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PubMed2000

Increase in the expression of killer cell inhibitory receptors on peritoneal natural killer cells in women with endometriosis.

OBJECTIVE: Malfunction of peritoneal natural killer cells (NK) may result in endometriosis. The present study was designed to determine whether the decrease in NK cytotoxicity occurs at early and advanced stages of endometriosis and is due to the increase in the NK inhibition receptors. DESIGN: A case control study. SETTING: A tertiary-care infertility center . PATIENT(S): A total of 44 women (controls, n = 11; women with early-stage endometriosis, n = 11; and women with advanced-stage endometriosis, n = 22) were included in this study. INTERVENTION(S): Laparoscopic examination. MAIN OUTCOME MEASURE(S): NK cytotoxicity was determined by assay of (51)Cr release against K562 cells, and the expression of killer cell inhibitory receptors (KIR, including NKB1, GL183, and EB6) in NK cells was examined by flow cytometry. RESULT(S): Women with endometriosis showed a decrease in peritoneal NK cytotoxicities against K562 at early and advanced stages of endometriosis. The expression of KIR (NKB1 and EB6) was significantly elevated in the peritoneal NK cells of women with advanced-stage endometriosis compared with controls. KIR (NKB1) was also significantly increased in peritoneal NK cells of women with advanced-stage endometriosis, compared with those of women with early-stage endometriosis. CONCLUSION(S): The results of this study suggest that the decrease in peritoneal NK cytotoxicities against K562 is observed and that this disease may be partially due to the increased expression of KIR on these NK cells.

Ascitic Fluid↗
PubMed2001

Women who are not exposed to spermatozoa and infertile women have similar rates of stage I endometriosis.

OBJECTIVE: To compare the prevalence of endometriosis and its different stages in infertile women and women not exposed to spermatozoa. DESIGN: Prospective study. SETTING: Artificial insemination donor program at a university hospital. PATIENT(S): One hundred fifty women unable to conceive because they had not been exposed to spermatozoa (134 with azoospermic partner, 10 with an HIV-positive partner, and 6 without a male partner). Controls were 750 women in infertile couples in which the male partner had normal sperm. INTERVENTION(S): Laparoscopy was systematically performed in a blinded manner in both groups as part of the infertility work-up. MAIN OUTCOME MEASURE(S): Diagnosis of endometriosis. RESULT(S): In unexposed women and controls, the prevalence of endometriosis was similar (32% and 34.5%). Rates of stage I disease were also similar in both groups (26% and 19.3%). There was a significant trend toward higher stages of endometriosis in infertile women (stage II disease, 3.3% vs. 5.7%; stage III disease, 1.3% vs. 3.1%; stage IV disease, 1.3% vs. 6.4%). Endometriosis was not associated with the few demographic characteristics that differed between groups. CONCLUSION(S): From an epidemiologic point of view, stage I endometriosis is not more common in infertile women than in unselected women. However, stage II to IV endometriosis was more frequent in infertile women. Whereas a relation between stage I endometriosis and infertility seems unlikely, the relation between stages II to IV endometriosis and infertility seems possible.

Adult↗
PubMed2002

Use of serum-soluble intercellular adhesion molecule-1 as a new marker of endometriosis.

OBJECTIVE: To investigate the hypothesis that soluble intercellular adhesions molecule-1 (sICAM-1) may be used as a new serum marker of endometriosis. DESIGN: Prospective cohort study. SETTING: An academic department specializing in gynecologic laparoscopy. PATIENT(S): Consecutive series of 120 women of reproductive age who underwent laparoscopy for benign gynecologic conditions. INTERVENTION(S): Data were collected on baseline clinical characteristics, and surgical and histologic diagnosis. MAIN OUTCOME MEASURE(S): Serum concentration of both CA125 and sICAM-1. RESULT(S): Endometriosis was documented in 71 women (stage I to II in 24 cases and stage III to IV in 47 cases). Serum levels of sICAM-1 were only slightly but not significantly increased in women with endometriosis compared with women without the disease. However, serum concentration of sICAM-1 in the 21 women who were found to have deep peritoneal endometriosis was significantly enhanced when compared with both women without the disease and those with other forms of endometriosis. The sensitivity and specificity of sICAM-1 in detecting deep peritoneal endometriosis were 0.19 and 0.97, respectively; whereas those of CA125 were 0.14 and 0.92, respectively. When both parameters were used concomitantly, the sensitivity and specificity were 0.28 and 0.92, respectively. CONCLUSION(S): Although the present study tends to support a role of sICAM-1 in the development of endometriosis, serum concentrations of this molecule do not seem to be an effective indicator for the diagnosis of either the early or advanced stage of endometriosis. However, an integrated clinical and laboratory approach using both CA125 and sICAM-1 may be helpful in specifically identifying women with deep peritoneal endometriosis.

