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PubMed1997

Prevalence of ovarian endometriosis in epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to examine the occurrence of ovarian endometriosis in epithelial ovarian cancer in Japan. METHOD: The presence of ovarian endometriosis was determined by reviewing the sections of resected specimens in 172 epithelial ovarian cancers. RESULTS: The incidence of ovarian endometriosis in ovarian cancer (14.5%) was higher than that in Western countries. The rank order of incidence of endometriosis in each histologic type was clear cell (40.6%)>endometrioid (23.1%)>serous (8.7%)>mucinous (2.9%). The incidence in serous type was higher when compared with that reported in Western countries. The higher incidence of endometriosis in Japan can be explained by a greater proportion of clear cell type, comprising 18.6% of all the cases and a higher incidence of endometriosis in the serous type. CONCLUSION: The association of ovarian endometriosis with epithelial ovarian cancer was more frequently found in Japan.

Adenocarcinoma, Clear Cell↗

PubMed2003

Left lateral predisposition of endometriosis and endometrioma.

To evaluate lateral distribution of endometriosis and ovarian endometrioma in women with endometriosis. We evaluated operative reports of women who underwent laparoscopic treatment of endometriosis (n = 330) and ovarian endometrioma (n = 185) from January 1996 to January 2002. Data on all operative findings consisted of a written report, a diagram, the revised American Fertility Society classification of endometriosis, and a printout of the dictated report. Endometriotic implants were confined to one side of the pelvis in 143 women and bilaterally in 187 others. Endometriosis was significantly more frequent in the left (64.3%) than in the right hemipelvis (P <.001, odds ratio 3.3, 95% confidence interval 2.0, 5.3). Of those with bilateral lesions, adhesions were also more frequently found on the left than on the right hemipelvis (16.6% versus 6.9%, P <.01, odds ratio 2.6, 95% confidence interval 1.3, 5.2). Endometrioma was found in the left ovary (n = 90), in the right ovary (n = 59), and bilaterally (n = 36). Left ovarian endometrioma was found more frequently (60.4%) than right endometrioma (P <.001, odds ratio 2.3, 95% confidence interval 1.5, 3.7). This trend was not related to the size of the endometrioma.Our results confirm a left lateral predisposition of endometriosis and ovarian endometrioma. It is possible that this is related to decreased fluid movement in the left side of the pelvis because of the presence of sigmoid colon. These findings may support the theory that the origin of endometriosis is from the regurgitated endometrial cells.

Adult↗

PubMed1997

Menstrual characteristics in women with and without endometriosis.

OBJECTIVE: To assess menstrual blood loss and other menstrual characteristics prospectively in women with and without endometriosis. METHODS: Three hundred fifteen premenopausal women undergoing laparoscopy for various reasons were asked to complete a pictorial blood loss assessment chart devised by Higham et al to evaluate menstrual flow on which the monthly score has been demonstrated to correlate directly with uterine blood loss measured by the alkaline hematin method. In addition, cycle length and flow duration were recorded. The women also were asked to grade dysmenorrhea severity using a 100-mm visual analogue and a 0-3-points verbal rating scale. RESULTS: One hundred sixty-three women had endometriosis, and 152 did not. The latter group comprised 59 women with a normal pelvis, 36 with nonendometriotic ovarian cysts, 29 with chronic pelvic inflammatory disease, and 28 with miscellaneous conditions. The median [interquartile range] pictorial blood loss assessment chart score was 110 [66.5-156.5] in women with endometriosis and 84 [56-129] in those without the disease (P = .007); 87 out of 163 (53%) women with endometriosis had a menstrual chart score equal to or greater than 100 compared with 56 out of 152 (37%) of those without (chi 2(1) = 8.02, P = .005; difference = 16%, 95% confidence interval, 6%, 28%). Menstrual flow duration was slightly longer in women with endometriosis (mean difference, 0.33 days). Dysmenorrhea visual analogue and verbal rating scores were significantly higher in the endometriosis than the nonendometriosis group. CONCLUSION: According to a visual chart, women with endometriosis had heavier menstrual flow and a significantly higher rate of abnormal menstrual scores that those without the disease.

Adult↗

PubMed1999

Progesterone and transforming growth factor-beta coordinately regulate suppression of endometrial matrix metalloproteinases in a model of experimental endometriosis.

