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DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection.

Endometriosis, a common gynecological disorder that causes infertility and pelvic pain, is defined as the presence of endometrial glands and stroma within extra-uterine sites. However, despite extensive studies its etiology and pathogenesis are not completely understood. Differentially expressed genes were investigated in epithelial and stromal cells from deep endometriosis and matched eutopic endometrium using cDNA microarrays and laser capture microdissection. Validation of results of several up- and down-regulated genes was performed by quantitative real-time RT-PCR. Our data showed that platelet-derived growth factor receptor alpha (PDGFRA), protein kinase C beta1 (PKC beta1) and janus kinase 1 (JAK1) were upregulated, and Sprouty2 and mitogen-activated protein kinase kinase 7 (MKK7) were downregulated in endometriosis stromal cells, suggesting the involvement of the RAS/RAF/MAPK signaling pathway through PDGFRA in endometriosis pathophysiology. In addition, two potential negative regulators of aromatase expression, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2) and prostaglandin E2 receptor subtype EP3 (PGE2EP3), were downregulated in endometriosis epithelial cells, which might result in increased local production of estrogen in endometriosis epithelial cells. Furthermore, three potential candidate genes that might be involved in endometriosis related pain were identified: tyrosine kinase receptor B (TRkB) in endometriosis epithelial cells, and serotonin transporter (5HTT) and mu opioid receptor (MOR) in endometriosis stromal cells were all upregulated. One of the candidate genes, MOR, may be involved in a defective immune system in endometriosis. This study has provided new insights into endometriosis pathophysiology.

Endometriosis↗

Future perspectives in the medical treatment of endometriosis.

UNLABELLED: In the last few years, our understanding of the pathogenesis of endometriosis at the cellular and molecular levels has improved significantly. This may give us the opportunity to use new, specific agents for the treatment of this disorder. Despite the effectiveness of the available treatments, novel therapeutic strategies may improve our ability to eliminate endometriotic lesions when present and to prevent the recurrence of endometriosis after surgical treatment. This review focuses on the new, experimental approaches to the medical treatment of endometriosis and its symptoms. The blockage of aromatase activity in endometriotic lesions with an aromatase inhibitor may represent a new step in the medical treatment of endometriosis. Preliminary clinical studies have demonstrated the efficacy of third-generation nonsteroidal aromatase inhibitors (ie, anastrozole and letrozole) in reducing the intensity of pain symptoms associated with the presence of endometriosis. The new selective progesterone receptor modulators may represent a valid hormonal treatment option. Therapeutic manipulation of the immune system through TNFalpha inhibitors may be beneficial in women with endometriosis. New pharmaceutical agents affecting inflammation, angiogenesis, and matrix metalloproteinase activity may prevent or inhibit the development of endometriosis. Further clinical trials may determine if these new therapies are superior to current medical treatment strategies for endometriosis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning. OBJECTIVES: After completion of this article, the reader should be able to describe the new experimental medical treatments of endometriosis, state that the clinical use of nonsteroidal aromatase inhibitors for endometriosis appears to be efficacious but is based on preliminary clinical data, and recall that the drugs used for endometriosis in the future may include manipulation of the immune system.

Drugs, Investigational↗

Immune dysfunction--a potential target for treatment in endometriosis.

The treatment approach towards endometriosis has been traditionally either surgical or hormonal in nature. Since endometriosis is, to a large extent, a microscopic disease, a surgical approach cannot be expected to eradicate the disease. Treatment is, therefore, generally attempted by hormonal manipulation, an approach based on the known oestrogen sensitivity of endometriosis. Hormonal manipulation can only temporarily affect endometriosis, and quite clearly does not address the underlying aetiology and/or pathophysiology of the disease. Since neither is, at present, well understood, one can only speculate as to the treatment approach that would, in fact, affect the pathophysiology of the condition. Endometriosis has, in recent years, been characterized by a large number of immunological abnormalities in the host. It is, therefore, very tempting to speculate that an immunological defect represents the basic abnormality which later leads to the occurrence of the disease. This assumption is supported by the observation that those immunological defects are already present in the mildest forms of the disease. In fact, if one believes that many cases of unexplained infertility represent undiagnosed microscopic endometriosis, then evidence suggests that this precursor stage of the disease is basically characterized by an identical immunological profile to that of endometriosis. An immunological aetiology and/or pathophysiology of endometriosis should lead to an immunological treatment approach toward the disease. Specifically, a number of non-specific immunomodulators, presently utilized in a variety of medical conditions with immunological aetiologies, would seem to represent promising new therapeutic strategies to conquer endometriosis at its roots. A new treatment approach to endometriosis appears urgently needed since, at least with regard to the effects of endometriosis on fertility and pregnancy loss, present approaches have proven ineffective.