Biomarkers↗
PubMed2003

Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis.

OBJECTIVE: To evaluate the utility of fat-suppressed magnetic resonance imaging (MRI) in the diagnosis of endometriosis. DESIGN: A prospective clinical trial. SETTING: A government research hospital. PATIENT(S): Forty-eight women with pelvic pain. INTERVENTION(S): Magnetic resonance imaging followed by surgical excision and pathologic diagnosis of endometriosis. MAIN OUTCOME MEASURE(S): Presence and extent of endometriosis suggested by preoperative MRIs compared with surgical inspection and biopsy. RESULT(S): A preoperative MRI in 46 women detected fewer endometriosis lesions than histopathology or laparoscopy (78 vs. 101 vs. 150). Few MRI lesions correlated with those identified by laparoscopy (50 of 150) or pathology (38 of 101). Of 42 women with surgically diagnosed endometriosis, 28 had at least one corresponding abnormality on MRI, 5 had abnormalities that didn't correlate with surgical findings, and 9 had normal MRIs. The sensitivity of MRI in detecting biopsy-proven endometriosis for any woman was 69% (25 of 36), and the specificity was 75%. CONCLUSION(S): Although MRI identifies fewer areas of endometriosis than seen at surgery, it suggested endometriosis in 75% of those with at least mild disease. Only 67% of lesions identified at surgery contained histologic evidence of endometriosis.

Adult↗
PubMed1998

Spontaneous apoptosis of endometrial tissue is impaired in women with endometriosis.

OBJECTIVE: To evaluate spontaneous apoptosis in single-cell suspensions of eutopic and ectopic endometrium from women with endometriosis and in eutopic endometrium from fertile controls without endometriosis. DESIGN: Paired specimens of eutopic and ectopic endometrial tissue from patients with endometriosis and eutopic endometrium from controls were assessed for spontaneous apoptosis. SETTING: Institute for the Study and Treatment of Endometriosis and university-based research laboratories. PATIENT(S): Fertile controls (n = 10) and women with untreated endometriosis (n = 16). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Spontaneous apoptosis assessed with an ELISA-based cell death detection kit. RESULT(S): Spontaneous apoptosis (monitored by absorbance) of eutopic endometrium from patients with endometriosis and fertile controls was 0.63 +/- 0.1 and 1.43 +/- 0.11, respectively. Among patients with endometriosis, spontaneous apoptosis of ectopic endometrium was 0.26 +/- 0.06. Decreased apoptosis of ectopic versus eutopic endometrium was observed independent of cycle phase. CONCLUSION(S): The susceptibility of endometrial tissue to spontaneous apoptosis is significantly lower in women with endometriosis than in fertile controls. We suggest that decreased susceptibility of endometrial tissue to apoptosis contributes to the etiology or pathogenesis of endometriosis.

Apoptosis↗
PubMed1998

The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production.

