-up for subfertility.

Chronic Disease↗

Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model.

BACKGROUND: Matrix metalloproteinases (MMPs) are essential for extracellular matrix remodelling and may contribute to the development of endometriosis. Transplantation of endometrium onto the chicken chorioallantoic membrane (CAM) results in endometriosis-like lesion formation, a process that requires extensive tissue remodelling. We investigated the expression of a wide range of MMPs in menstrual endometrium, endometriosis-like lesions in CAMs, in peritoneal endometriosis and in endometriosis in the rectovaginal space, as well as the function of MMPs in early lesion formation in the CAM model. METHODS: Expression of MMPs was evaluated by immunohistochemistry and MMP function was studied in the CAM by inhibiting MMP activity during lesion formation. RESULTS: Nearly all MMPs were present in all tissues studied. No significant differences in the expression of a majority of MMPs were found in endometriosis-like lesions in CAMs when compared with human endometriosis. Inhibition of MMP-1, -2, -3, -7 and -13 activities significantly impaired endometriosis-like lesion formation in CAMs. CONCLUSIONS: The MMP expression profiles of experimentally induced endometriosis in CAMs and human endometriosis are similar. The prevention of endometriosis-like lesion formation in the CAM by inhibiting MMP activity strongly suggests that MMPs have a function in the early development of endometriotic lesions.

Animals↗

Serum interleukin-6 levels are elevated in women with minimal-mild endometriosis.

BACKGROUND: There is a need for a reliable marker of endometriosis, especially in early stages of peritoneal disease during which imaging is not effective. The use of serum interleukin (IL)-6 as a marker is controversial. To readdress the matter, patients undergoing laparoscopy were prospectively evaluated for serum IL-6 levels. MATERIALS AND METHODS: A total of 119 women 31 years old who underwent laparoscopy were divided into groups: control patients (n = 38) with no pathologic findings; endometriosis sufferers (n = 47) with minimal-mild (MM, n = 11) or moderate-severe (MS, n = 36) endometriosis; uterine myomas (n = 13) and benign ovarian pathologies (n = 21). Blood was drawn on cycles days 5-12 and stored for subsequent analysis of IL-6 and carbohydrate antigen (CA)-125 levels. RESULTS: Serum IL-6 levels were significantly (P = 0.002) higher in women with MM endometriosis (29.4 9.0 pg/ml) than in controls (15.7 9.3 pg/ml). When all the non-endometriosis patients were grouped together (n = 72) and serum IL-6 (17.8 12.1 pg/ml) compared with MS (n = 36; 17.6 10.3 pg/ml) and MM (n = 11; 29.4 9.0 pg/ml) endometriosis significantly (P < 0.01) higher levels in MM endometriosis were observed as compared to the other two groups. Serum Ca-125 levels were significantly (P < 0.01) elevated in MS endometriosis. A serum IL-6 threshold of 25.75 pg/ml afforded a sensitivity of 75% and specificity of 83% in the diagnosis of MM endometriosis. Sensitivity and specificity for CA-125 in the diagnosis of MS endometriosis, using 35 IU/ml as the cut-off value, were 47% and 97%, respectively. CONCLUSIONS: IL-6 is a reliable non-invasive marker of MM endometriosis, whereas Ca-125 is of use as a marker of severe cases.

Adult↗