Autoantibodies↗

Activin-A secretion is increased in the eutopic endometrium from women with endometriosis.

BACKGROUND: Activin is a well-characterised growth and differentiation factor and an important inflammatory mediator. Activin is secreted by normal endometrial glands and stroma and is expressed by endometrial leucocytes. It is also known that the eutopic endometrium from women with endometriosis is functionally different to that from women without endometriosis. In this study, we hypothesise that the endometrial secretion of activin is altered in women with endometriosis. AIMS: To determine whether the expression of inhibin/activin subunits and the secretion of activin-A is different in eutopic endometrium from women with and without endometriosis. METHODS: Endometrial biopsies were obtained from premenopausal, regularly menstruating women with and without endometriosis. Staining intensity for the different inhibin/activin subunits was compared in endometrial and endometriotic biopsies. Activin-A secretion was studied using endometrial explants and endometrial glandular and stromal monolayer cell cultures. RESULTS: The alpha- and betaA-subunits of inhibin/activin were more abundant in eutopic glandular cells from patients with minimal to mild endometriosis compared to women without endometriosis. In patients with endometriosis, the betaB-subunit was more abundant in eutopic stromal cells and endometrial leucocytes. Comparison of paired endometrial and endometriotic biopsies from the same patient did not reveal significant differences for any of the inhibin/activin subunits or activin receptors. Activin-A secretion by glandular and stromal endometrial cells was sevenfold and threefold higher, respectively, in women with endometriosis compared to women without endometriosis. CONCLUSIONS: The expression of inhibin/activin subunits in eutopic endometrium is altered in women with endometriosis, leading to higher levels of activin-A secretion by both glandular cells and stromal cells.

Activins↗

Conventional medical therapies for endometriosis.

Endometriosis is a common gynecologic disorder that affects approximately 14% of all women and 30% to 50% of infertile women. Since the most common symptoms of endometriosis--progressive dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility--are also symptoms of multiple disorders, a diagnosis of endometriosis can be elusive and confirmed only by visualization, that is, laparoscopy. Endometriosis is often treated surgically upon diagnosis; however, the rate of recurrence is high, suggesting that a combination of therapeutic approaches might provide better outcomes than any one option alone. The most widely utilized hormonal treatments for endometriosis are GnRH agonists and oral contraceptives; agents indicated by the Food and Drug Administration include GnRH agonists and the androgen, danazol. The majority of evidence in support of medical therapy for endometriosis is largely observational, with the exception of studies of GnRH agonists, danazol, and a few progestins. Conventional treatment approaches for the medical management of endometriosis focus on suspected endometriosis, following a diagnosis of endometriosis, following surgical treatment of endometriosis, long-term management, and retreatment. Although major advances have been made in the treatment of endometriosis in recent decades, lack of randomized clinical trials evaluating the use of agents such as oral contraceptives alone or as add-back therapy for GnRH agonists, or those that examine combined medical and surgical treatments, has hampered the ability of physicians to provide the broadest range of medical therapies for this disorder. Future trials addressing these issues are warranted.

Danazol↗

Evidence that endometriosis behaves in a malignant manner.

