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PubMed2005

[Expressions of aromatase P450 and estrogen receptor in eutopic and ectopic endometrium in endometriosis and their correlation with endometriosis].

OBJECTIVE: To detect the expression of aromatase P450 and estrogen receptor (ER) in eutopic and ectopic endometrium in endometriosis and their correlation with endometriosis. METHODS: Forty patients who had undergone operation because of endometriosis (all were stage III-IV according to the revised American Fertility Society classification) were enrolled and 83 tissue specimens from different locations of disease foci were obtained and divided into five groups according to the location: group I, eutopic endometrium of 25 cases; Group II, ovarian endometriosis tissues of 23 cases; Group III, vagina-rectum endometriosis tissues of 11 cases; Group IV, peritoneum endometriosis tissues of eight cases; and group V, uterine serosa endometriosis tissues of 16 cases. Control group consisted of normal endometrium taken from 20 fertile women who had endometrial curettage before placement of intrauterine device. The routine two-step immunohistochemical technique was used to measure the expression of aromatase P450 and ER in endometrial cells. RESULTS: Expressions of aromatase P450 and ER in group I [histochemistry score (H-score), 2.6 +/- 1.0, 3.8 +/- 0.5] were significantly higher than those in control group (both P < 0.01), group II (1.4 +/- 1.0, 1.9 +/- 1.6) (P < 0.05, P < 0.01), and group III (1.2 +/- 0.9, 1.8 +/- 1.6) (both P < 0.05). Expressions of aromatase P450 and ER had positive correlation in all groups (r = 0.577, P < 0.01). CONCLUSIONS: Aromatase P450 could increase estrogen and estrogen receptor levels in the local ectopic tissues, thus promoting the growth and implantation of endometriosis. Different types of endometriosis focus have different levels of hormone regulation.

Adult↗
PubMed1997

Treatment of bowel endometriosis: a report of six cases of colorectal endometriosis and a survey of the literature.

From October 1989 to September 1994, we performed six intestinal resections for rectal and sigmoidal endometriosis. The average age of the patients was 32 years old, and most had symptoms. In all cases coloscopy showed a normal mucosa. Patients had successfully been treated with hormones previously, but had relapsed when the treatment was stopped. Bowel resection was segmental, with immediate end to end anastomosis in five patients, and partial in one patient. Genital endometriosis was diagnosed in three cases and was then treated during the same procedure. A low colorectal anastomosis was complicated by a fistula, but no recurrence was observed after surgical treatment. Intestinal endometriosis tract is in 70% of cases located on the rectosigmoid. An association with genital endometriosis tract is observed in 80% of the cases. Deep rectosigmoidal endometriosis with symptoms is resistant to hormonal therapy and necessitates a surgical treatment by intestinal resection. The pelvis has always to be explored, with full evaluation and surgical treatment of genital endometriosis when necessary. Appendicular endometriosis should be removed surgically. Postoperative treatment can be additionally prescribed in cases of genital endometriosis and for leftover digestive location.

Adult↗
PubMed2005

Endometriosis-specific genes identified by real-time reverse transcription-polymerase chain reaction expression profiling of endometriosis versus autologous uterine endometrium.

