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CONTEXT - Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis.
OBJECTIVE - The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model.
METHODS - Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg x d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells.
PRIMARY OUTCOME - The number and size of endometriotic implants were measured.
RESULTS - Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1alpha).
CONCLUSIONS - Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins.
Sonohysterography is a simple ultrasound (US) procedure that may be used to evaluate the endometrium. The technique involves placement of a 5-F catheter into the endometrial canal with subsequent instillation of sterile saline solution under US guidance. Fifty patients successfully underwent sonohysterography because of apparent abnormal endometrial thickening at transvaginal US, a nonspecific finding. Patients tolerated this procedure well, and no complications were encountered. In the 39 patients who proved to have endometrial pathologic conditions, sonohysterography demonstrated focal processes (polyps, carcinoma, hamartoma) in 15, diffuse processes (hyperplasia, secretory endometrium) in 21, and both focal and diffuse pathologic conditions in three. If a focal process can be delineated, a visually directed biopsy may be necessary. However, if the process is diffuse, a blind aspiration biopsy may be performed on an outpatient basis. In the majority of patients, the diffuse or focal nature of the disease could not be predicted on the basis of initial transvaginal US. Because sonohysterography allows distinction between diffuse and focal abnormalities, it provides physicians with a cost-effective way to plan the next step in case management.
Transrectal sonography was used to provide intraoperative guidance for dilatation and curettage and placement of intrauterine tandem apparatus in 20 patients in whom the external cervical os could not be visualized adequately. Transrectal sonography was found to be useful in providing guidance for these procedures and at the same time helped avoid uterine perforation. This method also was used during cerclage placement in two patients who had undergone several conizations. Transperineal sonography was used in three patients whose area of abnormality was best approached transperineally. These cases included transvaginal biopsy of a metastatic trophoblastic tumor and one guided aspiration of a perirectal abscess after pelvic exenteration. The potential advantages and pitfalls in the intraoperative use of transrectal and transperineal sonography for guided intrauterine procedures are discussed and illustrated.