It is well known that certain aspects of endometriosis are similar to those of malignant disease. For example, like cancer, endometriosis can be both locally and distantly metastatic; it attaches to other tissues, invades, and damages them. Endometriosis is a common disease that does not create a cachectic or catabolic state, and is rarely fatal. There are, however, numerous reported cases of malignancy arising from endometriotic deposits and substantial histologic evidence that endometriosis is associated with endometrioid carcinoma and clear cell carcinoma of the ovary. A large review article by Mostoufizadeh and Scully investigated the association between endometriosis and endometrioid carcinoma, noting that women who had both diseases tended to be younger [1]. They found no association between endometriosis and serous or mucinous carcinoma of the ovary, and reported that malignant transformation of endometriosis was rare and associated with the use of exogenous estrogens. An epidemiological study of Swedish women reported a higher incidence of breast and ovarian cancer and non-Hodgkin's lymphoma in women with endometriosis compared with controls [2]. Vercellini and colleagues also reported a higher incidence of endometrioid and clear cell carcinoma in women with endometriosis compared with controls [3]. Mutations in genes associated with galactose metabolism have been identified as one possible mechanism for this association. These mutations are more common in ovarian cancer and have been reported to be more common in women with endometriosis. We compared 78 women with endometriosis with 248 controls and were unable to demonstrate an increased frequency of these mutations in any of these groups.

Animals↗

Genetic Relationship Between Endometriosis and Melanoma.

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (r g = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

endometriosis↗

[Influencing factors of depression in women with endometriosis].

PURPOSE: The purpose of this study was to understand depression in women with endometriosis and to identify the factors influencing depression. METHOD: The instruments used were the Beck Depression Inventory for depression, Lemaire Scale for endometriosis syndrome, Mishel Uncertainty in Illness Scale-Community form (MUIS-C), the Rosenberg Self-esteem Scale, and Quality of Life (Endometriosis Health Profile Questionnaire; EHP-5) by Jones et al. The Subjects of Study were 118 outpatients diagnosed with endometriosis from 7 hospitals in Busan City and Kyungsangnam-do. Data was collected from Aug 1, 2004 to Jan 31, 2005. For statistical analysis of collected data, frequency analysis, analysis of variance, and stepwise multiple regression analysis were used with the SPSS statistical program. RESULT: The general characteristic showing a statistically significant difference in depression in the women with endometriosis was marital status. The score of the depression showed a significantly positive correlation with the score of endometriosis TSD(r= .464, p= .000), uncertainty(r= .393, p= .000), and quality of life(r= .543, p= .000). Depression showed a significantly negative correlation with the score of self esteem(r= - .557, p= .000). Stepwise multiple regression analysis revealed that the most powerful predictor of depression in the women with endometriosis was self-esteem (R2=0.311). A combination of self esteem, quality of life, and total symptom distress accounted for 50.0% of the variance in depression in women with endometriosis. CONCLUSION: The influencing factor on depression in women with endometriosis was self- esteem, quality of life, and endometriosis TSD. Further studies need to be done to identify methods of overcoming and the presentation of depression in endometriosis.

Adult↗

Endometriosis: current management.

OBJECTIVE: To review the clinical features, theories of pathogenesis, and current treatment of endometriosis-associated pain and infertility. DESIGN: We review the manifestation of endometriosis and the possible mechanisms that lead to its symptoms, examine the efficacy of current therapeutic options for pelvic pain and infertility, and provide specific recommendations for treatment based on the current literature. MATERIAL AND METHODS: Endometriosis is the presence of hormonally responsive endometrial tissue occurring outside the uterine cavity. This condition may be asymptomatic but is often found in association with pelvic pain or infertility (or both). The precise pathogenesis has not been clearly established but likely involves retrograde menstruation with subsequent seeding of endometrial glands at extrauterine sites. The definitive diagnosis and staging of endometriosis are performed by laparoscopy. Various strategies have been used to treat endometriosis including expectant, medical, surgical, and combination management. RESULTS: The efficacy of treatment varies for pelvic pain and infertility. Endometriosis-associated pain may respond to both medical and surgical management. The use of medical therapy for endometriosis-associated infertility is not supported by current studies. Surgical management of infertility may be efficacious when pelvic anatomy is distorted because of endometriosis. The use of superovulation strategies and in vitro fertilization has been shown to be effective in overcoming endometriosis-associated infertility. CONCLUSION: Pelvic pain and infertility in the presence of endometriosis necessitate individualization of therapy to achieve treatment goals. Neither medical nor surgical management is efficacious in all circumstances. As a better understanding of the pathogenesis of endometriosis evolves, treatment of this perplexing condition will probably continue to improve.

Adult↗

The cost of inpatient endometriosis treatment: an analysis based on the Healthcare Cost and Utilization Project Nationwide Inpatient Sample.

