Increased leptin levels in serum and peritoneal fluid of patients with pelvic endometriosis.

Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by ectopic implants of endometrium in the peritoneal cavity and associated with increased secretion of proinflammatory cytokines and neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a role in food intake, basal metabolism, and reproductive function. Leptin levels are dynamically regulated, being elevated by inflammatory mediators and reduced by starvation. Leptin itself can influence the proinflammatory immune responses of CD4+ T lymphocytes, and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo. We investigated whether leptin concentrations in serum and peritoneal fluid (PF) differed between 13 patients with different stages of endometriosis and 15 age- and body mass index-matched controls. We found a statistically significant (P < 0.05) increase in leptin levels in serum (30.3 +/- 14.8 ng/mL) and PF (35.9 +/- 17.4 ng/mL) of patients with endometriosis, compared with our control population (serum, 15.6 +/- 8.4; PF, 17.5 +/- 7.2 ng/mL). Regression equations, relating leptin to body mass index, were also significantly different in endometriosis patients, compared with controls. Higher levels of leptin were observed in the earlier stages of endometriosis than advanced-stage disease. These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis.

Reproductive outcome after hysteroscopic metroplasty.

OBJECTIVE: To evaluate the reproductive outcome after hysteroscopic metroplasty. STUDY DESIGN: We analysed the reproductive outcome of 69 patients, with different degrees of septate uterus, undergoing hysteroscopic metroplasty in the outpatient infertility clinic of Naples 'Federico II' University. Of the 69 patients, 48 had a history of recurrent abortion while 21 had a primary infertility. In all cases the procedure was performed by means of the resectoscope. RESULTS: In 97.1% of the cases post-operative hysterosalpingogram or hysteroscopic examination showed a normal cavity with a little fundal notch. In two cases, second surgery was needed. Of the 48 patients affected by repeated abortion, 40 became pregnant after the metroplasty whereas, to date, in the infertile group only six out 21 (29.0%) conceived. We observed a total of 46 pregnancies with two sets of twins. Of these, 31 pregnancies (67.4%) were carried to term, five (10.8%) ended in preterm delivery, six (13%) ended in spontaneous abortion and four (8.6%) are in progress. Cervical cerclage was performed on 13 women. Only one (7.6%) woman with cervical cerclage had a preterm delivery, while the preterm delivery rate in women without cerclage was 12.1%. The modality of term pregnancy deliveries was cesarean section in 48% of the cases and vaginal delivery in the 52%. CONCLUSIONS: Our data analysis suggest that the correction of mullerian anomalies does not improve the pregnancy rate, but only the pregnancy outcome of the patients.

[Effects of danazol on the endometrium during peri-menopausal meno-metrorrhagia]. / Effetti del danazolo sull'endometrio nella menometrorragia perimenopausale.

Perimenopausal abnormal bleeding is one of the most common gynecological problems. We have assessed the effectiveness of danazol 200 mg daily for 3 months in 42 patients with perimenopausal abnormal bleeding without any previous treatment and in 23 patients previously treated with norethisterone or medroxyprogesterone acetate but with a recurrence of bleeding 2 months after the end of the treatment. In the overall population treated by danazol at the end of treatment we had: bleeding normalized in 88.2% and hysteroscopic patterns, showing regression of hyperplasia in 95% of cases. The endometrial effects were maintained 2 months after the end of treatment with an increase of the hyperplastic pictures at 4 (26%) and up to 12 months (60%). We had amenorrhea in 10% of patients at the end of treatment and in 2 cases only treatment was discontinued for severe side effects. The comparison of these better results with those obtained by progesterone agents and with those of a preliminary experience with GnRH agonists had led us to consider the importance of an additional endometrial effects exerted by danazol. Particularly the immunosuppressive properties of this drug, as we have shown in "in vitro" conditions, can determine a decreased secretion of growth factors by local immune cells which in turn can further explain the endometrial antiproliferative action of this drug.

Immune system and endometriosis.

Many experimental and clinical findings indicate a disimmune pathogenesis of infertility associated with endometriosis. The most important modifications of cell-mediated immunity in endometriosis concern macrophage activity, increased both quantitatively and qualitatively. Peritoneal macrophages (PM) acquire the ability of producing lytic enzymes, that would be able to enhancing and stimulating implantation and proliferation of endometrial cells in peritoneal cavity. In these last years many experimental and clinical demonstrations have showed an immunosuppressive action of Danazol similar to corticosteroids. The Authors report their study on a comparison among Danazol 600 mg/daily for 3 months plus a local immunosuppressive treatment combined with superovulation and IPI, Danazol for 3 months plus superovulation and IPI and, as a control group, superovulation and IPI.

Serum concentrations of soluble human leukocyte class I antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions.

Serum concentrations of soluble human leukocyte class I antigens (sHLA-I) and of the intercellular adhesion molecule-1 (sICAM-1) are increased in the early inflammatory stages of several immune-related diseases. These soluble molecules also exert immunomodulatory activity, including regulation of natural killer (NK) cell cytotoxicity. The aim of this study was to verify whether sHLA-I and sICAM-1 serum concentrations are related to the various stages of pelvic endometriosis, which is an immune-related disorder associated with impaired in-vitro NK cell activity. Serum sHLA-I and sICAM-1 concentrations were similar in patients and in healthy donors. However, when evaluated according to disease stage, sHLA-I and sICAM-1 concentrations were higher in patients with endometriosis stage I-II (revised American Fertility Society classification), or with non-pigmented peritoneal lesions. In conclusion, studies on sHLA-I and sICAM-1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome.

The peritoneal fluid concentration of leptin is increased in women with peritoneal but not ovarian endometriosis.

This study was designed to measure leptin concentrations in the peritoneal fluid (PF) of women with different aspects of pelvic endometriosis. Among 36 consecutive women undergoing laparoscopy, nine were diagnosed as having minimal-mild endometriosis (stage I-II). Among nine other subjects with advanced stage (III-IV) disease, six showed one or more ovarian endometriotic cysts as the only operative finding. The remaining 18 unaffected women constituted the control group. Patients with endometriosis had significantly higher PF leptin concentrations (32.6 +/- 16.2 versus 17.1 +/- 6.6 ng/ml, P = 0.002); this difference remained significant when corrected for body mass index (BMI) (PF leptin/BMI ratio 1.41 +/- 0.67 versus 0.76 +/- 0.28, P = 0.001). Furthermore, the PF leptin/BMI ratio was significantly higher in women with peritoneal implants than in those in whom no implant was found at laparoscopy (1.6 +/- 0.7 versus 0.83 +/- 0.33, P = 0.007). Conversely, patients with one or more ovarian endometriomata as the only finding, had a PF leptin/BMI ratio comparable with that in women where no cyst was found (1.05 +/- 0.4 versus 1.1 +/- 0.65). In women with stage I-II endometriosis, a higher mean PF leptin/BMI ratio was found compared with those affected by stage III-IV (1.78 +/- 0.68 versus 1.05 +/- 0.43, P = 0.01). These results show that during endometriosis the presence of peritoneal disease, and not of ovarian endometriotic cysts, influences leptin concentrations in PF. The data suggest that leptin may play a role in the development of peritoneal endometriosis, and that different biochemical phenomena might be involved in the pathogenesis of the ovarian form of the disease.