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PubMed1996

Effect of danazol on the immunocompetent cells in the eutopic endometrium in patients with endometriosis: a multicenter cooperative study.

OBJECTIVE: To assess the effects of danazol on immunocompetent cells, human leukocyte antigen (HLA) expression, and adhesion molecules in the eutopic endometrium of patients with endometriosis. DESIGN: Antigens were localized immunohistochemically in the endometria, before treatment and during treatment (2 months later). PARTICIPANTS: Ten patients with laparoscopically proven endometriosis who consented to participate in this study were treated with 400 mg/d of danazol for 4 months. Forty-two infertile patients without endometriosis or adenomyosis served as controls. RESULTS: Immunohistochemical analysis revealed significantly increased expression of the T cell subsets, macrophages, adhesion molecules, and HLA antigens in eutopic endometrium in patients with endometriosis compared with the infertile group. Treatment with danazol reduced the number of cells in T cell subsets, adhesion molecules, or HLA antigen expression, especially of gamma delta T cells, to 39.5% of the pretreatment value in patients with endometriosis. CONCLUSIONS: Danazol had an immunomodulatory effect on the autoimmune response in endometrium associated with endometriosis.

Adult↗

PubMed1996

Antibodies to carbonic anhydrase in endometriosis: prevalence, specificity, and relationship to clinical and laboratory parameters.

OBJECTIVE: To investigate the presence and clinical association of serum autoantibodies to carbonic anhydrase (CA) in women with and without endometriosis. DESIGN: Sera were tested in an ELISA against human and bovine CAI and/or CAII isoenzymes and by Western immunoblotting of trypsin-digested fragments of human CAII as antigens. The ELISA positivity was defined as mean + 2 SD of 100 control sera. Positive sera also were tested for the presence of antiendometrial antibodies and antinuclear antibodies (ANA) by indirect immunofluorescence assays (IFA) on endometrial (ECC) and HEp-2 cells, antibodies to single-stranded (ss) and double-stranded (ds) DNA by the Farr-type RIA and Crithidia IFA, and extractable nuclear antigens (Sm, nRNP, Ro, and La) by an ELISA. PATIENTS: Sera from 319 patients with laparoscopic diagnosed pelvic endometriosis (100 stage I, 95 stage II, 67 stage III, and 57 stage IV), 100 with other gynecologic disorders, and 100 control women were used. RESULTS: In the ELISA, 113 of 319 (35.4%) endometriosis sera had elevated immunoglobulin G antibodies against nondenatured CA isoenzymes. The reactivity of sera from the endometriosis group was significantly higher (35%) in all four subgroups of patients than each of the nonendometriosis sera (< 12% and < 6%, respectively). No stage-dependent variation of an autoantibody pattern was evident. However, anti-CA autoantibodies were present in 66.3% of women with endometriosis-associated infertility. The frequency of anti-CA autoantibodies was significantly higher (by 51.7%) in women with antiendometrial antibodies detectable by IFA. In addition, in sera positive for anti-CA antibodies, the frequency of ANA also was increased (20/113 [17.6%]) with titers of 1:40 to 1:1,080. The ANA-positive sera were negative for anti-ssDNA, anti-dsDNA, anti-Sm, anti-nRNP, and anti-La. However, three sera were positive for anti-Ro antibodies. Immunoblotting study of autoantibody reactivity with trypsin-digested subfragments of human CAII revealed consistent immunoreactivity with 14 to 6.2-kd range CAII peptides. CONCLUSIONS: [1] A subgroup of patients with endometriosis have autoantibodies directed to native and linear epitopes of the CA protein. [2] Prevalence of anti-CA antibodies was associated with antiendometrial antibodies and ANA. [3] Anti-CA antibodies were associated with a higher predictive value of the disease when all patient subgroups were considered together.

Animals↗

PubMed1987

Luteal phase dysfunction in endometriosis: elevated progesterone levels in peripheral and ovarian veins during the follicular phase.

