简介：AbstractObjective:To study the 12-month effects and possible mechanisms of low-dose mifepristone in the treatment of adenomyosis.Methods:Patients included in this retrospective study had painful adenomyosis and previously received 5 mg mifepristone daily (group A, n = 45) or 5 mg mifepristone daily with a poor-effect levonorgestrel-releasing intrauterine device (group B, n = 13) for 12 months. Uterine size, serum CA125 levels, estradiol levels, Visual Analogue Scale (VAS) score, endometrial thickness, and hemoglobin levels were compared before and after treatment and investigated again at 3 to 6 months after drug withdrawal. Another 8 patients with adenomyosis (group C, n = 8) who underwent surgery for severe dysmenorrhea during the same period were only used as a control group for immunohistochemical research. Endometrial biopsy results and expression of nerve growth factor (NGF), cyclooxygenase-2 (COX-2), and nuclear-associated antigen Ki-67 (Ki-67) in endometrial tissues and adenomyotic lesions were also analyzed.Results:The VAS scores in both experimental groups at all time points during treatment and follow-up were significantly lower (P <0.001) than those before treatment. The uterine size was significantly reduced, and endometrial thickness was distinctly thicker after 12 months of treatment than that before treatment in group A receiving 5 mg/d mifepristone. The immunohistochemical expression of NGF and COX-2 decreased in both eutopic and ectopic endometrium after treatment, whereas that of Ki-67 slightly increased in eutopic endometrium after treatment and rapidly recovered to the baseline value after stopping mifepristone. There were no signs of hyperplasia, atypical hyperplasia, or malignancy in the endometrial biopsies.Conclusions:The results suggested that a daily dose of 5 mg mifepristone for 12 months down-regulated the expression of NGF and COX-2 and was effective in treating painful adenomyosis with few side effects.

简介：AbstractObjective:Despite the fact that adenomyosis is a fairly common gynecological disorder, its pathogenesis remains elusive. Several theories on the pathogenesis of adenomyosis have been proposed, but none of them has been proven experimentally. So far, the most used one is the neonatal feeding of tamoxifen (TAM) in Institute of Cancer Research/cryopreserved (ICR/CD-1) mouse. However, its underlying mechanism of action is unknown. To further delineate the mechanism of TAM-induced adenomyosis in ICR/CD-1 mouse with regard to specific estrogen receptor (ER), we conducted an experiment that neonatal mice were fed with either TAM, or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT; an ERα agonist), or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; an ERβ agonist), or G-1 (a G-protein coupled receptor 30 agonist), or just vehicle, in an attempt to tease out which specific receptor plays a dominant role in the genesis of adenomyosis induced by neonatal feeding of TAM.Methods:Forty female neonatal mice were randomly divided into 5 equal-sized groups: CTL (control), TAM, PPT, DPN, and G-1. Three months later, all mice were sacrificed and their uterine horns were harvested, weighed, and processed for histological evaluation.Results:All mice in the TAM group developed adenomyosis, so did 4 mice (50%) in the DPN group, a result that should be considered significant given that mice in the CTL group would not develop adenomyosis. No mouse in the PPT or G-1 group developed adenomyosis. Remarkably, all lesions in the DPN group were seen exclusively near the uterine serosa, which are dramatically different from that of TAM mice and reminiscent of extrinsic or external adenomyosis in humans.Conclusions:Neonatal feeding of DPN induces adenomyosis, but the adenomyotic lesions appear to be different from those induced by TAM. Thus, the cause of TAM-induced adenomyosis in ICR/CD-1 mouse cannot be attributable to one specific ER alone. This suggests that the extrinsic/external adenomyosis may have a pathogenesis that is different from other sub-types of adenomyosis.