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PubMed1997

Differential expression of IGF-I and IGF-II in eutopic and ectopic endometria of women with endometriosis and in women without endometriosis.

PROBLEM: Factors regulating the development, growth, and differentiation of endometrial cells of endometriotic lesions are poorly understood. To investigate the paracrine-autocrine regulation of ectopic endometrial cell growth, the expression of IGF-I and IGF-II were studied. METHOD: Tissue specimens of eutopic and ectopic endometria were obtained from eight patients with endometriosis at laparoscopy and from the endometria of 14 women without endometriosis as controls. They were tested for the expression of IGF-I and IGF-II by immunohistochemical analysis. RESULTS: Immunohistochemical study for IGF-I in controls showed a more intense staining during the proliferative phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis a reduction in the staining was observed, whereas in epithelial cells of fibrotic peritoneal adhesions an intense immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in controls showed a more intense staining during secretory phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis, a reduction in the staining was observed, whereas in epithelial cells of fibrotic peritoneal adhesions an intense immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in controls showed a more intense staining during secretory phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis, a reduction in the staining was observed, whereas in epithelial cells of ovarian lesions and fibrotic peritoneal adhesions, no immunostaining for IGF-II was observed. CONCLUSIONS: In endometriosis there is an alteration of mechanisms regulating cell proliferation and differentiation.

Endometriosis↗
PubMed1987

Altered progesterone/estrogen receptor ratios in endometriosis. A comparative study of steroid receptors and morphology in endometriosis and endometrium.

In a comparative study of endometriosis and endometrium, specimens were taken from both endometriotic and endometrial tissue in 14 patients. Receptor assays and histological examinations were performed on both specimens. Cytosolic estrogen receptors (ERc) as well as cytosolic progesterone receptors (PRc) were detected in 9/14 and 12/12 cases of endometriosis respectively. Nuclear estrogen receptors (ERn) were detected in 4/4 cases of endometriosis. Expressed as fmol/mg cytosol protein, significantly higher values of both ERc and PRc were found in endometrium than endometriosis (p less than 0.01). However, when the ratio between PRc and ERc was considered, significantly higher PRc/ERc ratios were found in the cytosol of endometriotic tissue (p less than 0.01). Thus the lower receptor concentrations found in endometriosis cannot be explained solely as ectopic endometrium being diluted by nonreceptor-containing tissue. In spite of high PRc/ERc ratios in endometriosis, secretory changes similar to those found in endometrium were observed in only one of 7 cases (p less than 0.05).

Adult↗
PubMed1991

Nucleolar organizer regions in endometriosis, atypical endometriosis, and clear cell and endometrioid carcinomas.

Nucleolar Organizer Regions (NORs) code for ribosomal RNA and are thought to be an accurate representation of the percentage of cells in S-phase. NORs are associated with nonhistone nucleoproteins, which can be stained with silver (AgNORs). An increased number of AgNORs has been observed in many malignancies. AgNORs were counted in three groups of patients with endometriosis (Group I), atypical endometriosis (Group II), and clear cell or endometrioid carcinomas (Group III) to assess the malignant potential of atypical endometriosis. Each group consisted of 10 patients. Mean AgNOR counts were 5.83 (Group I), 7.68 (Group II), and 15.42 (Group III). The results were analyzed and were significantly different for all groups (P less than 0.05 for Groups I and II, P less than 0.02 for Groups II and III, and P less than 0.01 for Groups I and III). A critical AgNOR count of 8.20 was calculated utilizing AgNOR counts from Group I. Three of the four patients with AgNORs greater than 8.20 and atypical endometriosis developed a malignancy. AgNOR counts provide useful information, represent an inexpensive test which can be obtained from fixed tissue, and may aid in clinical management of patients with atypical endometriosis.

Adenocarcinoma↗
PubMed2005

Endometrioid adenocarcinoma with squamous differentiation arising from ureteral endometriosis in a patient with no history of gonadal endometriosis.

BACKGROUND: Malignant transformation may occur in up to 1% of women with endometriosis and only 20% of these cases occur at extragonadal pelvic sites. Similarly, urinary tract endometriosis is rare and occurs in only 1% of all endometriotic lesions. CASE: An endometrioid carcinoma with squamous differentiation arising from periureteral endometriosis presented as a pelvic mass encasing the right ureter. The patient had a history of total hysterectomy and bilateral salpingo-oopherectomy 8 years earlier because of bilateral serous benign cysts with right hemorrhagic corpus luteum and uterine fibroids, and has since been under unopposed estrogen replacement therapy for 5 years. CONCLUSION: This is the second case of a malignancy arising in endometriosis presenting as an obstructive ureteral mass and the first case of a patient with this condition whose endometriosis is not consistent with a gonadal origin. An analysis of the case and related literature is presented together with the discussion of possible pathogenetic mechanisms.

