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PubMed2006

Induction of endometriosis in the marmoset monkey (Callithrix jacchus).

Endometriosis is an estrogen-dependent gynaecological disease associated with pain and infertility, which occurs in humans and menstruating primates. In this study, the marmoset monkey (Callithrix jacchus), which is a non-menstruating primate with high circulating estrogen levels, was used to test firstly the hypothesis that endometriosis is based on uterine shedding into the peritoneal cavity, secondly to study the pathogenesis of endometriosis due to its estrogenic situation. Female marmoset monkeys (n = 29) were exposed to two different experimental procedures (non-invasive versus invasive) for intrapelvic placement of endometrial cells by uterine flushing over an experimental period of 2-3 years. First endometriotic foci were detected by colour Doppler ultrasound at the bladder, the uterus and the ovaries at the earliest after 4 months of either treatments. However, invasive induction was more effective in terms of the time-course of induction and the number of resulting endometriotic foci. The analysis of the endometriotic foci by histology, immunohistochemistry and molecular techniques allowed a division into two distinct groups: an initial developing stage occurred, which under further treatment led to the second stage of established endometriosis. Both procedures showed a treatment-dependent increase of vascular supply to the endometriotic foci over the experimental period. The invasive method induced the final established stage of endometriosis more rapidly, with the expression of steroid receptors, aromatase, 17betaHSD1 and CD10. Altogether, 72% of the treated marmoset monkeys developed endometriosis under our endometrial reflux protocols. Our data support the theory that endometriosis can be induced artificially in a non-menstruating primate (C. jacchus) by endometrial shedding into the peritoneal cavity. Because the marmoset is a primate with very high peripheral estrogen levels, this offers an interesting model for studying the pathogenesis of this estrogen-dependent disease, as well as for therapeutic impacts on enzymes involved in steroid metabolism.

17-Hydroxysteroid Dehydrogenases↗

PubMed1996

Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis.

Active endometriosis is characterized by hypervascularization both within and surrounding the implant; therefore the presence of angiogenic factors in the peritoneal environment would be of great importance. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. We sought to determine if VEGF was present in the peritoneal fluid of women with and without endometriosis, and to establish if differences exist between these groups. VEGF was present in all patients sampled. The fluid from patients with endometriosis contained significantly greater amounts of VEGF than controls. Cyclic variations in VEGF concentration were seen in fluid from patients with endometriosis, the VEGF concentration in proliferative phase being significantly higher than in the secretory phase. The concentration of VEGF in this fluid was also significantly higher than that found in the proliferative and secretory phases of women without endometriosis. No cyclic variations in VEGF were seen in the control group. We suggest that elevated levels of VEGF in the peritoneal fluid of patients with endometriosis may be critical in the pathogenesis of endometriosis.

Adult↗

PubMed1996

Insulin-like growth factor binding proteins in peritoneal fluid of women with minimal and mild endometriosis.

This prospective cohort study was carried out in a university-based infertility clinic to determine the profile of insulin-like growth factor binding proteins (IGFBPs) in patients with mild endometriosis and no obvious mechanical factor contributing to infertility. A total of 26 patients with minimal and mild endometriosis and 10 controls contributed peritoneal fluid at surgery. The variety, expression and levels of IGFBPs were determined by radio-immunoassay and Western ligand blots (WLBs) with quantitation by laser densitometer. A 27 kDa species was significantly lower and 31 kDa species tended to be lower in patients with endometriosis as determined by quantitative laser densitometer. The levels of IGFBP-3 detected by radioimmunoassay and by WLB were correlated in the control group and in the patients with endometriosis in the follicular phase but not in patients with endometriosis in the luteal phase. The level of 27 kDa species seen on WLBs did not appear to correspond to IGFBP-1 determined by radioimmunoassay and IGFBP-3 levels in luteal phase endometriosis patients also departed from values determined by radioimmunoassay. These discrepancies suggest a complex system to control levels of IGF in the peritoneum involving multiple binding proteins and proteases. The IGFBPs of patients with endometriosis may contribute to reproductive dysfunction and be able to serve as markers.