Endometriosis is a benign, though aggressive, disease of the female reproductive tract that consists of endometrial stromal and epithelial cells growing at an extrauterine site. Although it is widely accepted that the majority of cases of endometriosis result from the ectopic implantation of refluxed menstrual tissue, the precise mechanisms by which this disease becomes established are not well understood. Matrix metalloproteinases (MMPs), enzymes which are important for extracellular matrix turnover, have recently been implicated in the development of endometriosis. MMPs appear to be overexpressed in endometriotic lesions, but expression levels decrease following successful medical therapy. Intriguingly, although transforming growth factor-beta (TGF-beta) mediates progesterone suppression of specific endometrial MMPs, this growth factor is overexpressed in women with endometriosis. In the current study, we used an established experimental model of endometriosis to explore MMP regulation by TGF-beta. Our findings indicate that blocking the action of TGF-beta opposes progesterone-mediated suppression of MMPs and blocks the ability of this steroid to prevent experimental endometriosis. However, we also show that the action of TGF-beta does not lead to a sustained suppression of MMPs as observed following progesterone treatment. Taken together, our data suggest that in the absence of a normal progesterone response, common in ectopic lesions of endometriosis, sensitivity to TGF-beta may be altered, resulting in a failure to regulate MMPs.

Adult↗

PubMed2003

The current staging system for endometriosis: does it help?

A multicenter collaboration for data collection and statistical analysis may be necessary to establish and validate a classification system based on empirically derived scores for specific pathologic observations. The endometriosis pain instrument may be a tool for some of those variables with regard to pelvic pain. A similar strategy for uniform collection of data for analysis of important factors also is necessary for infertility. The challenge of creating a satisfactory classification of endometriosis remains. The ability of the current classification schemes to predict pregnancy outcome or aid in the management of pelvic pain is recognized to be inadequate. Further revisions of the current classification scheme are anticipated as the understanding of how endometriosis contributes to infertility and pelvic pain evolves. In any revision of the classification system, use of empirically derived weights and breakpoints to define disease stages based on outcome data in larger clinical trials should be attempted. It is also possible that additional factors, such as CA-125 level or lesion characteristics, may be shown to play an important role in prognosis. If so, these must be accounted for in the classification scheme. Careful and consistent use of the recommendations of the American Society for Reproductive Medicine classification of endometriosis subcommittee should allow for collection of data for use in further revisions. It is possible that a classification scheme that is designed to predict outcome with respect to pregnancy may be totally inadequate in assessing patients who have endometriosis and pelvic pain. Factors found to be important in the assessment of pelvic pain may be different from those involved with the pathophysiology of endometriosis and infertility. The AFS form suggested for use in the management of endometriosis in the presence of pelvic pain allows for recording of variables such as depth of invasion, histology, and documenting adjunct investigations and preoperative physical findings. Such prospective data collection and review in large centers may provide a large clinical base from which to derive empirical point scores and breakpoints in a classification scheme.

Endometriosis↗

PubMed1994

Endoscopy in the management of endometriosis.

Endoscopy has replaced laparotomy in nearly all patients requiring surgical treatment of endometriosis. Controlled trials have shown electrosurgery is more effective than expectant treatment in the resolution of infertility due to peritoneal endometriosis and equally effective as laparotomy. Laparoscopy surgery reduces patient morbidity and costs when compared with laparotomy. No significant difference has been demonstrated between laser or electrosurgery in resolving infertility related to peritoneal endometriosis. Peritoneal endometriosis is difficult to diagnose and its extent is obscured by occult endometriosis in microscopic foci. Biopsy is required to establish the diagnosis as all of the described lesions of endometriosis may also be due to other diseases. Excision of the lesions may be by electrosurgery, laser or scissor diathermy. Scissor diathermy has advantages over laser or electrosurgery. Endometriomas may be removed by one- or two-stage excisional surgery. Follow-up laparoscopy is often indicated because of the association with secondary adhesive formation. Pouch of Douglas endometriosis requires special attention to the identification of the extent of disease and the technique of removal. Rectal involvement may require rectal surgery, most of which can be achieved by laparoscopy. Hysterectomy and oophorectomy may be performed laparoscopically and are indicated for recurrent extensive disease not controlled by medical or conservative surgical procedures, for adenomyosis or for extensive pelvic adhesions.