Endometriosis has been associated with corpus luteum inadequacy and abnormalities of luteal phase progesterone (P) secretion. In this study, abnormal luteolysis, as a second factor of luteal dysfunction, was assessed in 13 women with endometriosis and 25 control patients by measurement of ovarian vein estradiol (E2) and P during the follicular phase. The results reveal that women with endometriosis have (1) significantly lower ovarian vein E2, (2) significantly higher both peripheral and ovarian vein P, and (3) threefold higher P/E2 ratios than controls during the follicular phase. These data support the concept of continued P production from an active corpus luteum well into the follicular phase of the following cycle in women with endometriosis. Failure of adequate luteolysis is a second aspect of luteal dysfunction in endometriosis and strongly supports the growing body of data confirming ovulatory asynchrony in the minimal; endometriosis infertility syndrome.

Endometriosis↗

PubMed1988

Spontaneous abortions in women with endometriosis.

Pregnancy outcomes were evaluated retrospectively in 350 women to investigate the relationship between endometriosis and spontaneous abortions. The frequency of spontaneous abortions in women with endometriosis was significantly higher than in both a fertile nonendometriosis group and an infertile group with tubal disease. There was no correlation between the severity of the endometriosis and the frequency of spontaneous abortions. After treatment, the frequency of spontaneous abortions was significantly decreased in both the endometriosis and the tubal disease group, but these values were not significantly different from each other. We conclude that high spontaneous abortion rates are a characteristic of other subgroups of women with secondary infertility and not just in women with endometriosis, and that the majority of spontaneous abortions associated with endometriosis are not caused by the condition.

Abortion, Spontaneous↗

PubMed1989

Immunological aspects of surgically induced experimental endometriosis: variation in response to therapy.

Elevated endometrial antibody titers were detected in serum and peritoneal fluid of rabbits with experimentally induced endometriosis. Surgical extirpation of implants or suppression with gonadotropin-releasing hormone agonist resulted in decreased endometrial antibody titers, whereas the antibody titers in untreated rabbits with endometriosis increased significantly. Endometrial implants and normal endometrial tissue had similar proteins by polyacrylamide gel electrophoresis. However, the serum and peritoneal fluid from rabbits with experimentally induced endometriosis had gamma G immunoglobulin antibodies to an endometrial protein with molecular weight of approximately 40 kD. These antibodies were absent in rabbits without endometriosis. Isolation of endometrial antigens eliciting the humoral immune response in endometriosis may aid in the development of a specific antibody marker for endometriosis.

Animals↗

PubMed1997

Endometriosis in monozygotic twins.

OBJECTIVE: To describe the occurrence of endometriosis in monozygotic twins. DESIGN: Postal questionnaire plus confirmation of disease status. SETTING: Twins were recruited via the American Endometriosis Association and the National Endometriosis Society of Great Britain and via British gynecologists. RESULT(S): Fourteen twin pairs were concordant for endometriosis, and two were discordant. Nine pairs of twins had moderate-severe endometriosis. CONCLUSION(S): These findings contribute to the growing body of literature that suggests endometriosis has a genetic basis.

Diseases in Twins↗

PubMed1997

Distribution of heat shock proteins in eutopic and ectopic endometrium in endometriosis and adenomyosis.

OBJECTIVE: To evaluate the pathophysiologic role of heat shock proteins and to examine the effect of danazol on these proteins in patients with endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of human heat shock proteins 27, 60, and 70 in endometrial glandular cells identified using monoclonal antibodies. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Subjects were 119 women with documented endometriosis or adenomyosis. The subjects were divided into three groups: fertile control (n = 38), with 14 in the proliferative phase and 24 in the secretory phase; endometriosis (n = 38); and adenomyosis (n = 43), including 33 who underwent hysterectomy and 10 treated with danazol. MAIN OUTCOME MEASURE(S): Staining of glandular cells by semiquantitative immunostaining (evaluation nomogram) score. RESULT(S): Significantly increased expression of heat shock protein 27 was noted in eutopic endometrium from patients with endometriosis and adenomyosis as compared with controls, regardless of the menstrual phase. The scores for heat shock protein 27 and heat shock protein 70 in the ectopic endometrium of patients with endometriosis were low compared with those in eutopic endometrium, whereas in adenomyosis, the scores were similar to those of eutopic endometrium. After treatment with danazol, the expression of heat shock proteins returned to control levels. CONCLUSION(S): We suggest that abnormally increased expression of heat shock proteins plays a role in the pathophysiology of endometriosis and adenomyosis.