OBJECTIVE: To assess the endocrine, paracrine, and autocrine milieu in patients with endometriosis on the basis of the measurement of several cytokines in serum and follicular fluid (FF) and in vitro culture of granulosa luteal cells. DESIGN: Case-control study. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad. PATIENT(S): Twenty patients with laparoscopically documented endometriosis and 18 controls. Fifteen subjects were studied in a natural cycle and 23 were investigated in a stimulated cycle while undergoing IVF. INTERVENTION(S): Individual follicle aspiration, oocyte isolation, FF storage, and preparation of luteinized granulosa cell cultures. Diagnostic laparoscopy in natural cycles. MAIN OUTCOME MEASURE(S): Serum (day of ovum pick-up or laparoscopy) and FF measurement of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF). Secretion of IL-1beta, IL-6, and VEGF in the cell-conditioned medium. Results were compared between patients with endometriosis and controls. RESULT(S): Interleukin-6 levels in serum were increased in the natural cycles of patients with endometriosis and modulated by ovarian stimulation, showing a significant decrease in hMG- and FSH-stimulated cycles and a significant increase after hCG administration. In addition, IL-6 levels were increased in the FF of patients with endometriosis and released in higher amounts by their granulosa luteal cells. Vascular endothelial growth factor was accumulated in lesser concentrations in the FF of patients with endometriosis. Interleukin-1beta levels did not show significant changes. Implantation rates were decreased significantly in patients with endometriosis who were undergoing IVF. CONCLUSION(S): The data demonstrate that cytokines are regulated differently in patients with endometriosis, who have increased IL-6 production, and suggest that fine hormonal modulation of this cytokine occurs at the systemic and local (ovarian) levels. These changes show that the endocrine, paracrine, and autocrine milieu is different in patients with endometriosis and may be related to their lower implantation rates.

Adult↗
PubMed1999

Autoantibodies to markers of oxidative stress are elevated in women with endometriosis.

OBJECTIVE: To measure autoantibodies that recognize oxidatively modified proteins in the sera of women with surgically proven endometriosis. DESIGN: Prospective study. SETTING: Tertiary care academic medical center. PATIENT(S): Women undergoing surgery for endometriosis or tubal ligation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum and peritoneal fluid autoantibody titers to malondialdehyde-modified low-density lipoprotein, oxidized low-density lipoprotein, and lipid peroxide-modified rabbit serum albumin determined by ELISA. Correlation of autoantibody titers with revised American Fertility Society staging classification, symptoms, and morphologic type of endometriosis. RESULT(S): Mean (+/-SEM) serum autoantibody titers (in optical density units) to the three antigens were as follows: [1] lipid peroxide-modified rabbit serum albumin, 0.49 +/- 0.12 units in the patients with endometriosis and 0.2 +/- 0.02 units in the controls; [2] oxidized low-density lipoprotein, 0.22 +/- 0.005 units in the patients with endometriosis and 0.18 +/- 0.006 units in the controls; and [3] malondialdehyde-modified low-density lipoprotein, 0.21 +/- 0.005 units in the patients with endometriosis and 0.16 +/- 0.003 units in the controls. There was no correlation between autoantibody titers and revised American Fertility Society stage, symptoms, or morphologic type of endometriosis. Peritoneal fluid did not contain autoantibodies to any of the three antigens. CONCLUSION(S): Autoantibodies to markers of oxidative stress were significantly increased in women with endometriosis. These findings strongly support our data demonstrating that women with endometriosis have enhanced oxidative stress.

Adolescent↗
PubMed2003

Evidence for asymmetric distribution of sciatic nerve endometriosis.

OBJECTIVE: To investigate if a lateral asymmetry exists in the distribution of endometriotic lesions of the sciatic nerve. DATA SOURCES: All articles on sciatic nerve endometriosis identified by MEDLINE and EMBASE database searches were retrieved, and additional reports were collected by systematically reviewing all references. Monographs on endometriosis published in the last 15 years were consulted. METHODS OF STUDY SELECTION: We considered articles in which the presence of an endometriotic lesion of the sciatic nerve and the affected side were assessed. We also included reports lacking histological examination of sciatic nerve specimens but with a surgical diagnosis of pelvic endometriosis. Two authors abstracted data independently on standardized forms. The number of women and the side of the lesion were obtained from individual studies, and the combined frequency of left- and right-side sciatic nerve endometriosis in published reports was computed. TABULATION, INTEGRATION, AND RESULTS: Thirty-two reports including 63 subjects were selected. Endometriosis of the sciatic nerve was on the right side in 41 patients, on the left in 20, and bilateral in two. Considering only patients with unilateral sciatic nerve endometriosis, the observed proportion of right-side lesions (41 of 61 [67.2%]; 95% confidence interval 54.0%, 78.7%) significantly differed from the expected proportion of 50% (chi(2)(1) 7.23, P =.007). Among the 16 cases of histological demonstration of endometriosis infiltrating sciatic nerve roots or fibers, ten had it on the right side (62.5%) and six on the left. Twenty-six of the 38 subjects (68.4%) with surgical demonstration of pelvic endometriosis but without histopathologic evidence of direct sciatic nerve involvement were affected by right cyclic sciatica. CONCLUSION: The finding that two thirds of patients with sciatic nerve endometriosis had right-side lesions constitutes further evidence against the coelomic metaplasia theory. The interposition of the sigmoid colon between the regurgitated endometrial cells implanted on the left posterolateral pelvic peritoneum seems to protect the left lumbosacral plexus and sciatic nerve.

