The new application of mifepristone in the relief of adenomyosis-caused dysmenorrhea

Int J Med Sci. 2020 Jan 14;17(2):224-233. doi: 10.7150/ijms.39252. eCollection 2020.

Abstract

Background: Adenomyosis is a quite common gynecological disorder and above 30% of patients have typical secondary and progressive dysmenorrhea. Current treatments still have many disadvantages and thereby the novel treatment aiming to relieve dysmenorrhea still needs to be further investigated. Mifepristone is a wonderful drug because it is effective, safe and cheap in many diseases including adenomyosis. In this study, we aim to investigate if mifepristone could be used in the treatment of adenomyosis-associated dysmenorrhea. Methods: Human primary endometrial epithelial and stromal cells from adenomyosis patients were isolated and treated with mifepristone. RNA-sequencing was then performed to detect the gene changes of pain-related inflammatory mediators. Meanwhile, the effect of mifepristone on the infiltration and degranulation of mast cells were investigated in adenomyosis lesions. Additionally, the role of mifepristone on the density of nerve fibers was also studied in the ectopic endometrium. At last, to evaluate the therapeutic efficacy of mifepristone on dysmenorrhea of adenomyosis, twenty participants were included and the visual analog scale (VAS) score was assessed and compared before and after treatment with mifepristone. Results: We demonstrated that mifepristone reduced the secretion of IL-6 and TNF-α from endometrial epithelial and stromal cells, restricted the infiltration and degranulation of mast cells in eutopic and ectopic endometrium and decreased the density of nerve fibers by inhibiting the migration capacity of nerve cells in adenomyosis. Meanwhile, we found that mifepristone could significantly relieve dysmenorrhea of adenomyosis. Conclusion: The findings demonstrated that mifepristone could be applied in the treatment of dysmenorrhea for the adenomyosis patients.

Keywords: adenomyosis; dysmenorrhea; inflammation; mast cell; mifepristone; nerve fiber.

MeSH terms

  • Adenomyosis / complications*
  • Cell Line
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dysmenorrhea / drug therapy*
  • Dysmenorrhea / etiology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Mast Cells / drug effects
  • Mast Cells / metabolism
  • Mifepristone / therapeutic use*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Mifepristone