CONTEXT: The etiology and molecular pathogenesis of endometriosis, a prevalent estrogen-dependent gynecologic disease, are poorly understood. OBJECTIVE: The objective of the study was to identify the differentially expressed genes between autologous ectopic and eutopic endometrium. DESIGN: Subtractive hybridization was used for a genome-wide search for differentially expressed genes between autologous ectopic and eutopic endometrium. Real-time RT-PCR was used for gene expression profiling in the paired tissue samples taken from multiple subjects. PATIENTS: The paired pelvic endometriosis and uterine endometrium tissue biopsies were procured from 15 patients undergoing laparoscopy or hysterectomy for endometriosis. RESULTS: Seventy-eight candidate genes were identified from the subtractive cDNA libraries. Seventy-six of these genes were investigated in approximately 8000 real-time PCR for their differential expression in 30 paired tissue biopsies from 15 patients affected by endometriosis. Cluster analysis on gene expression revealed highly consistent profiles in two groups of genes, despite the clinical heterogeneity of the 15 cases. Thirty-four genes specific to early disease point to their potential roles in establishment and evolution of endometriosis. Most interestingly, 14 genes were consistently dysregulated in the paired samples from the majority of the patients. Of these, there were two uncharacterized transcripts and two novel genes, and 10 were matched to known genes: IGFBP5, PIM2, RPL41, PSAP, FBLN1, SIPL, DLX5, HSD11B2, SET, and RHOE. CONCLUSIONS: Dysregulation of 14 genes was found to be overtly associated with endometriosis. Some of these genes, known to participate in estrogen activities and antiapoptosis, may play a role in the pathogenesis of endometriosis and may represent potential diagnostic markers or therapeutic targets for endometriosis.

Adult↗
PubMed1999

Oral contraceptive use and risk of endometriosis. Italian Endometriosis Study Group.

OBJECTIVE: To analyse the association between use of oral contraception and risk of pelvic endometriosis. DESIGN: We compared use of oral contraception in women with and without endometriosis. PARTICIPANTS: Eligible for the study were women with primary or secondary infertility (n = 393) or chronic pelvic pain (n = 424), requiring laparoscopy, consecutively observed between September 1995 and January 1996 in 15 obstetrics and gynaecology departments in Italy. RESULTS: Out of the 817 women included in the study, 345 had a diagnosis of endometriosis; 164 (47.5%) women with endometriosis and 139 (29.4%) without the disease reported ever using oral contraception. In comparison with never users the estimated odds ratios (OR) of endometriosis were 1.8 (95% CI 1.0-3.3) in current users and 1.6 (95% CI 1.1-2.4) in ex-users. No clear relation emerged between duration of oral contraceptive use and risk of endometriosis. In comparison with never users, the OR was 1.8 (95% CI 1.1-3.0) for women reporting their last use of oral contraception < 5 years before interview and 1.5 (95% CI 0.9-2.5) for those reporting their last use > or = 5 years before interview. CONCLUSIONS: The study suggests that oral contraception is associated with an increased risk of endometriosis but this finding is based on a selected population and cannot generalised to all women with endometriosis.

Adult↗
PubMed2005

Peritoneal fluid cytokines and sICAM-1 in minimal endometriosis: search for discriminating factors between infertility and/or endometriosis.

OBJECTIVE: To evaluate cytokine levels (IL-1beta, TNF-alpha, IL-6, IL-8), soluble intercellular adhesion molecule-1 (sICAM-1) and number of macrophages in peritoneal fluid (PF) of women with no minimal endometriosis and associated (or not) infertility in order to discriminate between infertility and/or endometriosis. STUDY DESIGN: Cytokines and sICAM-1 were measured by using quantitative enzyme-linked immunosorbent assay (ELISA) while the macrophages were identified by May-Grunwald-Giemsa and non-specific esterase staining and presented as medians. The measurements were performed in 78 women belonging to four selected subgroups according to their endometriosis and/or infertility status. Statistical analysis was performed using Kruskal-Wallis non-parametric ANOVA test. Additionally, discriminant function analyses were performed. RESULTS: We have found the most elevated macrophage numbers in the groups of women with endometriosis. IL-1beta did not present any statistically significant values differentiating the analysed subgroups. IL-6 (110.0 pg/ml) and TNF-alpha exhibited the highest concentrations (statistically significant) in a group of fertile women with endometriosis. IL-8 clearly differentiated between the subgroups with infertility and sICAM-1 was statistically significantly elevated in the subgroups of infertile women. In the forward discriminant analysis, when subdividing the studied population according to its infertility status (we considered macrophages, IL-8 and IL-6 in order of probability values), we have found striking probability value of 92% for the correct classification into an infertile population. CONCLUSION: Out of the range of the analysed factors we have found only the sICAM-1 to be singled out between the standard discriminant analysis and the forward one. However, this important flagging molecule might be of considerable value for discrimination between different types of pathology at the level of immune effector function. The increased levels of TNF-alpha and IL-6 signified a group of fertile women with endometriosis; however only IL-6 presented a discriminating value in multifunctional analysis of examined subgroups. The analysed range of factors had a greater tendency to discriminate between infertility status rather than endometriosis.