Adolescent↗
PubMed1998

Endometriosis and spontaneous abortion rate: a cohort study in infertile women.

OBJECTIVE: To ascertain if there is an association between endometriosis and spontaneous abortion. DESIGN: Prospective cohort study. SETTING: Medical School Hospital. POPULATION: 174 infertile women laparoscopically diagnosed with endometriosis and 174 infertile women in which endometriosis was ruled out by laparoscopy, in the same period of time. MAIN OUTCOME MEASURE: Spontaneous abortion. Non-progressive gestational sac and/or histological study. RESULTS: Per woman abortion rate was 7.47% (13/174) in the endometriosis group, similar to 5.74% (10/174) in the infertile women without endometriosis (RR=1.32: CI=0.53-3.36). Nor were there any differences in the per pregnancy abortion rate: 20.96% (13/62) in endometriosis vs. 16.94% (10/59) in non-endometriosis (RR=1.3; CI=0.47-3.57). The abortion rate was similar in the different AFS stages: 22.86% (8/35) in stage I, 16.67% (3/18) in II, 25% (1/4) in III and 20% (1/5) in IV. In stage I no differences were observed in patients who were managed expectantly or with medical treatment. CONCLUSION: Endometriosis is not associated with an increased abortion rate. The severity of disease expressed by AFS staging is not associated with an increase in the abortion rate. In stage I the treatment of endometriosis did not decrease abortion rates.

Abortion, Spontaneous↗
PubMed1993

Is endometriosis a disease?

Recent comparative studies and developments in our understanding of the pathogenesis and pathophysiology of endometriosis have led to increasing doubts about whether it should always be considered a disease. Widespread use of laparoscopy for gynaecological investigation and treatment, recognition of non-pigmented lesions which are more active than classical implants, and the documentation of microscopic lesions in visually normal peritoneum, have all resulted in an increase in the frequency with which endometriosis is diagnosed. Recent studies suggest a prevalence of up to 80% in women complaining of infertility or pelvic pain, but also in up to 22% of fertile asymptomatic women undergoing sterilization. Perhaps it is a normal physiological variant, being present in such a high proportion of the population. Circumstantial evidence suggests this may be so, and the results with placebo treatment in controlled trials suggest that endometriosis is self-limiting and will regress or disappear spontaneously in 58% of women. The frequency and severity of symptoms which are often presumed to result from endometriosis do not correlate with the extent or site of lesions. Most women are pain-free. There is no dysmenorrhoea in up to 77%, no dyspareunia in up to 70%, and no pelvic pain at all in up to 61% of women with endometriosis. The pathophysiology of pain related to endometriosis is not understood. There is no medical or conservative surgical treatment that is wholly effective for symptom relief, and there is considerable placebo benefit. All treatments have risks or side-effects, and recurrent symptoms will develop in up to 45% of women within 5 years. For these reasons treatment should only be used where endometriosis fulfils the criteria of a disease, showing signs of progression with tissue damage or physiological disturbance. Asymptomatic endometriosis without tissue damage should not be considered a disease and should not be treated. Treatment of pain associated with minor endometriosis, or prophylactic treatment to prevent progression, must be regarded as empirical and not the specific requirement to control what is a questionable disease.

Adolescent↗
PubMed2003

Diagnostic delay in women with pain and endometriosis.