Adult↗

PubMed1997

In vitro culture of endometrial stromal and gland cells as a model for endometriosis: the effect of peritoneal fluid on proliferation.

OBJECTIVE: To test the hypothesis that the cell-free fraction of PF from women with endometriosis affects the proliferation of endometrial epithelial and stromal cells in vitro. DESIGN: A cell biologic and immunohistochemical study. SETTING: University teaching hospital. PATIENT(S): Premenopausal women undergoing laparoscopy and women with histologically normal endometrium undergoing hysterectomy were selected. INTERVENTION(S): Peritoneal fluid (PF) and serum were collected at laparoscopy. Endometrial epithelial and stromal cells were obtained by enzymic dissociation of tissue, and epithelium was separated from stromal cells by sieving. Epithelial and stromal cell populations were purified by removal of contaminating cells using Thy-1-and CD-45-labeled immunomagnetic beads. Isolated endometrial gland and stromal cells were cultured in the presence of PF or serum from women with and without endometriosis. MAIN OUTCOME MEASURE(S): Cell proliferation was assessed by measurement of incorporation of 3[H]thymidine after 48 hours in culture. RESULT(S): Isolated endometrial gland and stromal cells were able to proliferate in vitro. The proliferative effect of PF or sera from women with endometriosis did not differ significantly from normal controls. CONCLUSION(S): We conclude that PF from women with endometriosis does not have an additional mitogenic effect compared with women without endometriosis. It may be postulated that the endometrium from women with endometriosis responds differently to the effects of PF.

Adult↗

PubMed1998

Ovarian fecundity in patients with endometriosis can be estimated by the incidence of apoptotic bodies.

OBJECTIVE: To investigate the incidence of apoptotic bodies in membrana granulosa in patients with endometriosis. DESIGN: Retrospective analysis. SETTING: Yamagata University Hospital. PATIENT(S): Fifty-eight normoovulatory women with endometriosis and 45 patients with male factor infertility underwent ovulation induction for IVF-ET with GnRH analogues and gonadotropins. INTERVENTION(S): Patients underwent follicle aspiration after the administration of hCG. MAIN OUTCOME MEASURE(S): Recovered granulosa cells (GCs) were examined by fluorescence microscopy, and the incidence of apoptotic bodies was tabulated. These data and the other parameters associated with IVF results were analyzed on the basis of both the revised American Fertility Society (AFS) classification of endometriosis and the existence of chocolate cysts. RESULT(S): The incidence of apoptotic bodies in membrana granulosa of patients with endometriosis was significantly higher than that of the control (male factor infertility) group and increased as the stage of the revised AFS classification advanced. The incidence of apoptotic bodies in membrana granulosa was significantly higher in patients with chocolate cysts than in those without chocolate cysts. The patients with endometriosis had smaller numbers of developed follicles (> or = 15 mm), harvested oocytes, and mature oocytes than the male factor infertility patients. The existence of chocolate cysts corresponded with a reduced number of both harvested oocytes and mature oocytes. CONCLUSION(S): Through the apoptosis of GCs, the existence of endometriosis may have negatively affected the follicle development and oocyte quality.

Adult↗

PubMed1998

Laparoscopic surgical management of diaphragmatic endometriosis.