OBJECTIVE: To determine the prevalence and cost of endometriosis-related hospitalizations based on the Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP-3). STUDY DESIGN: Retrospective analysis based on nationwide clinical practice data. PATIENTS AND METHODS: Data were obtained for 1991 and 1992 from the HCUP-NIS database, which was a 20% sample of all US hospital discharges. ICD-9 codes (236.0, 617.0 to 617.9) were used to identify females, aged 15 to 54, with endometriosis as a diagnosis. The distribution of endometriosis admissions by admission type, length of stay (LOS), mean total charge, specific types of endometriosis, principal procedures, and other diagnosed diseases was described. RESULTS: In 1991 and 1992, 37,273 (22.6/1000) and 38,834 (23.7/1000) hospital admissions, respectively, were for endometriosis (as any diagnosis). The average LOS and total hospital charges for endometriosis as the primary diagnosis were 3.8 days and $6,597 for 1991, and 3.5 days and $7,450 for 1992. Most endometriosis admissions occurred in females aged 35 to 49. About 87% of the endometriosis hospitalizations were routine admissions. The most common diagnosis was endometriosis of the uterus (51%); the most common procedure was a total abdominal hysterectomy (55%-60%). Older and African-American patients had the longest LOS and the highest total charges. The estimated total hospitalization costs, as represented by hospital charges, for women with endometriosis as the primary diagnosis in the United States were $504 million for 1991 and $579 million for 1992. CONCLUSION: Endometriosis-related hospitalization is a major burden on healthcare systems.

Adolescent↗

Wound endometriosis: risk factor evaluation and treatment.

BACKGROUND: Wound endometriosis is still a rare phenomenon. In this study, we tried to identify its risk factors and presented our experience in managing such disease. METHODS: We studied twenty-three women with pathologically confirmed wound endometriosis after surgery between January 1990 and June 1999 retrospectively. RESULTS: Patients were classified to three groups according to the types of operations including obstetric surgery (n = 6186), gynecologic surgery (n = 3231) and laparoscopic procedures (n = 2184), which made a significant difference in the occurrence rate of endometriosis (p = 0.04): 2.7 per 1000 obstetric surgeries, 1.5 per 1000 cases of gynecologic surgeries, and 0.5 per 1000 laparoscopic procedures. Obstetric surgery showed the relative risk of occurrence of wound endometriosis 7.71 (95%: 1.03-57.92) compared with laparoscopic procedures. The median time for occurrence of wound endometriosis in patients with normal preoperative CA-125 (< 15 mIU/ml), 760 days, was significantly longer than that in patients with abnormal preoperative CA-125 (> 15 mIU/ml) of 496 days (p = 0.03). Preoperative CA-125 level, patient's age, preoperative extent of endometriosis, or operative time made no significant contributions to the occurrence of wound endometriosis. Combination therapy of surgical excision and postoperative adjuvant therapy of GnRH-agonist or Danazol showed the better prognosis because it could decrease the recurrence of wound endometriosis (42.9% versus 11%, p = 0.01). CONCLUSION: Obstetric surgery may be an important risk factor in contributing to wound endometriosis, and the aggressive behavior of endometriosis itself might also be a possible risk factor because it shortens the time of occurrence of wound endometriosis after surgery. Therapy might be dependent on individuals. Surgical excision with postoperative adjuvant therapy of either GnRH-agonist or Danazol might be valid, although its effectiveness needed proven in the future.

Adult↗

Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a case-controlled study.

OBJECTIVE: To investigate the correlation between glutathione S-transferase (GST) M1 and T1 genotypes and endometriosis risk (EM). METHODS: Polymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from the blood samples of 68 Han Chinese women with endometriosis and 28 without endometriosis. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in women with endometriosis were 0.721 (49/68) and 0.779 (53/68), respectively, and in women without endometriosis were 0.429 (12/28) and 0.321 (9/28), respectively. There was a significant difference with regard to the frequencies of GSTM1 and GSTT1 null genotypes between the women with and without endometriosis (P < 0.01). Furthermore, the frequencies of GSTM1 and GSTT1 null genotypes were significantly higher in the patients with stage III and IV endometriosis [0.731 (38/52) and 0.788 (41/52), respectively] than in women without endometriosis (P < 0.01), and the frequency of GSTT1 null genotype was statistically higher in patients with stage I and II endometriosis [0.75 (12/16)] than in the women without endometriosis (P < 0.01). No correlation between GSTM1 and GSTT1 null genotypes and age, induced abortion or dysmenorrhea was detected in this study (P > 0.05). CONCLUSION: GSTM1 and GSTT1 null genotypes may be risk factors for the development of endometriosis.