Carcinoma, Endometrioid↗
PubMed1992

An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team.

OBJECTIVE: To compare the efficacy and safety of goserelin depot and danazol for endometriosis. DESIGN: Open, randomized comparative trial. SETTING: Multicenter European academic clinical institutions. PATIENTS: A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy. INTERVENTIONS: A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks. MAIN OUTCOME MEASURES: Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures. RESULTS: There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol. CONCLUSIONS: The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d.

Adolescent↗
PubMed1998

Bladder endometriosis: deep infiltrating endometriosis or adenomyosis?

OBJECTIVE: To describe the anatomopathologic characteristics of endometriosis infiltrating the bladder detrusor. DESIGN: Descriptive anatomopathologic study. SETTING: Tertiary care center for endometriosis. PATIENT(S): Four patients, aged 22-38 years, who underwent laparotomy for bladder endometriosis. INTERVENTION(S): Surgical excision and pathologic analysis of bladder endometriotic nodules in four patients. MAIN OUTCOME MEASURE(S): Gross and microscopic characteristics of endometriotic nodules. RESULT(S): A nodule of adenomyosis on the anterior wall of the uterus, in continuity with the detrusor lesion, was excised in three patients. In the other patient, bladder endometriosis was continuous with a nodule that infiltrated the left parametrium and extended as far as the posterior leaf of the ipsilateral broad ligament. Microscopically, all of the lesions had a similar histologic pattern: foci of endometriosis scattered in the bladder wall. The main feature was the paucity of endometrial-type stroma, particularly in the bladder submucosa, where glands were almost always dilated and cystlike and were lined by flattened cells. CONCLUSION(S): Analysis of our patients, although it does not pinpoint the pathogenesis of the disease, seems to exclude the hypothesized intraperitoneal origin of endometriotic lesions of the bladder detrusor.

Adult↗
PubMed1983

Endometriosis of the ureter can present as renal failure: a case report and review of endometriosis affecting the ureters.

Of the female subjects with pelvic endometriosis 1.2 per cent are found to have involvement of the genitourinary tract. Ureteral obstruction secondary to endometriosis is uncommon and usually is unilateral. We report a case of renal failure with hypertension due to bilateral ureteral obstruction from pelvic endometriosis. Ureteral endometriosis and its treatment are discussed. In premenopausal women presenting with bilateral obstruction of the distal ureters endometriosis should be part of the differential diagnosis.

Acute Kidney Injury↗
PubMed2003

Serum concentrations of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines.

Endometriosis is a common gynecologic syndrome of unknown etiology and pathogenesis. Growth factors and inflammatory mediators produced by peritoneal leukocytes have recently been postulated to participate in the pathogenesis of endometriosis. Angiogenic factors released from peritoneal macrophages may also play a role in the development of this disease. In the present study, we investigate the soluble levels of vascular endothelial growth factor (VEGF), epidermal growth factor-receptor (EGF-R), granulocyte/macrophage-colony stimulating factor (GM-CSF), Insulin-like growth factor-1 (IGF-1) and interferon-gamma (IFN-gamma) in the serum of 28 women with and 20 without endometriosis. We also compared these levels before, during and after treatment with danazol and leuprorelin acetate depot, the two therapeutic regiments of choice concerning this disease. We found that only sVEGF levels were higher in women with endometriosis in comparison to controls (P < 0.001) while sEGF-R is not present. GM-CSF, IGF-1 and IFN-gamma soluble levels are not affected in either healthy or endometriotic subjects. The 6-month treatment with danazol decreased sVEGF levels (P < 0.02) and increased sEGF-R levels (P < 0.001). These observations support the view that VEGF may be associated with the disease process and that danazol may bring sVEGF levels to a normal threshold. However, future studies will be focused on the anti-angiogenic control of the action of VEGF in patients with endometriosis.

Adult↗
PubMed2006

Measuring quality of life in women with endometriosis: tests of data quality, score reliability, response rate and scaling assumptions of the Endometriosis Health Profile Questionnaire.