OBJECTIVE: To review the clinical presentations of and management options for diaphragmatic endometriosis. DESIGN: Retrospective review. SETTING: Referral center. PATIENT(S): Twenty-four women with endometriosis of the diaphragm. INTERVENTION(S): Surgical management. MAIN OUTCOME MEASURE(S): Diagnostic accuracy and therapeutic feasibility of operative laparoscopy. RESULT(S): Operative findings in 17 patients included 2-5 spots of endometriosis on the diaphragm measuring <1 cm. Seven women had numerous lesions scattered across the diaphragm. Lesions were bilateral in 8 patients, limited to the right hemidiaphragm in 14 patients, and limited to the left hemidiaphragm in 2 patients. In 7 patients, six endometriosis lesions were directly in the line of the left ventricle and three lesions were adjacent to the phrenic nerve. Endometriosis was infiltrating into the muscular layer of the diaphragm in 7 patients. The symptoms in all 7 symptomatic patients decreased significantly after treatment, with a minimum follow-up period of 12 months. No postoperative complications occurred. CONCLUSION(S): The abdominal diaphragm can be involved with endometriosis and can be diagnosed and treated effectively with the use of videolaparoscopy.

Adolescent↗

PubMed1998

Tissue inhibitor of metalloproteinase-1 concentrations are attenuated in peritoneal fluid and sera of women with endometriosis and restored in sera by gonadotropin-releasing hormone agonist therapy.

OBJECTIVE: To establish tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in peritoneal fluid (PF) and sera of women with endometriosis and compare them to disease-free controls. DESIGN: Prospective randomized study. SETTING: Academic medical center. PATIENT(S): Women with laparoscopically documented endometriosis and disease-free women of reproductive age. INTERVENTION(S): Peritoneal fluid and sera were collected, and some women received gonadotropin-releasing hormone agonist (GnRH-a) therapy for endometriosis. MAIN OUTCOME MEASURE(S): Peritoneal fluid and sera TIMP-1 concentrations were measured with a specific RIA. RESULT(S): The TIMP-1 concentrations were significantly lower in PF and sera of women with endometriosis compared with disease-free women. The GnRH-a therapy restored serum TIMP-1 concentrations. CONCLUSION(S): Aberrant expression and localization of TIMP-1 may derange the proteolytic milieu of the peritoneal cavity and contribute to the etiology and underlying physiologic sequelae associated with endometriosis. Measurement of TIMP-1 in serum may aid in diagnosing endometriosis and assist with monitoring treatment efficacy in women with this disease.

Administration, Inhalation↗

PubMed1998

Evidence for oxidatively modified lipid-protein complexes in endometrium and endometriosis.

OBJECTIVE: To evaluate for the presence of oxidatively modified lipid-protein complexes in endometriosis and endometrium of women with endometriosis and controls. DESIGN: Controlled clinical study. SETTING: Academic tertiary care center. PATIENT(S): Women undergoing surgery for pelvic pain, infertility, endometriosis, or tubal ligation controls. INTERVENTION(S): Biopsy of endometrium and endometriosis. MAIN OUTCOME MEASURE(S): Staining with antibodies to oxidatively modified lipid proteins (HNE-7, MDA2), macrophages (HAM-56), and muscle cell actin (HHF-35). RESULT(S): Both endometrium and endometriosis tissues contain stromal cells that immunostain with HAM-56 and show immunostaining (both intracellular and extracellular) with HNE-7 and MDA2. Some endometriotic implants show patchy staining with HHF-35. Endometrium was devoid of staining with HHF-35. Control staining with nonimmune sera in both tissues was also devoid of staining. CONCLUSION(S): These data strongly implicate the occurrence of oxidative stress in endometriosis tissue. These data also suggest that oxidative modification is a normal physiological process in endometrium.

Adult↗

PubMed1999

Genetic influences on endometriosis in an Australian twin sample. sueT@qimr.edu.au.

