Background: Approximately one half of all women 35 to 49 years of age have fibroids, which are estimated to be responsible for more than 1.2 million hospitalizations per year with more than 1 million hysterectomies and countless other surgical and medical interventions. Symptoms can include heavy vaginal bleeding, anemia, and significant pain. The antiprogestin mifepristone (Mifeprex) has been noted to reduce uterine and fibroid size, diminish pain, and lessen bleeding; however, these benefits have not been conclusively demonstrated in a randomized controlled clinical trial, and an optimal dosage has not yet been established. Fiscella and colleagues conducted a placebo-controlled randomized trial of 5 mg mifepristone daily for symptomatic fibroids.
The Study: Through advertisements and contacts with community physicians, the study authors recruited premenopausal women who reported at least moderately severe fibroid-related symptoms. Eligibility criteria included a score of at least 39 on an established symptom scoring scale, uterine volume of 160 mL or more on ultrasonography, at least one fibroid measuring 2.5 cm or larger, and no recent use of hormones. Exclusion criteria included serious medical conditions, severe anemia, psychiatric illness or substance abuse, elevated hepatic enzymes, and pregnancy or intended pregnancy. All study participants agreed to use barrier contraception during the study.
The baseline assessment included full physical and pelvic examination, ultrasonography, endometrial biopsy, and biochemical assessment. Participants were randomly assigned treatment with mifepristone 5 mg daily or an identical-looking placebo. Analgesic use was permitted during the study, but participants were asked to record it.
The principal outcome measure was scoring change on the symptom/quality-of-life scale. Additional outcomes measured included scores for global health status and pain, as well as vaginal bleeding, which was assessed on logs and pictoral charts. Uterine and fibroid sizes were measured by ultrasonography at one, three, and six months; a pregnancy test was required monthly; hemoglobin and liver function tests were conducted at one, three, and six months; and endometrial biopsy was performed at six months.
Results: The 22 women assigned to the mifepristone therapy group and the 20 women assigned to the placebo group had comparable baseline characteristics, except that the treatment group had a higher average body mass index (32 compared with 26 kg per m2) and uterine volume (506 compared with 392 mL). Three women dropped out of the study immediately after randomization, and three more failed to complete the study; none dropped out because of adverse effects. Adherence was high in the remaining participants, with each group missing an average of only three days of treatment per month for any reason.
Both groups reported improvements in symptom-related quality of life, but the average improvement was significantly greater in the women in the treatment group (135 percent compared with 41 percent). Treatment with mifepristone also was associated with significantly greater gains in energy and health status and concomitant reductions in fatigue and pain. The subscales assessing physical functioning, emotional and physical health, and social functioning did not show significant differences between the two groups. The treatment group showed improvement on one pain scale, but this did not reach statistical significance. They also reported improvements in almost all symptoms, but only score differences for pelvic pressure and pain with intercourse were statistically significant.
Bleeding was significantly reduced during mifepristone therapy. By six months, 41 percent of women in the treatment group were amenorrheic compared with no women in the placebo group. Uterine volume decreased significantly (by an average of 200 mL) in the treatment group but increased by an average of 73 mL in the placebo group. Mean hemoglobin levels increased significantly during mifepristone therapy (from 12.0 to 13.5 g per dL [120 to 135 g per L]) but declined in the placebo group (from 12.2 to 11.6 g per dL [122 to 116 g per L]). The percentage of women with hemoglobin levels lower than 12 g per dL after six months of treatment had declined from 50 to 9 in the treatment group but increased from 45 to 60 in the placebo group.
The groups did not differ in analgesic use, and no endometrial hyperplasia or significant pathology was detected during the study. Adverse effects were uncommon in both groups.
Conclusion: The authors conclude that 5 mg mifepristone daily over six months was well tolerated and associated with significant improvements in quality of life; control of some symptoms; and objective measures of uterine size, bleeding, and anemia in women with fibroids. They call for larger studies over longer treatment periods to provide more data on the safety and acceptability of long-term mifepristone therapy for this common condition and to clarify the apparently selective effect on specific symptoms of fibroids.