BACKGROUND: To test the data quality, scaling assumptions and scoring algorithms underlying the Endometriosis Health Profile-30 (EHP-30) questionnaire: a questionnaire developed to measure the health-related quality of life (HRQoL) of women with endometriosis. METHODS: A cross-sectional postal survey to 727 women with surgically confirmed endometriosis recruited from an existing genetic linkage study (OXEGENE), The National Endometriosis Society (NES), UK and the outpatient gynaecology clinics of the Women's Centre, John Radcliffe Hospital, Oxford. Tests of data quality included secondary factor analysis, internal reliability consistency, descriptive statistics of the data, missing data levels, floor and ceiling effects and corrected item to total correlation scores. RESULTS: Six hundred and ten women (83.9%) returned the questionnaire. Secondary factor analysis verified the domain structure of the EHP-30. All 11 dimensions were internally reliable with Cronbach's alpha scores ranging from 0.80 to 0.96. Missing response rates ranged from 0.2 to 1.3%, and all items were found to be most highly correlated with their own (corrected) scale. CONCLUSIONS: Results confirmed the factor structure, scoring and scaling assumptions of the questionnaire. The high rate of data completeness indicated that the EHP-30 was acceptable and understandable to the respondents, thereby verifying its suitability for measuring the HRQoL of women with endometriosis.

Adolescent↗
PubMed1996

Expression of the 60 kDa heat shock protein in peritoneal fluids from women with endometriosis: implications for endometriosis-associated infertility.

Proinflammatory cytokines and activated macrophages and T lymphocytes have been detected in peritoneal fluids of women with endometriosis and may impair fertility. Expression of the 60 kDa heat shock protein (hsp60) is one mechanism leading to a localized activation of macrophages and T lymphocytes and cytokine release. Peritoneal fluids, obtained from 68 women undergoing a diagnostic laparoscopy, were assayed for hsp60. As independent evidence of local immune activation, the fluids were analysed for interferon gamma (IFN gamma). Fluids were also tested for antibodies to Chlamydia trachomatis because a chronic asymptomatic infection by this organism may also release hsp60. At laparoscopy, 26 women were diagnosed with pelvic adhesions, 19 had endometriosis, 16 had a visibly normal pelvis, four had ovarian cysts while three had myomas. The prevalence of hsp60 was higher in peritoneal fluids from the women with endometriosis than in the other subjects (P = 0.005). Hsp60 was detected in seven (36.8%) of the endometriosis patients and in only one each of the women with adhesions, a normal pelvis or an ovarian cyst; all women with myomas were negative. Detection of IFN gamma in peritoneal fluids was highly correlated with the presence of hsp60 (P = 0.0003). IFN gamma was present in seven of nine (77.8%) women with hsp60 and in only five of 40 (12.5%) women lacking hsp60. Women with pelvic adhesions had an increased prevalence of immunoglobulin G antibodies to C.trachomatis compared with the other women (P = 0.01). There was no relationship between evidence of exposure to C.trachomatis and hsp60 in peritoneal fluids. These data suggest that hsp60 may be released into the peritoneal fluid as a consequence of implanted ectopic endometrium. Hsp60-mediated immune activation may be one mechanism leading to endometriosis-associated infertility.

Adult↗
PubMed2002

Ovarian endometriosis and peritoneal endometriosis: are they different entities from a fertility perspective?

This review summarizes the recent literature concerning new data on the pathogenesis of peritoneal endometriosis and its natural evolution. Indeed, the main concern in endometriosis is the choice of treatment in cases of infertility problems: medical or surgical. This concern could hypothetically be avoided if endometriosis were considered as a spontaneously regressive phenomenon. The present paper also discusses the risk of recurrence and the results of in-vitro fertilization and embryo transfer in cases of ovarian endometriosis. Whatever type of surgery is performed, the results of in-vitro fertilization and embryo transfer are not impaired, especially if damage to the ovarian cortex is avoided. Further studies are required to determine if oocytes from endometriosis patients are altered and could be responsible for the development of lower quality embryos.

Endometriosis↗
PubMed1998

Increased mast cell density in peritoneal endometriosis compared with eutopic endometrium with endometriosis.

