Mifepristone Treats Symptomatic Adenomyosis: A Multicentre, Randomized, Double-Blind and Placebo-Controlled Trial

Background: Despite advancements in drug therapy, many patients with adenomyosis fail to achieve treatment goals. Therefore, new therapies need to be developed. Our aim was to evaluate the efficacy, safety and tolerability of mifepristone versus placebo in the treatment of painful adenomyosis. Methods: We conducted a randomized, multicenter, double-blind and placebo-controlled trial in 10 hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio to receive mifepristone or placebo orally once a day for 12 weeks. The randomization sequence was generated by the block-rank package of R software with a block size of four. Randomization was performed centrally with an interactive web response system. Regular trial visits were performed every 4 weeks and lasted to 4 weeks after treatment. Patients, investigators, clinicians and statisticians were masked to the treatment allocation throughout the study. The primary outcome was the change in adenomyosis-associated dysmenorrhea intensity evaluated by visual analog scale (VAS) in intention-to-treat population. Secondary outcomes were the changes in menstrual blood loss, the levels of hemoglobin and CA125, platelet count and uterine volume after 12-week treatment. Safety analyses were done in patients with at least one dose of the product intervention. This trial is registered with ClinicalTrials.gov, NCT03520439. Findings: Between May 2018 and April 2019, 134 adenomyosis patients with dysmenorrhea were randomly assigned. Eight patients without any valid data at baseline were excluded and 126 patients were included in efficacy analysis (61 to mifepristone and 65 to placebo). The mean changes in VAS score were −6.63 (standard deviation [SD] 1.92) in mifepristone group and −0.95 (SD 1.75) in placebo group (p < 0.0001). The total effective and complete remission rates for dysmenorrhea in mifepristone group were significantly higher than those in placebo group ( 91.80% vs. 23.08% and 88.52% vs. 6.15%, respectively ). All the secondary outcomes showed significant improvements after mifepristone treatment for menstrual blood loss, the levels of hemoglobin and CA125, platelet count and uterine volume (P < 0.0001 for all). Safety analysis revealed no significant difference between two groups, and no serious adverse events were reported. Interpretation: Treatment with mifepristone resulted in significantly lower pain scores for adenomyosis patients with dysmenorrhea . Secondary outcomes were all met with a significant improvement with no new safety concerns and well-toleration. These data support that mifepristone could serve as a new treatment option for adenomyosis patients to relieve the symptoms with safety. Trial Registration: This trial is registered with ClinicalTrials.gov, NCT03520439. Funding/Support: This study was supported by National Key R&D Program of China (Grant number: 2017YFC1001202), National Natural Science Foundation of China (Grant numbers: 81974225, 81671429 and 81802591), Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation (Grant number: 19331203) and Jiaxing Municipal Public Welfare Research Project (Grant number: 2021AY30004). Declaration of Interest: None to declare. Ethical Approval: Ethical approval was obtained by the institutional review board or ethics committee at each investigational site before the initiation of the trial.