Adult↗

PubMed1995

The bubble test: a new tool to improve the diagnosis of endometriosis.

The objective of this study was to determine the clinical sensitivity and specificity of a bubbling phenomenon, including peritoneal surfaces, as a diagnostic test for endometriosis during laparoscopy. A prospectively controlled study of women with infertility of at least 1 year duration, who underwent laparoscopy, was conducted at a medical school-affiliated private infertility centre and research foundation. The study included 48 prospectively enrolled female infertility patients who underwent laparoscopy. Of these, 32 were found to suffer from endometriosis (group A) and 16 control patients did not show any evidence of disease (group B). The study involved the irrigation of the posterior cul-de-sac with short bursts of either saline or lactated Ringer's solution, utilizing a standard laparoscopic aspiration/irrigation system, and the subsequent observation for an excessive soap-like bubbling phenomenon (positive bubble test) in association with endometriosis. All 32 endometriosis patients (group A) demonstrated a positive bubble test. In contrast, only two of the 16 control patients (group B) were positive (P = 0.00242, Fisher's exact test; odds ratio, 8.000). A positive bubble test during laparoscopy was thus 100% sensitive and 88% specific for the diagnosis of endometriosis by laparoscopy, resulting in positive and negative predictive values of 94 and 100% respectively. Since the literature provides considerable evidence that the diagnosis of endometriosis during laparoscopy is frequently missed, a positive bubble test during laparoscopy therefore may be considered a reason to search further (possibly with biopsies) for endometriosis in the absence of obviously visible disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascitic Fluid↗

PubMed2002

Abnormal interleukin-1 receptor type II gene expression in the endometrium of women with endometriosis.

Interleukin 1 (IL-1) is a major proinflammatory cytokine that is believed to play a central role in the pathophysiology of endometriosis. The IL-1 receptor type II (IL-1RII) is known to bind to IL-1 and to inhibit its biological effects. In our previous studies, we showed that human endometrium expresses IL-1RII, and we observed reduced expression of the protein in women with endometriosis. The aim of this study was to investigate IL-1RII mRNA in the endometrial tissue of normal women (n = 26) and of patients with various degrees of endometriosis (n = 53). In situ hybridization showed that IL-1RII mRNA expression was significantly decreased in endometriosis, particularly during the early stages of the disease (stages I and II). This was quite obvious in both glandular and stromal cells, and it was corroborated by reverse transcription-polymerase chain reaction analysis of IL-1RII mRNA in the endometrial tissue of women with (n = 10) and without (n = 8) endometriosis. The reduced levels of IL-1RII mRNA in the endometrium of women suffering from endometriosis reveals a profound defect in IL-1RII gene expression and, consequently, a reduced capability of endometrial tissue to down-regulate IL-1 activity. Defective IL-1RII gene expression during the early stages of endometriosis (stages I and II) may contribute to the etiology of the disease.

Adult↗

PubMed2001

Anasarca and small bowel obstruction secondary to endometriosis.

Intestinal involvement by endometriotic tissue occurs in up to 37% of patients with endometriosis. The vast majority of patients do not experience symptoms related to the gastrointestinal tract. In particular, the complications of intestinal obstruction and malabsorption secondary to endometriosis are exceedingly uncommon. We present a 42-year-old woman with intestinal obstruction, protein-losing enteropathy, and anasarca secondary to endometriosis. She had a 1-year history of watery diarrhea, bloating, and abdominal pain with a 30-lb weight-loss over 3 months. She had no previous history of endometriosis, and laboratory investigations showed severe hypoalbuminemia, hypokalemia, and metabolic acidosis. Abdominal x-rays revealed air-fluid levels and dilated loops of small bowel. She underwent surgical resection with primary anastomosis. Pathologic evaluation showed extensive endometriosis of the small bowel and appendix, which resulted in complete obstruction. Segments of ileum also demonstrated moderate-to-marked blunting of the villi. Postoperatively, the patient had a slow recovery with resolution of anasarca and a gradual increase in her weight. This report illuminates the rare, yet significant, complications of intestinal endometriosis, including small bowel obstruction, the development of a protein-losing enteropathy, and anasarca. One should consider the possibility of intestinal endometriosis in the differential diagnosis of bowel obstruction in women of childbearing age.

