麻豆传媒

Treatment with a low daily dose of mifepristone (Mifeprex), a drug used in medication abortions, was effective and safe for women with adenomyosis, a painful and chronic gynecologic condition, a randomized trial from China showed.

After 12 weeks of treatment, the mean change in adenomyosis-associated dysmenorrhea intensity, as measured by a visual analog scale (VAS) was -6.63 in patients who received mifepristone (10 mg) compared with -0.95 among patients who received placebo (P<0.001), reported Xinmei Zhang, PhD, of Zhejiang University in Hangzhou, and co-authors.

The effective remission rate of dysmenorrhea was 91.8% among the 61 patients in the mifepristone group versus 23.1% among the 65 patients in the placebo group, and the complete remission rates were 88.5% versus 6.2%, they noted in .

Zhang and team said that treatment options for adenomyosis -- a condition in which endometrial tissue exists within and grows into the uterine wall, also known as "internal endometriosis" -- are limited, with many patients opting to undergo a hysterectomy to treat pain symptoms.

Approximately 20% of reproductive-age women are diagnosed with adenomyosis, according to the authors. The disease can lead to serious health problems, such as progressive dysmenorrhea, menorrhagia, secondary anemia, an enlarged uterus, subfertility, miscarriage, and obstetric complications.

"Unfortunately, there are no approved medical guidelines for adenomyosis. Medical treatment for adenomyosis, including gonadotropin-releasing hormone agonist (GnRH-a), oral contraceptives, and progestins, are limited in terms of effectiveness, tolerability, and costs," they wrote. "The current medical treatment strategy for adenomyosis is an unmet medical need."

In the study, all secondary endpoints also showed significant improvements in mean changes from baseline following mifepristone treatment compared with placebo (all (P<0.001):

• Hemoglobin: 2.13 g/dL vs 0.48 g/dL
• CA125 levels: -62.23 U/mL vs 26.89 U/mL
• Platelet count: -28.87×10³/μL vs 2.06 ×10³/μL
• Uterine volume: -29.32 cm³ vs 18.39 cm³

Mild to moderate adverse events were reported in 30.5% of the mifepristone group and 21.9% of the placebo group, and no serious adverse events were reported in either group.

Kimberly Kho, MD, MPH, of the University of Texas Southwestern Medical Center in Dallas, told 麻豆传媒 that selective progesterone receptor modulators (SPRMs) like mifepristone may be good options for treating adenomyosis, but there are still barriers to patient access.

"I do think that SPRMs in general have faced issues with being clinically available due to initial concerns about side effects with use, specifically changes in the endometrium, though this study, as well as others, have suggested that these changes, called 'progesterone receptor modulator-associated endometrial changes,' are benign and reversible," she said.

"In the U.S., despite its efficacy, and the short-term safety demonstrated in this study, I suspect that mifepristone may continue to face barriers to adoption due to its association with ," she added. "This is unfortunate, since there are few highly effective medical treatment options for women who suffer from adenomyosis-related symptoms."

For this multicenter double-blind study, 134 patients with adenomyosis pain symptoms were enrolled from 10 hospitals in China from May 2018 to April 2019. Participants were excluded if they had a history of undiagnosed vaginal bleeding outside the study reference ranges, had malignant endometrial tumors or uterine fibroids, or were diagnosed with endometriosis. Participants also had to agree to use only nonhormonal methods of birth control.

Of these patients, 126 were included in the efficacy analysis, with 61 patients (mean age 40.2) receiving mifepristone and 65 (mean age 41.7) receiving placebo.

Patients were randomized to receive either 10 mg of mifepristone or a placebo orally once daily for 12 weeks, and had regular trial visits every 4 weeks until 4 weeks after the trial concluded.

Zhang and team noted that the trial was only conducted in China, which potentially limited the applicability of its findings to other populations. Other limitations included their inability to conduct endometrial biopsies, for ethical reasons, as well as the short time period of the study. They encouraged further research to determine the drug's long-term efficacy and safety.

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