Adult↗
PubMed2004

Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis: possible association with progression of endometriosis.

Allograft inflammatory factor-1 (AIF-1) is a cytokine originally identified in rat cardiac allografts with chronic rejection. AIF-1 is expressed in various human immune-related tissues and is thought to play a role in inflammatory responses and the immune activation and function of macrophages. Expression has also been shown in human placentas and bovine embryos, suggesting that AIF-1 may be involved in reproductive function. Immune factors are thought to be involved in the pathogenesis of endometriosis. High concentrations of activated macrophages and various cytokines have been found in the peritoneal fluid of patients with endometriosis. In the current work we examined the expression of AIF-1 in human eutopic endometrium and endometriosis, and measured AIF-1 in peritoneal fluid samples from women with and without endometriosis. RT-PCR, Western blot analysis, and immunohistochemistry showed that AIF-1 mRNA and protein were expressed both in eutopic endometrium and in endometriotic tissue. In eutopic endometrium, expression was greater in the late secretory and menstrual phases than in other phases of the menstrual cycle (P < 0.01). AIF-1 protein was present in greater amounts in peritoneal fluid from patients with endometriosis than in women without it (P < 0.01), and its concentration correlated with the Revised American Society for Reproductive Medicine score (rs = 0.693; P < 0.0001). Peritoneal macrophages from endometriosis patients secreted more AIF-1 than those from unaffected women (P < 0.05). AIF-1 release from macrophages was stimulated by IL-1beta (P < 0.01) and interferon-gamma (P < 0.05). These results demonstrate for the first time that AIF-1 is expressed in eutopic endometrium and endometriotic tissue, suggesting that AIF-1 is one cytokine in the local network involved in the onset of menstruation. AIF-1 derived from peritoneal macrophages may also possibly play a significant role in the pathophysiology and progression of endometriosis.

Adult↗
PubMed1993

[Effect of endometriosis pill No. 2 on beta-endorphin and dynorphin in endometriosis].

In order to explore the correlation between endometriosis and beta-Endorphin, Dynorphin, the beta-Endorphin and Dynorphin levels in menstrual blood of normal women and patients with endometriosis, and the pituitary-hypothalamic beta-Endorphin and Dynorphin levels in animal models were determined. The results indicated: (1) The plasma beta-Endorphin and Dynorphin levels in patients with endometriosis were significantly lower than those in normal women (P < 0.05); the plasma beta-Endorphin levels in patients with endometriosis were significantly higher after treatment of Endometriosis Pill No. 2 (P < 0.05). (2) The pituitary and hypothalamic beta-Endorphin levels in untreated group were significantly higher than those in the control group (P < 0.05); the hypothalamic beta-Endorphin in treated group were obviously higher than those in untreated group (108.35 +/- 35.38 and 66.63 +/- 14.29 respectively). The above-mentioned results presented evidence that the low beta-Endorphin and Dynorphin levels in endometriotic patients play a role in dysmenorrhea; the effect of Endometriosis Pill No. 2 in relieving dysmenorrhea was realized through an increase of plasma and hypothalamic beta-Endorphin levels. (3) The Pituitary and hypothalamic beta-Endorphin levels were significantly different between the animal models of endometriosis and normal control groups.

Adult↗
PubMed2005

Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis.