OBJECTIVE: To investigate the prevalence of and twin pair concordance for endometriosis. DESIGN: A questionnaire survey incorporating validation. SETTING: An Australia-wide volunteer sample of female monozygotic (MZ) and dizygotic (DZ) twin pairs from the Australian National Health and Medical Research Council Twin Register. PATIENT(S): Twins were selected only on the basis of previous participation in twin research. INTERVENTION(S): Questionnaires were sent to 3,298 individuals. Information was requested from physicians named by consenting twins. MAIN OUTCOME MEASURE(S): Reported endometriosis, validated where possible by pathology or surgical report. RESULT(S): Three thousand ninety-six (94%) of the twins and 145 (82%) of the physicians responded to the survey. Two hundred fifteen twins reported endometriosis, for a prevalence rate of .07 among question respondents. Tetrachoric twin pair correlations for self-reported endometriosis (MZ: n = 854 and DZ: n = 493) were rMz = .46+/-.09 and rDz = .28 +/-.13. When available medical and pathology reports were included, they changed to rMz =.52 +/-.08 and rDZ = .19+/-.16, suggesting that 51% of the variance of the latent liability to endometriosis may be attributable to additive genetic influences. CONCLUSION(S): These findings support the hypothesis that genes influence liability to endometriosis.

Adolescent↗

PubMed1999

Expression of secretory leukocyte protease inhibitor in women with endometriosis.

OBJECTIVE: To explore endometriosis-related molecules in patients with use of differential display analysis. DESIGN: Prospective study. SETTING: Nagoya City University Medical School, Nagoya, Japan. PATIENT(S): Women with endometriosis (n = 27) and without endometriosis (n = 21). INTERVENTION(S): Surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Differentially expressed products of endometrioma samples were sequenced at nucleotides. One of the candidate genes, secretory leukocyte protease inhibitor (SLPI) gene, was analyzed with use of in situ hybridization and Northern blot analyses. Distribution of SLPI was determined by immunohistochemistry, and the amount of SLPI in the peritoneal fluid and serum was measured by ELISA. RESULT(S): Distinct expression of SLPI messenger RNA could be detected in the endometrial-type epithelium of extrauterine endometriotic tissues and in the eutopic endometrium of women with endometriosis. SLPI was localized in the endometrial-type epithelium of endometriomas immunohistochemically. The amount of SLPI in the peritoneal fluid was markedly elevated in the endometriosis group (91.6+/-6.6 ng/mL compared with 68.4+/-5.3 ng/mL in the controls). CONCLUSION(S): Secretory leukocyte protease inhibitor may be involved in the pathogenesis of endometriosis.

Adult↗

PubMed2000

Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To determine whether folliculogenesis is impaired in patients with endometriosis. DESIGN: Prospective study. SETTING: Yamagata University School of Medicine, Yamagata, Japan. PATIENT(S): Thirty women participating in an IVF program. INTERVENTION(S): The patients were divided into four groups according to the cause of their infertility: tubal factor (T), n = 7; male factor (M), n = 7; idiopathic (I), n = 7; and endometriosis (E), n = 9. Granulosa cells were obtained from the follicular fluid of each patient and analyzed by flow cytometry. MAIN OUTCOME MEASURE(S): The percentage of granulosa cells in each cell-cycle stage. RESULT(S): The mean (+/- SD) rate of apoptosis in the granulosa cells obtained from the patients with endometriosis was the highest among the four groups (T = 11.7% +/- 3.3%; M = 5.6% +/- 3.8%; I = 9.6% +/- 5.1%; and E = 18.6% +/- 9.6%). The percentage of S-phase granulosa cells was significantly higher in the patients with endometriosis than in all the other patients combined (E = 12.5% +/- 6%; T + M + I = 9.3% +/- 2.9%). The percentage of G2/M-phase granulosa cells was significantly lower in the endometriosis group than in the other three groups combined (E = 2.3% +/- 2.5%; T + M + I = 4.6% +/- 2.1%). CONCLUSION(S): Endometriosis impairs the cell cycle in granulosa cells. This phenomenon may have a detrimental effect on folliculogenesis.

Adult↗

PubMed2003

Histological classification of endometriosis as a predictor of response to treatment.