Adult↗

PubMed1990

Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro.

Late proliferative phase endometrial stromal cells grown in short-term culture were used as a model for the stromal component of endometriotic implants. Cells were grown in medium alone and in medium supplemented by 5, 10, and 20% concentrations of the cell-free fractions of peritoneal fluid obtained from patients with and without endometriosis. Nine fluid-sample pairs were matched based on the presence or absence of endometriosis at laparoscopy and the similarity of peritoneal fluid estradiol concentrations. Stromal cell proliferation as reflected by 3H-thymidine incorporation during sequential cell harvests over 72 hours was greater for cells exposed to endometriosis peritoneal fluid than for those exposed to non-endometriosis peritoneal fluid. This reached statistical significance with exposure to peritoneal fluid concentrations of 10 and 20% (P less than .05). A linear dose-response relationship between 3H-thymidine incorporation and peritoneal fluid concentration could be derived only for stromal cells exposed to fluid samples obtained from endometriosis patients (r = 0.51; P less than .001). In addition, proliferation over 72 hours was significantly greater for cells grown in 20% endometriosis peritoneal fluid than for those grown in nutrient medium alone (P less than .001). These data imply that factor(s) secreted into the peritoneal fluid of endometriosis patients may play a role in the proliferation or maintenance of disease implants.

Adult↗

PubMed2005

Ten estrogen-related polymorphisms and endometriosis: a study of multiple gene-gene interactions.

OBJECTIVE: Genetic as well as hormonal factors are known to influence the development and clinical course of endometriosis. We aimed to investigate the association among 10 single nucleotide polymorphisms (SNPs) involved in the estrogen metabolism and endometriosis and to develop a multiple genetic model. METHODS: In a case-control study, we investigated the genotype frequencies of 10 estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls using sequencing-on-chip-technology with solid-phase polymerase chain reaction on oligonucleotide microarrays: catechol-O-methyltransferase, Val158Met G->A, 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17), vlV A->C, cytochrome P450 (CYP), 17 A2 allele T->C, CYP1A1 MspI RFLP T->C, CYP1A1 Ile462Val A->G, CYP19 Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor alpha IVS1 -401>C. Associations and 2-way interaction models between SNPs were calculated by stepwise logistic regression models. RESULTS: In a univariate model, HSD17 vlV A->C was associated with a significantly increased risk of endometriosis (P = .004; odds ratio 3.9, 95% confidence interval 1.6-9.8). When all 2-way interactions of investigated SNPs were ascertained, no significant interactions among SNPs were observed. In a multivariate model, HSD17 vlV A->C was also significantly associated with endometriosis (P = .002). CONCLUSION: We present data on multiple SNPs in patients with endometriosis indicating an association between HSD17 gene variation and the disease. Although not able to demonstrate interaction models of SNPs, we provide evidence of HSD17 vlV A->C as a low penetrance genetic marker of endometriosis. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2002

Laparoscopic diagnosis of endometriosis.

OBJECTIVE: To consider and explain the possibility of difficulties in diagnosis of endometriosis at previous laparoscopy DESIGN: Retrospective patient record review. SETTING: The Endometriosis Care Centre of Australia and the private practices of authors. SAMPLE: Two hundred and fifteen patients with clinical evidence of endometriosis examined laparoscopically between March 1999 and May 2001. MAIN OUTCOME MEASURES: Confirmation of endometriosis by histological biopsy. RESULTS: Endometriosis was confirmed in 168 of the 215 women. Of these women 38 had a previous negative laparoscopy within 12 months of the current laparoscopy. CONCLUSIONS: It is possible that in some of the patients, who previously had a negative laparoscopy, endometriosis was not recognised. Possible reasons for difficulty in diagnosis have been identified and techniques to improve diagnosis suggested. This retrospective study was performed to consider and explain the possibility of difficulties in diagnosis of endometriosis at previous laparoscopy.