OBJECTIVE: To investigate the role of interleukin (IL)-16 in peritoneal fluid in the pathogenesis of endometriosis. DESIGN: Comparative and laboratory study. SETTING: University of Tokyo Hospital. PATIENT(S): Peritoneal fluids (PFs) were collected from women without endometriosis (n = 34) and with endometriosis (stages I/II, n = 30; stages III/IV, n = 58). Peritoneal fluid mononuclear cells (PFMCs) were collected from six women. INTERVENTION(S): The PFs were collected; PFMCs were isolated and cultured with or without recombinant human (rh) IL-16. MAIN OUTCOME MEASURE(S): Concentrations of IL-16 in PFs were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of IL-6, tumor necrosis factor-alpha (TNF-alpha), and IL-1beta in culture media of PFMCs were determined by ELISA. RESULT(S): The IL-16 concentrations in the PF of women with advanced endometriosis (stages III/IV) (330 pg/mL, 231-501; median, interquartile range) were significantly higher (P=.0016) than those without endometriosis (229 pg/mL, 174-311). The PFMCs cultured with rhIL-16 released an increased amount of IL-6, TNF-alpha and IL-1beta, which was a 1.17-, 1.33-, and 1.54-fold increase, respectively, over that in the control culture. CONCLUSION(S): The present study indicates that IL-16 in PF may play a role in the pathogenesis of endometriosis by initiating or sustaining inflammatory responses in the peritoneal cavity.

Adult↗
PubMed1982

Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women.

To test the widely accepted--but not well-supported--impression that endometriosis and infertility are associated, we compared the prevalence of endometriosis visualized at laparoscopy in 100 patients being evaluated for infertility and in 200 fertile control subjects (two age-matched to each patient) undergoing tubal ligation. The extent of endometriosis and adhesions noted in the operative reports was classified according to the system proposed by The American Fertility Society. Endometriosis was found in 21 of the 100 infertile patients--mild in 11, moderate in 8, severe in 2. It was found in 4 (2%) of the 200 controls and was mild in all 4. Thus, endometriosis is more often present, and more often severe, among infertile patients. The risk of infertility was estimated to be almost 20 times greater with endometriosis than without. These data support the clinical impression that an association exists.

Adult↗
PubMed1995

The revised American Fertility Society classification of endometriosis: reproducibility of scoring. ZOLADEX Endometriosis Study Group.

OBJECTIVE: To assess the reproducibility in staging endometriosis using the revised American Fertility Society (AFS) classification of endometriosis. DESIGN: Visual documentation of laparoscopies of 315 women with endometriosis was scored by the investigators and a blinded reviewer. SETTING: Patients from private practice institutional setting. PARTICIPANTS: Patients who participated in a multicenter trial to study the efficacy and safety of a GnRH agonist (GnRH-a). INTERVENTIONS: Laparascopic visual documentation of the extent of endometriosis before and after 6 months of GnRH-a therapy. MAIN OUTCOME MEASURE: The reproducibility of the AFS classification system comparing scoring during laparoscopy and by a blinded reviewer. RESULTS: Good to fair agreement scoring endometriosis between the investigator and the blinded reviewer was noted. CONCLUSIONS: Visual documentation may be used to determine the stage of endometriosis using the revised AFS classification guidelines.

Endometriosis↗
PubMed1998

Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. The Canadian Collaborative Group on Endometriosis.