Adult↗

[Expression of vascular endothelial growth factor in the peritoneal fluid and eutopic endometrium of patients with endometriosis].

OBJECTIVE: To investigate the significance of vascular endothelial growth factor (VEGF) on the etiology of endometriosis. METHODS: The level of VEGF in the peritoneal fluid from women with endometriosis (n = 19) and non-endometriosis (n = 21) was studied by ELISA. The expression of VEGF of eutopic endometrium collected from women with endometriosis (n = 15) and non-endometriosis (n = 12) was determined by relative quantity RT-PCR. RESULTS: The level of VEGF in the peritoneal fluid in the endometriosis was higher than that of the controls (P < 0.05). Cyclic variation in VEGF concentration was seen in the peritoneal fluid from patients with endometriosis, and the VEGF concentration in the proliferative phase was significantly higher than that in the secretory phase (P < 0.05). No cyclic variation in VEGF was seen in the control group (P > 0.05). The expression of VEGF in the eutopic endometrium with endometriosis was significantly higher than that of the controls (P < 0.001). There was no significant difference between the proliferative and secretory phase in endometriosis (P > 0.05). CONCLUSION: The increase of VEGF in the peritoneal fluid and eutopic endometrium with endometriosis may be important to the occurrence and development of endometriosis.

Adult↗

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.

Analysis of Variance↗

[Incidence of endometriosis in infertile women: clinical and laparoscopic characteristics].

BACKGROUND: The incidence and symptomatology of endometriosis vary according to the different populations. OBJECTIVES: To determine the incidence of endometriosis as well as the clinical and laparoscopic characteristics in infertile women with endometriosis. PATIENTS AND METHODS: This study included 68 infertile patients with endometriosis diagnosed by laparoscopy; in all of them we analyzed the demographic and clinical characteristics. RESULTS: In 68 out of 197 medical files that were analyzed, endometriosis was reported (34.5%). The average age was 30.3 +/- 3.9 years. Forty patients had primary infertility (58.8%) and 28 (41.29%) secondary infertility. In 34 patients endometriosis (50%) was mild, moderate in 16 (23.5%) and severe in 18 (26.5%). Only one endometriosic foci was found in 25% of the patients and multiple foci in 75% of them. The most common sites in which it was found were the uterosacral ligaments, Douglas pouch and the ovaries. In patients with primary infertility it predominated the medium-high socioeconomic level and in those with secondary infertility the low one. In severe endometriosis the predominant symptom was the moderate or severe dysmenorrhea, while in mild and moderate endometriosis was mild dysmenorrhea (p < 0.007). Six out of 16 patients with severe endometriosis had endometrioma. CONCLUSIONS: The endometriosis incidence in infertile women was similar to that reported in literature, as well as age of presentation. It was also observed a direct relationship between endometriosis severity and dysmenorrhea intensity.

Adult↗

[Scoring system for screening of patients with endometriosis in infertile clinic].

An outpatient department screening method for endometriosis was prepared by designing a scoring system in a retrospective study. We compared the incidence of 21 characteristic symptoms and the finding of endometriosis in 39 infertile women with endometriosis diagnosed by laparoscopy or laparotomy and 21 women without it. A table for diagnostic scoring composed of 11 items was accomplished. The feasibility of this diagnostic scoring system was then examined in a prospective study of 72 women with endometriosis and 47 without it. The results were as follows. 1. In the retrospective study, all the women with 10 or more points had had endometriosis. Fifteen out of 20 women with -20 points or less had been without endometriosis and the remaining 5 with endometriosis (4 minimal and 1 mild stage according to AFS classification). 2. In the prospective study, a 94.5% (52/55) incidence of endometriosis was found in women with 10 or more points and 66.7% (10/15) of women with -20 points or less were without endometriosis. 3. This diagnostic scoring system, in which women with endometriosis score 10 or more points and women without it -20 points or less, has 91.2% sensitivity, 76.9% specificity, 94.5% positive predictive value and 66.7% of the negative predictive value. It is concluded that this scoring system has clinical diagnostic value in screening for endometriosis in infertile women at the outpatient department.