PROBLEM: Factors regulating fibrosis in peritoneal endometriosis are poorly understood. We hypothesized that mast cell proteases may play a role in the process of fibrosis in peritoneal endometriosis. As the first step in examining the possible contribution of mast cells to fibrosis, we investigated their distribution in peritoneal endometriosis lesions according to their macroscopic appearance. METHOD OF STUDY: Mast cells were identified by immunohistochemistry using monoclonal antibody against mast cell tryptase on formalin-fixed, paraffin-embedded sections. Mast cell density (mean mast cell count per 0.13 mm2 of stroma) was measured using a computerized image analysis system. RESULTS: Mast cell density was significantly increased in black peritoneal lesions compared with red peritoneal lesions in endometriosis. CONCLUSIONS: Mast cells may be involved in the pathogenesis of peritoneal endometriosis.

Chymases↗
PubMed1986

Endometriosis and genital anomalies: some histogenetic aspects of external endometriosis.

Six cases with a coexistence of endometriosis and genital anomalies among 112 patients with external endometriosis and 90 patients with genital anomaly were detected. Three cases of severe endometriosis associated with uterovaginal duplication, unilateral renal agenesis and ipsilateral blind vagina and the latter in a patient with Rokitansky-Kuster-Hauser syndrome are presented. Another case with obstructive genital anomaly without endometriosis is also presented. The histogenetic mechanisms of endometriosis are discussed. The transplantation theory is not sufficient to explain all the cases and, therefore, the theory of celomic metaplasia and the theory of müllerian remains or Cullen's theory, as well as the intervention of genetic-constitutional, immunologic, hormonal and other factors must also be considered.

Adolescent↗
PubMed2002

Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice.

The cyclic expression of matrix metalloproteinases (MMPs) by human endometrium has been suggested to play a role in the invasive process necessary to establish endometriosis. The ability of progesterone exposure to inhibit endometrial MMP-3 and MMP-7 expression requires the local action of TGF beta and may also be linked to the local production of retinoic acid by stromal cells. A continuous expression of several MMPs in endometriotic lesions has been reported, indicating a failure of progesterone or locally produced factors to suppress these enzymes. To address cell-specific MMP regulation associated with endometriosis, we examined expression of MMP-3 and MMP-7 mRNA in eutopic endometrium and endometriotic lesions acquired during the secretory phase of the menstrual cycle. We examined the in vitro regulation of MMP-3 and MMP-7 protein in similar tissues. We also examined the in vitro regulation of MMP secretion by progesterone, retinoic acid, and TGF beta in endometriosis tissues relative to the establishment of experimental disease. Our studies indicate that either eutopic or ectopic tissue from women with endometriosis exhibit patterns of altered MMP regulation in vivo. A lack of responsiveness to progesterone was demonstrated in vitro, associated with a failure to suppress MMP expression and an enhanced ability of the tissue to establish experimental endometriosis. However, in vitro treatments with retinoic acid and TGF beta restored the ability of progesterone to suppress MMPs in vitro and prevented the establishment of experimental disease.

Adolescent↗
PubMed1994

Prevalence and anatomical distribution of endometriosis in women with selected gynaecological conditions: results from a multicentric Italian study. Gruppo italiano per lo studio dell'endometriosi.

We have evaluated the prevalence of endometriosis in selected gynaecological conditions requiring surgery. Eligible for the study were women with primary or secondary sterility, chronic pelvic pain, fibroids or benign ovarian cysts requiring laparoscopy or laparotomy consecutively observed during the study period in 23 obstetrics and gynaecology departments in Italy between May 1991 and July 1992. Women with a previous diagnosis of endometriosis were specifically excluded. A total of 3684 subjects entered the study. Of these, 660 (mean age 31 years) were included for sterility, 409 (mean age 32) for chronic pelvic pain, 1880 (mean age 42) for fibroids and 735 (mean age 33) for benign ovarian cysts. During the surgical procedure surgeons were asked to examine the pelvis carefully to identify endometriosis. Out of the 660 women included for sterility, 195 [30%, 95% confidence interval (CI) 26-35] had endometriosis; the corresponding figures were 185 out of 409 (45%, 95% CI 39-52) for pelvic pain, 219 out of 1880 (12%, 95% CI 10-14) for fibroids and 257 out of 735 (35%, 95% CI 31-40) for ovarian cysts; these differences were significant (chi2(3) heterogeneity, absence versus presence = 323.9, P < 0.001). Among women with endometriosis who entered the study for sterility, 51% were at stage 1, 22% at stage 2, 20% at stage 3 and 7% at stage 4. The corresponding figures for pelvic pain and fibroids were largely similar: 37%, 24%, 30%, 10% for women with pelvic pain, 36%, 11%, 45% and 8% for those with fibroids, but among cases with ovarian cysts stage 3 was over-represented (62% of cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Zoladex (goserelin acetate implant) in the treatment of endometriosis: a randomized comparison with danazol. The Zoladex Endometriosis Study Group.