Endometriosis↗

PubMed1997

Epidemiologic determinants of endometriosis: a hospital-based case-control study.

PURPOSE: Risk factors for endometriosis were identified through data obtained from a case-control study at Brigham and Women's Hospital in Boston, Massachusetts. METHODS: Cases were 50 women with infertility-associated endometriosis. The primary control group consisted of 89 fertile women without endometriosis, and an alternate control group consisted of 47 infertile women without endometriosis. RESULTS: The risk of endometriosis was positively associated with height (OR), 2.8 per 10 cam increase; 95% confidence interval (CI), 1.4-5.6) and inversely associated with weight (OR, 0.7 per 10 kg increase; 95% CI, 0.5-1.0) and body mass index (OR, 0.7 per 5 kg/m2 increase; 95% CI, 0.4-1.1). We observed an inverse association with exercise (OR, 0.6; 95% CI, 0.3-1.5), but the effect was limited to women who exercised > or = 4 hours per week (OR, 0.4; 95% CI, 0.2-1.2). Endometriosis was not associated with either smoking or alcohol consumption. CONCLUSIONS: Our findings suggest that the fertility status of controls can strongly influence associations seen with menstrual characteristics. This study is one of few to address the issue of control selection for a case-control study of endometriosis. Specifically, potential problems encountered using fertile and infertile control women are examined and discussed.

Adult↗

PubMed1997

The outcome of in vitro fertilization and embryo transfer therapy in women with endometriosis failing to conceive after laparoscopic conservative surgery.

STUDY OBJECTIVE: To compare the outcome of in vitro fertilization and embryo transfer (IVF-ET) after laparoscopic surgery in women with endometriosis with that of patients with tubal factor infertility. DESIGN: Retrospective survey of hospital and office charts using a computerized worksheet. SETTING: Lin-Kou medical center of Chang Gung Memorial Hospital. PATIENTS: Sixty-seven women with minimal to mild or moderate to severe endometriosis. Women with tubal factor infertility without other associated disorders (60 cycles) made up the control group. INTERVENTIONS: Seventy-five consecutive cycles of IVF-ET were performed in these patients who failed to conceive after laparoscopic conservative surgery. MEASUREMENTS AND MAIN RESULTS: The concentration of serum estradiol on the day of human chorionic gonadotropin (hCG) injection, the day of hCG injection, clinical pregnancy rates per transfer, number of follicles larger than 14 mm, number of embryos transferred, and implantation rate were not significantly different between women with endometriosis and those with tubal factor infertility. The number of oocytes retrieved and number fertilized were decreased, and the basal level of follicle-stimulating hormone on cycle day 3 was higher in women with both degrees of endometriosis. Women in both endometriosis groups received more follicle-stimulating hormone and human menopausal gonadotropin than those with tubal factor infertility. CONCLUSIONS: The outcome of IVF-ET in patients with endometriosis after laparoscopic surgery did not differ from that in the group with tubal factor infertility, but the former required more ampules of gonadotropin to achieve the same response. The advantages of laparoscopic surgery in women with endometriosis should be probably correlated with success of IVF-ET.

Adult↗

PubMedDate not supplied

Endometriosis: an overview of the disease and its treatment.

OBJECTIVE: To review endometriosis, its etiology, clinical presentation, and current management options. DATA SOURCES: Published articles identified through MEDLINE (1966-2000) using the search term "endometriosis" and the additional terms "etiology" and "treatment." Additional articles were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: Endometriosis, a disease that affects the physical health and emotional well-being of many women of reproductive age, is defined as the presence of endometrial tissue outside its normal location in the uterus. The disease ranges in severity from mild to severe, and patients may be asymptomatic or experience severe and potentially incapacitating symptoms, such as dysmenorrhea, dyspareunia, and infertility. The diagnosis can be confirmed only by direct visualization using laparoscopy and biopsy. The risk of endometriosis is increased in women who have an affected first-degree relative or who have shorter menstrual cycle lengths, longer duration of menstrual flow, and low parity. The etiology of endometriosis is not yet fully understand, but may involve retrograde menstruation, hereditary factors, and impaired immune function. Treatment should be individualized for each patient, taking into account the therapeutic goals, the extent of disease, symptomatology, and the woman's age and overall health. Treatment options include expectant management, hormonal therapies to suppress ovarian steroidogenesis and induce endometrial atrophy, and surgery to remove visible lesions or, as a last resort, the uterus and ovaries. CONCLUSION: Although the precise etiology of endometriosis remains a mystery, treatment options have improved considerably in recent years. Pharmacists are well positioned to identify women with unexplained pelvic pain or infertility that may be indicative of endometriosis and refer them to their physicians for further evaluation. Pharmacists also can play an important role in counseling patients about the safe and effective use of the various treatments for this disease and strategies to recognize and reduce adverse effects.