OBJECTIVE: To assess whether infertile women with minimal or mild endometriosis have lower fecundity than women with unexplained infertility. DESIGN: Prospective cohort study. SETTING: Twenty-three infertility clinics across Canada. PATIENT(S): Three hundred thirty-one infertile women aged 20-39 years. INTERVENTION(S): Diagnostic laparoscopy for infertility. Infertile women with minimal or mild endometriosis (n = 168) were compared with women with unexplained infertility (n = 263). Both groups were managed expectantly. The women were followed up for 36 weeks after the laparoscopy or, for those who became pregnant, for up to 20 weeks of the pregnancy. MAIN OUTCOME MEASURE(S): Fecundity refers to the probability of becoming pregnant in the first 36 weeks after laparoscopy and carrying the pregnancy for > or = 20 weeks. The fecundity rate is the number of pregnancies per 100 person-months. RESULT(S): Fecundity was 18.2% in infertile women with minimal or mild endometriosis and 23.7% in women without endometriosis (log-rank test). The fecundity rate was 2.52 per 100 person-months in women with endometriosis and 3.48 per 100 person-months in women with unexplained infertility. The crude and adjusted fecundity rate ratios were 0.72 and 0.83 (95% confidence interval = 0.53-1.32), respectively. CONCLUSION(S): The fecundity of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility.

Adult↗
PubMed2001

Development of an endometriosis quality-of-life instrument: The Endometriosis Health Profile-30.

OBJECTIVE: To describe a new disease-specific questionnaire with established measurement properties that addresses the dimensions of health-related quality of life considered important to women with endometriosis. METHODS: The Endometriosis Health Profile-30 was developed in three stages. Stage 1 included open-ended exploratory interviews with 25 women to generate the items on the questionnaire. Stage 2 was an 87-item questionnaire administered in a postal survey to identify the most salient dimensions of health-related quality of life. In stage 3, the reliability and validity of the questionnaire were evaluated. RESULTS: The final instrument contained a core questionnaire with 30 items and five scales: pain, control and powerlessness, emotional well-being, social support, and self-image. Six modular parts consisting of 23 questions were also developed and measured the areas of sexual intercourse, work, relationship with children, feelings about the medical profession, treatment, and infertility. All the scales achieved high internal reliability, with Cronbach's alpha coefficient ranging from 0.83 to 0.93 (core questionnaire) and 0.79 to 0.96 (modules). The intraclass correlation coefficients to evaluate the test-retest reliability were high (range 0.88-0.98, P <.001). Content validity was demonstrated as the questionnaire was developed from interviews of patients rather than existing literature and clinical scales. Construct validity was assessed by correlating the Endometriosis Health Profile-30 scales with the relevant Short Form-36 scales. High correlations for all comparisons were found (-0.41 to -0.73). CONCLUSION: The Endometriosis Health Profile-30 is a reliable, valid, patient-generated instrument to measure the health-related quality of life of women with endometriosis. Its application in various health care settings will provide new and valuable information on the effect of endometriosis on health-related quality of life from the patients' perspective.

Adolescent↗
PubMed1999

Risk factors for pelvic endometriosis in women with pelvic pain or infertility. Gruppo Italiano per lo Studio dell' endometriosi.

OBJECTIVE: The objective of the study was to analyse the relationship between selected characteristics and risk of pelvic endometriosis. STUDY DESIGN: Eligible for the study were 817 women with primary or secondary infertility or pelvic pain requiring laparoscopy. Of these, 393 were included for infertility and 424 for pelvic pain. RESULTS: A total of 345 (42.2%) had a diagnosis of endometriosis and 472 did not have the disease. Multiparous women had endometriosis less frequently than nulliparous, the estimated odds ratios (OR) were respectively 0.9 (95% confidence interval, CI, 0.5-1.6) and 0.4 (95% CI 0.2-0.7) in women reporting one and two or more births. In comparison with women reporting no spontaneous abortion, the estimated OR was 0.3 (95% CI 0.2-0.5) in those who reported > or =1 miscarriage. In comparison with women reporting menstrual cycles lasting > or =25 days subjects with totally irregular menstrual cycles had a reduced risk of endometriosis (OR 0.6, 95% CI 0.3-0.9). No significant association emerged between smoking, age at menarche and risk of endometriosis. CONCLUSIONS: this study confirms, with a different methodological approach to previously published studies, that multiparity, a history of abortion and lifelong irregular menstrual pattern decrease the risk of endometriosis in women with pelvic pain and infertility.