OBJECTIVE: To compare the efficacy, endocrine effects, and safety of Zoladex (goserelin acetate) and danazol in the treatment of premenopausal women with endometriosis in a multicenter, randomized, open study. METHODS: Three hundred fifteen patients with stages I-IV endometriosis (revised American Fertility Society [AFS] classification) were treated with Zoladex, 3.6 mg every 28 days by subcutaneous injection, or danazol, 400 mg orally twice daily for 24 weeks. Efficacy was assessed by determination of pelvic signs and symptoms scores and revised AFS endometriosis scores. Endocrine effects were determined by measurements of hormone levels. Safety was evaluated by physical examination, laboratory indices, occurrence of adverse events, and bone mineral density changes. RESULTS: Both treatments significantly (P < .0001) reduced mean subjective signs and symptoms scores both during and after therapy. The mean percent reduction in the revised AFS endometriosis score after 24 weeks of treatment was 53% for Zoladex and 33% for danazol, and reduction in the endometrial implants score was 56% for Zoladex and 46% for danazol. Serum estradiol levels decreased to the postmenopausal range in the Zoladex group and to the early follicular phase range in the danazol group. Hypoestrogenic effects occurred more frequently with Zoladex, whereas androgenic side effects were more common with danazol. There was a higher percentage of withdrawals due to adverse events with danazol than with Zoladex. Mean bone mineral density decreased from baseline by 5.4% in the Zoladex group and increased by 1.0% in the danazol group at the end of treatment. CONCLUSION: Zoladex is as well tolerated and as effective as danazol in the treatment of premenopausal women with endometriosis.

Administration, Oral↗
PubMed1996

Fluorescence and photosensitization of experimental endometriosis in the rat after systemic 5-aminolevulinic acid administration: a potential new approach to the diagnosis and treatment of endometriosis.

OBJECTIVE: Our purpose was to evaluate and compare the conversion of 5-aminolevulinic acid into the endogenous photosensitizer protoporphyrin IX in experimentally induced endometriosis and in other normal tissues in a rat model. STUDY DESIGN: Fluorescence of experimental endometriotic lesions, uterus, peritoneum, bowel mesentery, bladder, eye, skin, and skeletal muscle was assessed 3 hours after either intravenous, oral, or intrauterine administration of 5-aminolevulinic acid with use of spectrophotofluorometry. In another experiment the fluorescence of surgically induced endometriosis and adjacent normal peritoneum was evaluated every 15 minutes after 5-aminolevulinic acid administration to assess the time course of protoporphyrin IX production. RESULTS: In the rat endometriosis model intralesional and systemic 5-aminolevulinic acid produced fluorescence within implants showing viable endometrial cells. Treatment with 5-aminolevulinic acid produced low-intensity fluorescence in peritoneum, bowel mesentery, and eye. Relatively intense fluorescence was seen in skin, bladder, and uterus. No fluorescence was observed in skeletal muscle. The intensity of fluorescence varied with the dosage and route of administration of 5-aminolevulinic acid. Fluorescence intensity of protoporphyrin IX was significantly greater in implants than in adjacent normal peritoneum between 2 and 4 hours after treatment. CONCLUSIONS: Protoporphyrin IX fluorescence in experimentally induced endometriosis lesions after intravenous and oral delivery of 5-aminolevulinic acid was significantly greater than the fluorescence detected in adjacent normal peritoneum.

Aminolevulinic Acid↗
PubMed1991

Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain.

In a 3-year prospective study of 643 consecutive laparoscopies for infertility, pelvic pain, or infertility and pain, the pelvic area, the depth of infiltration, and the volume of endometriotic lesions were evaluated. The incidence, area, and volume of subtle lesions decreased with age, whereas for typical lesions these parameters and the depth of infiltration increased with age. Deeply infiltrating endometriosis was strongly associated with pelvic pain, women with pain having larger and deeper lesions. Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class, considerations for a simplifying revision with inclusion of deep lesions are suggested. In conclusion, suggestive evidence is presented to support the concept that endometriosis is a progressive disorder, and it is demonstrated that deep endometriosis is strongly associated with pelvic pain.

Aging↗