Diagnosis, Differential↗

PubMed2004

Genetics of endometriosis: a role for the progesterone receptor gene polymorphism PROGINS?

OBJECTIVE: Endometriosis is a steroid-dependent disease with a particular genetic background, but the locations of possible genomic aberrations are still poorly clarified. We have investigated the potential association between endometriosis and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor (PR) gene, which has been reported previously to segregate with this disease. DESIGN: In a case-control study, we examined the PROGINS polymorphism of the progesterone receptor gene in 131 Italian women affected by endometriosis diagnosed according to published criteria for the definition of the definite disease. Control subjects were represented by 127 Italian women without laparoscopic evidence of the disease. MEASUREMENTS: Peripheral blood samples, DNA extraction and polymerase chain reaction (PCR) were used to genotype women for the presence of the PROGINS polymorphism. RESULTS: We found a statistically significant difference in the distribution of PROGINS genotypes between patients with and without endometriosis. The frequency of the PROGINS allele T2 was 17.2% and 11%, respectively, in affected women and in controls [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.0-2.8]. This association was stronger in patients with more severe forms of endometriosis, such as an infiltrating disease or a disease characterized by severe pelvic adhesions (OR 2.4, 95% CI 1.2-4.8; and OR 2.7, 95% CI 1.4-5.3, respectively). Combination of the results from an earlier study and the current data indicates that carrying the allele variant T2 is associated with a twofold increase in the risk of developing endometriosis (OR 2.0, 95% CI 1.3-2.9). CONCLUSIONS: Our results further support the idea that the PROGINS polymorphism of the progesterone receptor may be associated with an increased risk of endometriosis.

Adult↗

PubMed2004

Women's experience of endometriosis.

BACKGROUND: Endometriosis is a chronic disease affecting between 5% and 15% of women of reproductive age. Diagnosis can be delayed for many years, despite the existence of severe pain, and women often find that their experiences are not taken seriously by health professionals. Little research has been conducted into how endometriosis affects their lives. AIM: The aim of this paper is to report a study exploring women's experience of living with endometriosis. METHOD: A qualitative approach was used, in which women were asked to relate their stories starting from the first experience of symptoms that they associated with endometriosis. Key areas to be followed-up during interviews were identified by women with endometriosis who were not participants. Fifteen semi-focused interviews were conducted, and thematic and content analysis were carried out using the identified key areas, and themes elicited from initial analysis of the interview transcripts. From these two processes the final themes of delay in diagnosis, pain, dyspareunia, treatment, work and social relationships, the workplace, and the future emerged. FINDINGS: Despite the existence of severe pain, often described as 'intense' or 'overwhelming', women experienced delay in receiving a diagnosis of endometriosis, and their symptoms were frequently trivialized or normalized. This, and the limited effectiveness of treatments, affected relationships with partners and family, work, and sexual relations, although individual experiences in each area were diverse. CONCLUSION: The experience of endometriosis pervades all aspects of a woman's life. This experience is compounded by the side effects of many treatments. Women with this disease need to be taken seriously, and not have their pain trivialized or normalized. Nurses are often well-placed to assist patients in receiving sensitive and appropriate care.

Adaptation, Psychological↗

PubMed1993

Endometriosis and luteal phase defect.

It has been reported that there exists a correlation between endometriosis and the luteal phase defect (LPD) as one of the determinants in infertility. In some theories, the hampered maturation of the corpus luteum is believed to be caused by the reduction of LH receptors, increase in prolactin, prostaglandin and macrophages in endometriosis. The purpose of this clinical study is to prove the hypothesis that there exists a significant correlation between endometriosis and the luteal phase defects in infertility. The samples were taken at random from 150 women with infertile marriages on whom ovulation was assumed to have occurred, from January 1981 to December 1985. The assumption that there might have occurred ovulation is determined through the observation of their basal body temperature (BBT) chart. Endometrium biopsies to diagnose the LPD were taken at the end of their luteal phase. A laparoscopy examination to diagnose the pelvic endometriosis was done in the following cycle. Of 84 patients with endometriosis, 44 (55.4%) had luteal phase defects, while the remaining 40 (47.6%) patients had no luteal phase defects. Of the 66 patients without endometriosis, 27 (40.9%) had luteal phase defects, while the remaining 39 (59.1%) did not have luteal phase defects. These differences were not significant (p > 0.05). In summary, this clinical study fails to show the existence of significant correlation between endometriosis and the luteal phase defect.