Adult↗

Clinical presentation and diagnosis of endometriosis.

Endometriosis is one of the most common conditions encountered in gynecology and the field of infertility. The clinical presentation depends on the location and the extent of disease, but the severity of symptoms does not correlate directly with the extent of disease. Symptoms of genital endometriosis may be categorized as menstrual dysfunction, ovulatory dysfunction, and reproductive dysfunction. With menstrual dysfunction, the frequent clinical symptoms are cyclic pelvic pain, dysmenorrhea, and dyspareunia. Endometriosis is commonly found to be the cause in younger patients with pain and dysmenorrhea, particularly when the clinician is aware of the appearance of atypical lesions. Types of ovulatory dysfunction reported to be associated with endometriosis include anovulation, premenstrual spotting, luteal phase defects, and LUF syndrome. The data are not sufficient to determine the prevalence of endometriosis, luteal phase defects, and hyperprolactinemia. With LUF syndrome, there are data to support an association, but more data on the frequency of LUF in consecutive normal cycles compared to consecutive cycles in women with endometriosis would be beneficial. A higher rate of infertility is reported in couples with endometriosis. Two approaches are used to evaluate spontaneous abortions and endometriosis. In retrospective studies, the abortion rates are higher in couples with endometriosis; however, when the pregnancy outcomes in untreated couples are studied, there is less evidence to support the association of a higher spontaneous abortion rate. Formerly, the diagnosis of endometriosis depended on the appearance of typical lesions. With the recognition of early or atypical lesions the histologic confirmation of glands and stroma is assuming a more prominent role. Noninvasive techniques such as assays of endometrial antibodies or CA-125 have certain limitations in terms of producing false-positive results and lacking predictability in early stages of disease. Ultrasonography and MRI give additional and confirmatory information. Most noninvasive techniques are ancillary in diagnosis and management. It still needs to be determined whether their routine use will give enough added information to justify their cost. Currently, the diagnosis of endometriosis is best made by histologic evidence of glands and stroma.

Antibodies↗

Detection of a unique 32-kd protein in the peritoneal fluid of women with endometriosis.

OBJECTIVE: To test the hypothesis that endometriotic tissue secretes endometriotic-specific proteins into the peritoneal fluid (PF) of women with endometriosis. DESIGN: A prospective design was utilized in this study. SETTING: Tertiary care, university-based center and reproductive endocrinology laboratory. PARTICIPANTS: Women of reproductive age who were infertile with endometriosis (n = 19), as well as without endometriosis (n = 7), and fertile women undergoing tubal ligation (n = 6). INTERVENTIONS: Collection of PF fluid via laparoscopy. MAIN OUTCOME MEASURES: Peritoneal fluid proteins were isolated and assessed by two-dimensional polyacrylamide gel electrophoresis. RESULTS: Two-dimensional electrophoresis of PF proteins isolated a group of proteins (M(r) = 32 to 40 kd, pI = 4.5 to 5.2) in all PF samples that was similar to the rat endometriotic implant-specific protein, Endo-1. This group of proteins consisted of 5 to 12 individual proteins with endometriosis PF containing a significantly higher number of proteins (median = 11) compared with either PF from infertile women without endometriosis (median = 8) or from women undergoing tubal ligation (median = 7). In addition, one protein (M(r) = 32 kd, pI = 5.8), termed EPF-32, was detected predominantly (18 of 19 samples analyzed) in PF from women with endometriosis. This protein was also detected in PF from infertile women without endometriosis (2 of 7 samples) but not in the PF of fertile women undergoing tubal ligation (0 of 6 samples). The appearance of this protein was not associated with the severity of endometriosis. CONCLUSION: It is concluded from this study that PF from women with endometriosis predominantly contains a 32-kd protein (EPF-32) compared with the PF of women without the disease. The role of EPF-32 in the pathophysiology of endometriosis is not established but this protein may function as a diagnostic marker for endometriosis.

Ascitic Fluid↗