BACKGROUND: Women with endometriosis claim that delayed diagnosis is a problem. Anglo-American studies have shown a delay from 3 to 11 years between the onset of pain symptoms and the final diagnosis of endometriosis. The aim of this study was to find the time difference between the onset of pelvic pain symptoms and the final diagnosis of endometriosis among Norwegian patients. MATERIAL AND METHODS: Questionnaires were sent to 400 women, of whom 313 were members of the Norwegian Endometriosis Association and 87 were patients with endometriosis being hospitalized at St Olav's Hospital, Trondheim, in recent years. The response rate was 89%. Among the 356 questionnaires returned, 95 were excluded as not fulfilling the inclusion criterion of surgically verified symptomatic endometriosis or incomplete questionnaires. Data were analyzed from 261 women, of whom 223 were members of the Norwegian Endometriosis Association. In all included patients, pain was an indication for diagnostic surgery. RESULTS: The mean delay in diagnosis was 6.7 +/- 6.2 years and the median delay was 5.0 years for the two groups in total. There was no statistically significant difference in delay between the two recruitment groups. Mean delay in diagnosis had not changed significantly with time. Women reporting infertility in addition to pain did not have a significantly shorter delay. CONCLUSION: In Norway there is a considerable delay in the diagnosis of endometriosis, with figures comparable to results from Anglo-American studies. A greater awareness of symptoms of endometriosis and a more rapid investigation should thus be encouraged.

Adult↗
PubMed2003

Record review of baboons with histologically confirmed endometriosis in a large established colony.

Spontaneous endometriosis was diagnosed in 43 baboons over a 14-year period. Thirty-seven have died; five remain alive; one was sold and lost to follow-up. The average age at diagnosis was 17.2 years; 29 (67%) were between 12 and 21 years of age. Fifteen (35%) were diagnosed by biopsy and received surgical excision of the endometriotic tissue; four of these were identified during caesarian section, confirming one prior report of endometriosis in pregnant animals. Twenty-eight (65%) were diagnosed at or shortly preceding necropsy. When diagnosed by a palpable abdominal mass, there was a significantly greater likelihood the animal died or was killed as a result of complications of endometriosis. When diagnosis was at necropsy, there was a significantly greater likelihood that the animal died from causes unrelated to endometriosis. Early identification with surgical removal appears to provide a benefit for both survival and delivering offspring after diagnosis. In twenty-one baboons (49%), endometriosis affected multiple sites within the peritoneal cavity. In the remaining baboons, lesions were more localized. Ovarian involvement was seen in sixteen (37%) of these baboons. This paper is the first to describe significant ovarian involvement in baboons, previously considered a limitation of the usefulness of this species as an animal model. We also describe the first reported endometriosis seeding of an abdominal surgery scar in a baboon. Many of these baboons were middle aged, had few or no offspring, or had evidence of a long duration of uninterrupted menstrual cycles, consistent with risk factors for women. Endometriosis was an incidental finding in 17 (40%) of these baboons, consistent with previous reports of minimal endometriosis as a common asymptomatic finding in baboons and in women. Overall, endometriosis in baboons presents a spontaneously occurring animal model that shares important features with the disease in women and the rhesus macaque.

Age of Onset↗
PubMed2002

Immunohistochemical staining with MIB1, bcl2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia.