Endometriosis↗

PubMed2006

Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?

Endometriosis is more frequently diagnosed in patients with infertility than in a normal population. The goal of this paper is to give an overview of the clinical and fundamental evidence for a possible link between endometriosis and (recurrent) miscarriage or implantation failure after treatment with assisted reproductive technology. According to the literature, there is insufficient evidence for an association between endometriosis and (recurrent) miscarriage, but there is, however, epidemiological evidence to support the link between endometriosis and recurrent implantation failure after assisted reproduction. This can possibly be explained by alterations in humoral and cell-mediated immunity in women with endometriosis. Humoral immunological changes include increased formation of antibodies against endometrial antigens, anti-laminin-1 auto-antibodies and other auto-immune antibodies (e.g. antiphospholipid). Cell-mediated immunological changes include alterations in peritoneal and follicular fluid immune cells and cytokines. The possible negative effect of these immunological changes on folliculogenesis, ovulation, oocyte quality, early embryonic development and implantation in women with endometriosis suggests that infertility in endometriosis patients may be related to alterations within the follicle or oocyte, resulting in embryos with decreased ability to implant.

Abortion, Habitual↗

PubMed2002

Reproductive disorders affecting fertility in endometriosis.

The classical concept of endometriosis as a cause of infertility is challenged. Traditionally, both surgical and medical therapy of endometriosis-associated infertility has focused on eliminating or reducing the visible implants. The classic 6-month medical approach has been a failure, and surgery may moderately enhance fertility, but its benefit in the absence of adhesions is still doubtful. Recent studies have shown that endometriosis is characterized by an aberrant response to sex steroid hormones, resulting in pleiotropic dysfunctions of the reproductive system involving the uterine, peritoneal and ovarian micro-environment. Studies on endometriosis and IVF have been highly relevant in revealing the pleiotropic dysfunctions in patients with endometriosis, although the results should be interpreted with caution. The conclusion seems to support the view that infertility in patients with endometriosis is primarily dysfunctional, rather than lesional, in origin. It is concluded that the place of medical therapy in endometriosis should be reviewed and that the surgical approach needs to be complemented by appropriate medical therapy to restore fertility.

Endometriosis↗

PubMed2004

Endometriosis-associated ovarian cancer: a clinicopathologic review.

Endometriosis is a common clinical disorder in women and usually presents with pelvic pain, infertility, or adnexal masses secondary to intracystic hemorrhage with the formation of an endometrioma. Endometriosis shares certain characteristics with malignant neoplasms, and malignant ovarian tumours have been documented in women with endometriosis. Endometriosis-associated ovarian cancer (EAOC) usually occurs in younger women, has favourable outcomes, and appears as either a low-grade tumour of endometrioid cell type or as a clear cell tumour. As it has been suggested that the pathologic features of "atypical endometriosis" may constitute a precancerous state, women with atypical endometriosis may be at an increased risk of developing EAOC. There are no prospective randomized trials assessing treatment regimens for EAOC. Most women receive treatment similar to other epithelial ovarian cancers. However, women with EAOC represent a subgroup of patients that may require different therapeutic options. English-language journals indexed in MEDLINE and PubMed were searched for relevant articles that evaluated the association between endometriosis and ovarian cancer, theories of pathogenesis and transformation, the clinical presentation and pathologic features of EAOC, as well as the treatment options available.

Adenocarcinoma, Clear Cell↗

PubMed2003

Increased pregnancy-associated plasma protein-A (PAPP-A) concentrations in peritoneal fluid of women with endometriosis.