OBJECTIVES: To evaluate the usefulness of the histological classification of endometriosis in predicting responses to treatment. METHODS: We evaluated 412 biopsy specimens from 241 patients with pelvic endometriosis. Pain and infertility were evaluated before surgery. Disease location and stage of development were analyzed according to the 1985 American Society of Reproductive Medicine (ASRM) classification. Histological findings were classified as stromal, well-differentiated, undifferentiated, and mixed endometriosis. Clinical response to pain or infertility was evaluated. RESULTS: Histological findings, disease location and stage of development, and response to treatment were compared. Undifferentiated endometriosis was more frequently associated with stages III/IV than the well-differentiated and stromal histological types. Pure or mixed undifferentiated patterns were more frequently associated with rectovaginal endometriosis. When considering pain symptoms, patients presenting well-differentiated or stromal histological patterns responded better to therapeutic treatment than those who presented undifferentiated histological patterns. There were no significant differences in cases related to sterility. CONCLUSIONS: The histological categorization of endometriosis can help predict the behavioral patterns of the disease.

Adolescent↗

PubMed2000

Bladder endometriosis: conservative management.

PURPOSE: We evaluate the characteristics of women with bladder endometriosis successfully treated with hormonal therapy. MATERIALS AND METHODS: The records of 14 patients with a mean age of 48.7 years (range 26 to 71) diagnosed with bladder endometriosis on cystoscopic evaluation were reviewed for presenting complaints, findings and response to therapy. RESULTS: The most frequent presenting complaints were urgency (78%), frequency (71%), suprapubic pain (43%), urge incontinence (21%) and dyspareunia (21%). Of the patients 86% did not have a history of recurrent urinary tract infections, 6 (42%) had a history of endometriosis, including 3 who were previously treated with hysterectomy/oophorectomy and 8 (57%) were on some form of therapy for estrogen deficiency. In all patients endometrial implants were identified on cystoscopic examination. In 2 patients the endometrioma correlated to lesions on the serosal surface of the bladder during laparoscopic evaluation. Of the patients 13 were treated either with low dose oral contraceptives, decrease or elimination of the estrogen component of the present regimen or addition of progesterone to therapy, and 12 (92%) reported sustained improvement of symptoms at a mean of 18.6 months (range 8 to 24). CONCLUSIONS: In more than 70% of cases the presenting symptoms of bladder endometriosis are identical to those of interstitial cystitis. Therefore, endometriosis should always be considered in the patient referred for frequency, urgency and pain with no documented infection. Hormonal therapy is reasonable and effective management for bladder endometriosis. This option preserves fertility, making it especially attractive to younger women.

Adult↗

PubMed2000

A randomized comparison of danazol and leuprolide acetate suppression of serum-soluble CD23 levels in endometriosis.

OBJECTIVE: To determine the effects of treatment with danazol and leuprolide acetate depot on serum-soluble CD23 concentrations in women with endometriosis. METHODS: This randomized trial involved 20 women 18-42 years old with regular menses and known pelvic endometriosis who were recruited from a university hospital between 1993 and 1998. Ten women took 200 mg of danazol three times daily for 6 months, and the remaining ten were given 3.75 mg of leuprolide acetate depot every 28 days for 6 months. Blood-soluble CD23 levels were measured before treatment, during the last 15 days of the 6-month treatment course, and 3 months after treatment. Only one blood sample was taken from ten women without endometriosis, between the 5th and 7th days of their menstrual cycles. For statistical analysis, we used independent and paired t tests with the Pearson correlation coefficient. RESULTS: Soluble CD23 levels were significantly higher in women with endometriosis before treatment than in ten normal controls. Levels decreased significantly during treatment with either danazol or leuprolide acetate. Three months after treatment, soluble CD23 values remained lower than before treatment. There was no correlation between soluble CD23 concentrations and severity of endometriosis. CONCLUSION: Our findings suggest that endometriosis increases soluble CD23 levels, which can be suppressed with either danazol or leuprolide acetate injection.

Adolescent↗