Adult↗

PubMed1997

Intrinsic ureteric involvement by endometriosis: a case report.

Endometriosis occasionally involves the urinary tract, and a ureteral obstruction from this order constitutes a rare variant with serious consequences. Intrinsic ureteric involvement by endometriosis is an exceedingly rare event. This case report describes intrinsic ureteric involvement by endometriosis. The case involved 47-year-old woman, gravida 4, para 2, who had a 4-year history of dysmenorrhea and hypermenorrhea. An intravenous pyelogram showed a right hydronephrosis. She underwent a total abdominal hysterectomy and a right ureteroureterostomy. A pathologic examination revealed complete obstruction of the right ureter by intrinsic intramural endometriosis. We conclude that because ureteral endometriosis, especially intrinsic endometriosis, is usually silent and results in a high rate of renal loss before recognition, physicians should have a hightened awareness of this uncommon but serious manifestation of endometriosis.

Endometriosis↗

PubMed1978

A study of plasma progesterone, oestradiol-17beta, prolactin and LH levels, and of the luteal phase appearance of the ovaries in patients with endometriosis and infertility.

Thirty-four infertile patients with regular cycles and endometriosis were studied and compared to a control group of 28 women. The endometriosis was classified as mild (n = 16), moderate (n = 9) and severe (n = 9) according to Acosta et al (1973). The interval between the LH peak and the onset of subsequent menstruation was shorter (P = 0.024) in patients with endometriosis than in the control group. In mild endometriosis, oestradiol-17beta levels fell on the day after the LH peak, but this was not the case in moderate and severe endometriosis. In mild, moderate and severe endometriosis the plasma progesterone concentration did not rise on the first day following the LH peak, and at laparoscopy significantly (P less than 0.005) less ovulation stigmata were present. We conclude that endometriosis is associated with luteinization in situ and that this may explain the associated infertility.

Endometriosis↗

PubMed2001

Does deep endometriosis infiltrating the uterosacral ligaments present an asymmetric lateral distribution?

OBJECTIVE: To investigate whether deeply infiltrating endometriosis occurs with equal frequency between left and right uterosacral ligaments. DESIGN: Retrospective analysis of consecutive cases. SETTING: Department of gynaecological surgery in a tertiary care university hospital in Paris, France. POPULATION: One hundred and thirty consecutive women with laparoscopic resection of histologically proven deep endometriosis infiltrating the uterosacral ligaments. METHODS: Laterality, intraoperative aspect of the uterosacral ligaments, and associated endometriosis were recorded during laparoscopy. Deep endometriosis infiltrating the uterosacral ligaments was considered as histologically proven in the presence of endometrial glands and stroma. MAIN OUTCOME MEASURE: Frequency of left- and right-sided deep endometriosis infiltrating the uterosacral ligaments. RESULTS: The left uterosacral ligament alone was involved in 69 cases; the right uterosacral ligament alone was involved in 38 cases; both were involved in 23 cases. For patients with unilateral deep endometriosis infiltrating the uterosacral ligaments the observed proportion of endometriosis involving the left uterosacral ligament (69/107, 64.5%) was significantly different from the expected proportion of 50% (chi2 = 8.98; P < 0.01). CONCLUSION: Anatomical differences between left and right hemipelvis and differences in the frequency of ovulation between right and left ovary could explain these results.

Adult↗

PubMed1993

Mitogen induced production of polyclonal IgG is decreased in women with severe endometriosis.