PROBLEM: Pregnancy-associated plasma protein-A (PAPP-A) belongs to a group of glycoproteins isolated from extracts of human placenta. Healthy ovarian and uterine tissues are also known to express PAPP-A. We hypothesized that PAPP-A levels might also be elevated in the peritoneal fluid (PF) of women with endometriosis, and examined variations in PF PAPP-A during the menstrual cycle and with the severity of the disease. METHOD OF STUDY: PF PAPP-A were measured in 60 women with endometriosis and 38 women without endometriosis using a high-sensitivity immunofluorometric assay. RESULTS: We found that the mean level of PAPP-A was higher in PF from patients with endometriosis than controls (p = 0.003). Furthermore, significant correlation was found between the stages of endometriosis and the levels of PAPP-A in these patients (r = 0.39, p = 0.009). The concentrations of PAPP-A in PF were significantly higher in the secretory phase than the proliferative phase of the menstrual cycle in both women with and without endometriosis (p = 0.009 and P = 0.002, respectively). Finally, among the controls, women undergoing tubal ligation had significantly lower mean PF levels of PAPP-A than women with infertility or pelvic pain (p = 0.001). CONCLUSION: We conclude that PF levels of PAPP-A vary during the menstrual cycle, and are highest in the secretory phase. We also find that PF PAPP-A levels are significantly increased in women with endometriosis, and that the degree of elevation corresponds to the extent of disease.

Adult↗

PubMed2004

The influence of extracellular matrix proteins on T-cell proliferation and apoptosis in women with endometriosis or uterine leiomyoma.

PROBLEM: Interactions between the extracellular matrix (ECM) and peripheral blood T cells in women with endometriosis and leiomyoma are hardly unknown. We have investigated the influence of two major ECM components, collagen IV (C-IV) and fibronectin (Fn), on T-cell proliferation and apoptosis in women with endometriosis and uterine leiomyoma. beta1 integrin expression, responsible for interactions with ECM proteins, was also studied. METHOD OF STUDY: Peripheral blood lymphocytes were obtained from 53 women (17 with uterine leiomyomas, 18 with endometriosis, and 18 from healthy donors). T cells were exposed to ECM proteins co-immobilized with monoclonal antibody anti-CD3 for 72 hr. Apoptosis and S phase of the cell cycle of the T cells were studied by DNA analysis using flow cytometry. The proliferation of T cells was evaluated by MTT assay. The percentage of CD3+ cells expressing CD29 (beta1 integrin chain) was evaluated by double-color flow cytometry. Results were analyzed statistically using the Mann-Whitney test. RESULTS AND CONCLUSIONS: (1) A general increase in the percentage of T cells in S phase could be seen in women with endometriosis and uterine leiomyoma in all culture conditions what may suggest general activation of T cells. (2) A significant increase in the percentage of cells in S phase was shown only in the case of T cells exposed to anti-CD3 + C-IV in both women with uterine leiomyoma and endometriosis. (3) However, no apoptotic cells were observed. (4) T cells from patients with uterine leiomyoma exhibited significantly increased level of proliferation after culture with anti-CD3 + C-IV. (5) More T cells expressed beta1 integrin in women with endometriosis or uterine leiomyoma than in healthy donors. Our data may suggest that increased beta1 integrin expression may enhance T-cell-ECM interactions, which may be responsible for the increased proliferation of T cells but not for apoptosis. Therefore, it is possible that interactions of T cells with ECM proteins, especially with C-IV, may contribute to the pathogenesis of endometriosis and uterine leiomyoma.

Apoptosis↗

PubMed2003

Environmental dioxins and endometriosis.

Endometriosis is a common gynecologic problem of unknown etiology. Estrogen dependence and immune modulation are established features of this disease, and environmental contaminants have been suggested to play a role in the pathobiology of this disease as well. Previous work in nonhuman primates has shown that exposure to the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with an increased prevalence and severity of endometriosis. Further animal experiments have implicated dioxin and dioxin-like compounds in this disease. Rodent studies support the plausibility of a role of environmental contaminants in the pathophysiology of endometriosis, although a convincing mechanistic hypothesis has yet to be advanced. Small hospital-based case-control studies have failed to provide compelling evidence for or against an association of environmental contaminants and endometriosis. Herein we review evidence that dioxin and dioxin-like compounds are potent modulators of immune and endocrine function critical to the pathobiology of endometriosis. Furthermore, perspectives on the potential mechanism(s) of dioxin and dioxin-like compound-induced toxicity in endometriosis, important knowledge needs, potential animal models for endometriosis studies, and considerations integral to future human case-control studies are discussed.

