A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis

Abstract

Adenomyosis is also called internal endometriosis and affects about 20% of reproductive‐aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long‐term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side‐effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria‐dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial‐mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick.

Decreased Indian hedgehog signaling activates autophagy in endometriosis and adenomyosis

“…The medium was then discarded, and the cells were gently washed with PBS to remove blood cells and debris. The purity of EuESCs in our experiment was >95%, as determined by positive immunostaining for vimentin and negative staining for cytokeratins-19 (Choi et al 2015, Che et al 2020. Second and third passages of cells were used for subsequent experiments.…”

“…However, they also share many similarities, including estrogen dependency, progesterone resistance, and multiple cellular and molecular aberrations (Vannuccini et al 2017, Kobayashi et al 2020, Zhu et al 2016. For many years, adenomyosis was considered a specific form of endometriosis called endometriosis interna (Vannuccini et al 2017, Che et al 2020. Although endometriosis and adenomyosis cause severe symptoms in patients, they are generally believed to be chronic benign uterine diseases.…”

“…Although endometriosis and adenomyosis cause severe symptoms in patients, they are generally believed to be chronic benign uterine diseases. However, ectopic endometrial cells also have certain malignant biological behaviors, such as aggressive invasion, migration, unrestrained proliferation, and reduced susceptibility to apoptosis (Liu et al 2017, 2019b, Che et al 2020). These features are important for the pathogenesis of endometriosis and adenomyosis.…”

Clinical Utility of Mifepristone: Apprising the Expanding Horizons

“…It restricts the migration of endometrial and stromal cells in adenomyosis. Therefore mifepristone can effectively inhibit the emergence and development of adenomyosis, decrease the uterine volume and cancer antigen-125 (CA-125) concentration, and increases the hemoglobin concentration in serum for adenomyosis patients [58,59]. In an interventional study of 20 adenomyosis patients on mifepristone 5 mg/day, there was significant relief concerning dysmenorrhea.…”

Clinical Update on Uses for Mifepristone in Obstetrics and Gynecology

“…The authors found that mifepristone inhibited the cells' migratory capacity, inhibited their epithelial-mesenchymal transition, and induced apoptosis. From a clinical perspective, patients treated with mifepristone had a statistically significant decrease in uterine volume and statistically significant increase in hemoglobin in the 3 months on treatment prior to hysterectomy 80 …”