PROBLEM: The etiology and/or pathogenesis of endometriosis may involve aspects of both humoral and cellular immunity. METHOD: In this investigation, we analyzed the ability of B lymphocytes from distinct patient groups for production of IgG1, IgG2, and IgG3 following in vitro stimulation with polyclonal B-cell mitogens (pokeweed mitogen and Staphylococcus aureus Cowan strain I) after in vitro stimulation with polyclonal B-cell activators. RESULTS: We observed that the in vitro production of IgG1, IgG2, and IgG3 was identical among fertile controls (no endometriosis; N = 22), infertile women without endometriosis (N = 22), infertile women without endometriosis (N = 20) and patients with stage 1 or 2 endometriosis (N = 31). In contrast, in vitro IgG2 production was significantly reduced among women with stage 3 or 4 endometriosis (N = 11) compared to controls (P < 0.001). CONCLUSION: Since the number of circulating B cells was similar in each patient group studied, the reduced production of IgG2 in patients with stage 3 or 4 disease was not merely due to fewer antibody producing cells in those subjects, and we speculate that the observed decrease in polyclonal IgG2 production among these patients is due to a primary defect. In additional studies, we observed that polyclonal IgG2 production was normal among stage 3 or 4 patients treated with danazol (N = 11), but significantly reduced in patients treated with gonadotropin releasing hormone agonists (N = 8). Although not conclusive, these data suggest that danazol may have the capacity to correct the defective production of polyclonal IgG2 in patients with severe endometriosis.

Antibody Formation↗

PubMed1994

Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) in peritoneal fluid and macrophage-conditioned media of women with endometriosis.

PROBLEM: The presence of the various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to activation of peritoneal macrophages, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interferon gamma (IFN-gamma) and interleukin-6 (IL-6), and peritoneal macrophage production of IL-6, in women with and without endometriosis. METHOD: Peritoneal fluid was obtained from 62 women at the time of diagnostic or operative laparoscopic surgery for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IFN-gamma and IL-6 levels in peritoneal fluid samples and macrophage conditioned media were determined by commercial ELISA. RESULTS: IL-6 was significantly higher in the macrophage conditioned media of women with endometriosis as compared with controls. IL-6 levels were fourfold higher in early stage endometriosis (P < 0.05) and eightfold higher in advanced endometriosis. There were no significant differences between groups in the peritoneal fluid levels of IL-6 or IFN-gamma. CONCLUSIONS: Peritoneal macrophage IL-6 secretion is increased in women with endometriosis, and appears to correlate with disease stage. IFN-gamma does not appear to be responsible for the activation of macrophages in women with endometriosis.

Adult↗

PubMed1996

Antibodies to endometrial transferrin and alpha 2-Heremans Schmidt (HS) glycoprotein in patients with endometriosis.

PROBLEM: Identifying the endometrial antigens inciting autoimmunity is important in setting up an antibody assay for a non-invasive diagnosis and clinical monitoring of endometriosis. METHODS: Two-dimensional gel electrophoresis of endometrial extracts, Western blot analysis, passive hemagglutination and enzyme-linked immunosorbent assay (ELISA), amino acid sequencing and molecular studies were done on chosen antigens. Forty-six women with endometriosis, 4 women with uterine leiomyomata, 4 with pelvic adhesions, 3 with repeat Cesarean sections (conditions that coexist with or predispose to endometriosis) and 46 controls participated. RESULTS: Antigens with molecular weights (MW) of 64 kDa [isoelectric point (pI) of 3.5-4.0] and 72 kDa (pI of 4.5) bound to IgG in all patients with endometriosis, but not the controls. Amino acid sequencing of the proteins revealed that they had homology to alpha 2-Heremans Schmidt (HS) glycoprotein (MW: 64 kDa) and transferrin (MW: 72 kDa). Endometriosis patients had significant antibody levels to these two proteins (predictive value of 80-90%). The analysis of patients' endometrial RNA detected the message for alpha 2-HS glycoprotein and transferrin. Albumin (pI 5.5) and collagen (pI 3.5) failed to elicit antibody responses. CONCLUSIONS: Patients with endometriosis have significant antibodies to endometrial transferrin and alpha 2-HS-glycoprotein. We can effectively use an antibody assay using these antigens for diagnosing endometriosis.

Adult↗