Animals↗

PubMedDate not supplied

[Endometriosis and malignoma].

Malignant tumors arising from endometriosis are rare. A frequency of about 1% has been reported with in 80% the ovary, and in 20% extragonadal sites being affected. The most common extragonadal manifestations are the rectosigmoid and the rectovaginal septum. For extragonadal malignant tumors arising from endometriosis, complete resection followed by post-operative radiotherapy, possibly plus adjuvant progestin therapy, is the treatment of choice. Endometriosis-associated ovarian carcinomas are likely to present with lower stage disease and predominantly lower grade tumors. While their treatment follows that of common ovarian cancer, a poorer response to chemotherapy must be considered. As unopposed estrogen replacement therapy has been identified as a risk factor for the development of endometriosis-associated cancer, it is not recommended for hormone replacement therapy in women with a history of endometriosis. Loss of heterozygosity and mutations of the PTEN tumor suppressor gene may be early events of tumorigenesis. Endometriosis and its malignant transformation, perhaps, may serve as a suitable model in this regard. According to recent studies, endometriosis is associated with an increased relative risk of non-Hodgkin lymphoma.

Endometriosis↗

PubMed1996

[Significance of tumor necrosis factor alpha (TNF-alpha) in endometriosis].

Macrophage-derived substances such as cytokines and growth promoting factors are known to be present in the peritoneal fluid of women with endometriosis. Active endometriosis of the peritoneum is characterised by hypervascularization and neoangiogenesis. TNF-alpha is a pleiotropic cytokine also involved in angiogenesis and immunoregulation. Our question was to determine whether there are differences in the peritoneal TNF-alpha concentrations in women with various degrees of active and inactive endometriosis. We found that TNF-alpha concentrations were higher in the peritoneal fluid of women with endometriosis than in the peritoneal fluid of those without. TNF-alpha concentrations were higher in cases of active endometriosis than in cases of inactive endometriosis. The highest concentrations could be detected in women with severe endometriosis (stage III and IV rAFS).

Adult↗

PubMed2000

Gonadotropin-releasing hormone analog repairs reduced endometrial cell apoptosis in endometriosis in vitro.

OBJECTIVE: Impaired sensitivity of endometrial tissue to spontaneous apoptosis in women with endometriosis contributes to the abnormal implantation and growth of endometrium at ectopic sites. Our purpose was to examine the effect of gonadotropin-releasing hormone analog, widely used in the treatment of endometriosis, on the reduced rate of endometrial apoptosis in endometriosis. STUDY DESIGN: Paired ectopic and eutopic endometrial tissue specimens were obtained from 13 patients with endometriosis, and control samples were taken from 8 patients with uterine myoma. Apoptotic cell death was assessed biochemically and morphologically with an enzyme-linked immunoassay and Hoechst No. 33342 staining of deoxyribonucleic acid fragment, respectively. RESULTS: Spontaneous apoptosis was significantly lower in ectopic and eutopic endometrial tissue from patients with endometriosis (0.22 +/- 0.082 in absorbance) than in endometrial tissue from control subjects (0.52 +/- 0.483)(P < 0.001). Incubation with a gonadotropin-releasing hormone analog (1 micromol/L) increased the apoptotic rate of endometrial cells from patients with endometriosis to 0.56 +/- 0.501 (P <.001). The effect of this gonadotropin-releasing hormone revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L; however, the control endometrium was not affected. CONCLUSION: Exposure to gonadotropin-releasing hormone results in changes of the sensitivity of endometriotic endometrium to spontaneous apoptosis; these changes in sensitivity may, in turn, release endometrial cells from resistance to apoptosis and result in reduced survival and growth. This phenomenon could, at least in part, account for the therapeutic action of gonadotropin-releasing hormone analog on endometriosis.

Apoptosis↗