Adult↗
PubMed1997

Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.

BACKGROUND: Minimal or mild endometriosis is frequently diagnosed in infertile women. It is often treated by resection or ablation of the lesions, but whether this improves fertility has not been established. We carried out a randomized, controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis. METHODS: We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis. During diagnostic laparoscopy the women were randomly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only. They were followed for 36 weeks after the laparoscopy or, for those who became pregnant during that interval, for up to 20 weeks of pregnancy. RESULTS: Among the 172 women who had resection or ablation of endometriosis, 50 became pregnant and had pregnancies that continued for 20 weeks or longer, as compared with 29 of the 169 women in the diagnostic-laparoscopy group (cumulative probabilities, 30.7 percent and 17.7 percent, respectively; P=0.006 by the log-rank test). The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months (rate ratio, 1.9; 95 percent confidence interval, 1.2 to 3.1). Fetal losses occurred in 20.6 percent of all the recognized pregnancies in the laparoscopic-surgery group and in 21.6 percent of all those in the diagnostic-laparoscopy group (P=0.91). Four minor operative complications (intestinal contusion, slight tear of the tubal serosa, difficult pneumoperitoneum, and vascular trauma) were reported (three in the surgery group and one in the control group). CONCLUSIONS: Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women.

Adult↗
PubMed1998

Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis.

Danazol is routinely administered orally to inhibit ovulation and to treat pelvic endometriosis. However, recent evidence suggests that danazol can act directly on endometriotic tissue in vitro to inhibit DNA synthesis and induce apoptosis. Danazol was administered via the vagina in this study, using a vaginal ring drug delivery system containing 1500 mg of danazol. This therapy was effective for treatment of pelvic endometriosis, especially for deeply infiltrating endometriosis, resulting in a cure of dysmenorrhoea and tenderness in the cul-de-sac within 3 months, and of induration or nodularity in the cul-de-sac within 7 months. Moreover, conception was possible during insertion of the vaginal ring in 17 out of 31 infertile women with deeply infiltrating endometriosis, and in two out of eight infertile women with ovarian endometriotic cysts not adhering to the cul-de-sac and without deeply infiltrating endometriosis. Serum danazol concentrations, high during oral daily 400 mg danazol therapy, but undetectable during vaginal danazol ring therapy, explain why ovulation and conception could occur during insertion of the vaginal danazol ring, and why general side-effects, which are often observed during oral danazol therapy, were not observed during vaginal danazol ring therapy. Danazol seems to be absorbed through the vaginal mucosa and reaches the deeply infiltrating endometriosis via diffusion.

Absorption↗
PubMed1998

Characteristics related to the prevalence of minimal or mild endometriosis in infertile women. Canadian Collaborative Group on Endometriosis.

The objective of this case-control study is to identify factors associated with the prevalence of minimal or mild endometriosis among infertile women. Cases (N = 329) were women diagnosed by laparoscopy with minimal or mild endometriosis and without any other factors explaining their infertility. Controls (N = 262) were women in whom the infertility remained unexplained after a diagnostic laparoscopy. Selected characteristics were documented by means of a face-to-face interview before the laparoscopy. The prevalence of minimal or mild endometriosis was higher in women age 25 years or older, in those who reported menarche at the age of 13 years [prevalence odds ratio (POR) = 1.63; 95% confidence interval (CI) = 1.02-2.60] or older (POR = 1.73; 95% CI = 1.07-2.78), menstrual cycles of 27 days or less (POR = 1.63; 95% CI = 1.02-2.60), or caffeine intake of 300 mg per day or more (POR = 1.33; 95% CI = 0.91-1.94). The prevalence of minimal or mild endometriosis was inversely related to body mass index. Parous women were less likely to have endometriosis (POR = 0.61; 95% CI = 0.39-0.96) than were nulliparous women. Education, duration of infertility, and smoking status were not related to the presence of endometriosis.

Adult↗