AIMS: Preinvasive endocervical glandular lesions, termed cervical glandular intraepithelial neoplasia, are increasing in incidence. The distinction of cervical glandular intraepithelial neoplasia from benign mimics, especially tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia, can be difficult. This study investigates the value of immunohistochemical staining with MIB1, bcl2 and p16 in the distinction of cervical glandular intraepithelial neoplasia from these benign mimics. METHODS AND RESULTS: Immunohistochemical staining using the monoclonal antibodies MIB1, bcl2 and p16 was performed on cases of cervical glandular intraepithelial neoplasia (n = 21), tubo-endometrial metaplasia (n = 13), endometriosis (n = 7) and microglandular hyperplasia (n = 14). With tubo-endometrial metaplasia and microglandular hyperplasia staining with MIB1 was either negative or involved <10% of cells, while with cervical glandular intraepithelial neoplasia the majority of cases (86%) exhibited >10% positive cells. Two cases of endometriosis exhibited a MIB1 index of 10-30% while in the other cases <10% cells stained. With bcl2 the cells of microglandular hyperplasia were negative although there was staining of associated reserve cells in 43% of cases. All cases of tubo-endometrial metaplasia except one and all cases of endometriosis stained diffusely positive with bcl2. Cases of cervical glandular intraepithelial neoplasia were negative or exhibited focal staining. With p16 all cases of cervical glandular intraepithelial neoplasia exhibited diffuse strong positivity, generally involving 100% of cells, while all cases of microglandular hyperplasia were negative. Sixty-two percent of cases of tubo-endometrial metaplasia showed focal positivity, the remainder being negative. Cases of tubo-endometrial metaplasia were never diffusely positive with p16. In three cases of endometriosis there was staining of >50% of cells while the other cases were either focally positive or negative. CONCLUSIONS: A panel of antibodies, comprising MIB1, bcl2 and p16, is a useful adjunct to histology in distinguishing cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia. Cases of cervical glandular intraepithelial neoplasia are diffusely positive for p16 and generally exhibit a high proliferation index with MIB1, while bcl2 is negative or, at most, focally positive. Tubo-endometrial metaplasia and endometriosis are characterized by strong diffuse positivity with bcl2 and a low proliferation index with MIB1 (although occasional cases of endometriosis show moderate proliferative activity). p16 is negative or exhibits focal positivity in tubo-endometrial metaplasia but in endometriosis there may be quite widespread positivity. Microglandular hyperplasia shows a low proliferation index with MIB1 and is negative for bcl2 and p16.

Antibodies, Monoclonal↗
PubMed2000

Endometriosis and recurrent pregnancy loss.

A possible association between endometriosis and spontaneous abortion has been suggested in mostly uncontrolled and/or retrospective studies. Some controlled studies evaluating the association between endometriosis and spontaneous abortion showed important methodological shortcomings: heterogeneity between cases and controls, analysis of the abortion rate before the diagnosis of endometriosis, and selection bias of study and control groups. On the basis of controlled prospective studies, there is no evidence that endometriosis is associated with (recurrent) pregnancy loss or that medical or surgical treatment of endometriosis reduces the spontaneous abortion rate. In programs of assisted reproduction, some studies have shown that the number and quality of oocytes, the fertilization rate, and the implantation rate per embryo may be reduced in women with endometriosis, but this observation has not been confirmed by other investigators. Future studies evaluating the reproductive outcome of patients with endometriosis in assisted reproduction programs should include reliable information about the date and histological confirmation of the diagnosis of endometriosis, time interval between treatment with assisted reproduction and the last laparoscopy, possible recurrence of endometriosis, effectiveness of interim hormonal (suppressive) therapy, accuracy of ultrasound diagnosis, and accuracy of "negative" diagnosis.

Abortion, Habitual↗
PubMed1997

Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis.

To explore the role of nitric oxide (NO) and oxidative stress in the pathogenesis of adhesion formation and in endometriosis-associated infertility, we examined the peritoneal total antioxidant status (TAS) and the concentrations of products of NO metabolism in women with endometriosis (early stage, n = 12; advanced stage, n = 12) and in fertile women without endometriosis (n = 10). Peritoneal CA 125 and oestrogen and progesterone concentrations were also measured to examine their contributions to TAS and the production of NO. We failed to demonstrate any significant difference in TAS and in the products of NO metabolism in peritoneal fluids among women with early and advanced stages of endometriosis compared with fertile women without endometriosis during the early follicular phase. TAS and the concentration of the products of NO metabolism were not related to concentrations of CA 125, oestrogen or progesterone. The concentration of CA 125 in serum, but not in peritoneal fluid, was positively correlated with the severity of endometriosis. The volume of peritoneal fluid and the progesterone concentration were significantly increased in the group with advanced endometriosis. TAS and the concentration of the products of NO metabolism did not increase in peritoneal fluids from women with endometriosis during the early follicular phase. Their role in the pathophysiology of endometriosis needs to be explored further.

Antioxidants↗
PubMed2003

Inverse correlation between peritoneal fluid leptin concentrations and the extent of endometriosis.

BACKGROUND: The role of leptin in reproductive processes has received increasing attention. Because leptin has intrinsic angiogenic properties, may be induced by inflammatory cytokines and induces matrix metalloproteinases, we examined peritoneal fluid (PF) leptin concentrations in women with endometriosis. METHODS: PF samples were collected from 60 women undergoing laparoscopy for endometriosis, and 18 controls undergoing tubal sterilization. Fifty of the women with endometriosis had received no prior hormonal treatment, while 10 with moderate- severe endometriosis were using GnRH agonists. RESULTS: Women with untreated endometriosis had significantly higher (mean +/- SD) PF leptin levels (34.9 +/- 7.9 ng/ml) than controls (17.9 +/- 4.1 ng/ml; P < 0.001). However, PF leptin levels were inversely correlated with the stage of disease (r = -0.62; P < 0.001). Nevertheless, women with stage III-IV endometriosis maintained significantly higher PF leptin levels (26.3 +/- 4.8 ng/ml; P < 0.001) than controls. Although PF leptin levels were significantly higher in the secretory versus proliferative phase of the menstrual cycle, they remained higher in both phases in women with untreated endometriosis. PF leptin levels in women on GnRH agonists were similar to controls. CONCLUSIONS: PF leptin levels are elevated in women with endometriosis, but inversely correlated with extent of disease. These findings suggest a potential role for leptin in the pathogenesis of peritoneal endometriosis.

Adult↗
PubMed2004

Role of IL-18 in pathogenesis of endometriosis.

BACKGROUND: Endometriosis is a complex disease associated with a wide range of immune responses, including pain, adhesion, exudation of peritoneal fluid, elevation of cytokine levels and generation of autoantibodies. Interleukin (IL)-18 is a strong pleiotropic cytokine known to be involved in various immune diseases. The aim of this study is to elucidate the role of IL-18 in the pathogenesis of endometriosis. METHODS: IL-18 and IL-1beta concentrations were measured in the peritoneal fluid and sera of 39 endometriosis patients and 15 control women. Expression of IL-18 and IL-18 receptor alpha-chain (IL-18Ralpha) was analysed in endometriotic tissues immunohistochemically. The effects of IL-18 on cyclooxygenase (COX)-II gene expression were analysed in peritoneal fluid monocytes and endometriotic cells of endometriosis patients. RESULTS: IL-18 concentrations in the peritoneal fluid of endometriosis patients averaged 592.57 +/- 108.27 pg/ml, significantly higher than 260.50 +/- 55.88 pg/ml in non-endometriotic samples. IL-18 concentrations in the serum did not differ significantly between endometriosis and control patients. Similarly, no significant differences were observed in IL-1beta concentrations in either the peritoneal fluid or the serum. IL-18 and IL-18Ralpha were expressed in endometriotic tissues. IL-18Ralpha expression was also observed in cells infiltrating into the inflammatory area of the endometriosis patients. COX-II was induced in peritoneal fluid monocytes and in endometriotic cells in response to IL-18 stimulation. CONCLUSIONS: The elevation of IL-18 in the peritoneal fluid of endometriosis patients and the induction of COX-II in peritoneal monocytes by IL-18 suggest that IL-18 plays a pathogenic role in endometriosis.

Adult↗
PubMed2004

Increased frequency of migraine among women with endometriosis.

BACKGROUND: Our aim is to assess the prevalence and characteristics of headache in patients with endometriosis compared with women without this disease. METHODS: One hundred and thirty-three women with histologically proven endometriosis and 166 controls were interviewed by a neurologist experienced in headache diagnosis; the headache disorders were classified according to the 1988 International Headache Society criteria. RESULTS: The prevalence of migraine was significantly higher among women with endometriosis [n = 51, 38.3%; 95% confidence interval (CI) 30.1-47.2%] than in controls (n = 25, 15.1%; 95% CI 10.0-21.4%) (P < 0.001). Migraine with aura was observed in 18 women with endometriosis (13.5%) and in two controls (1.2%; P < 0.001). The age at migraine onset was significantly lower in women with endometriosis than in controls (16.4 versus 21.9 years; P = 0.001). No significant difference was observed in pain intensity and attack frequency between the two groups; a trend for women with endometriosis to have longer unmedicated attacks was observed. No significant correlation was observed between attack frequency, unmedicated headache duration, migraine intensity and the severity of endometriosis. CONCLUSION: Migraine is more frequent in women with endometriosis than in controls, although its presence and characteristics are not related to the severity of endometriosis.

Adult↗