Regression of uterine leiomyomata to the antiprogesterone RU486: dose-response effect

Abstract

Objective: To study the response of uterine leiomyomata to three daily doses of RU486 (5, 25, and 50 mg).

Design: Prospective nonrandomized trial of women with symptomatic leiomyomata.

Setting: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center.

Patients: Ten patients with symptomatic leiomyomata previously reported after treatment with 50 mg of RU486 daily for 3 months. Eleven patients treated with 25 mg of RU486 daily and nine patients placed on 5 mg of RU486 daily for 12 weeks.

Main outcome measures: Changes in leiomyomata volume as measured with vaginal ultrasounds at baseline and monthly thereafter. Frequent blood samples for hematology, chemistry, and hormone levels were obtained. Twenty-four-hour urine collections for free cortisol and creatinine were obtained at baseline and at 12 weeks.

Results: All three doses induce ovarian acyclicity. Administration of 50 mg of RU486 decreases leiomyomata volume to 78.1% +/- 4.8% of baseline at 4 weeks, 60.5% +/- 6.6% at 8 weeks, and 51.0% +/- 9.2% after 12 weeks of treatment. Regressive response in patients treated with 25 mg of RU486 daily was 76.3% +/- 5.0% of baseline at 4 weeks, 54.0% +/- 5.1% at 8 weeks, and 44.0% +/- 5.0% after 12 weeks. At 5 mg of RU486 leiomyomata volume was 80.6% +/- 8.3% of baseline after 4 weeks, 63.7% +/- 14.6% after 8 weeks, and 74.4% +/- 19.8% after 12 weeks of therapy.

Conclusions: Although acyclicity is seen at all three doses, an effective dose to cause a clinically significant (50%) decrease in leiomyomata volume appears to be 25 mg daily.

PIP: The author report their findings from a study of the effect of RU486 on uterine leiomyomata volume. The authors previously reported an inhibitory effect of RU486 on the growth of uterine leiomyomata in 10 patients with symptomatic leiomyomata receiving 50 mg daily for 12 weeks. Findings are now reported on the effect of 5 mg and 25 mg daily doses of RU486 in 9 and 11 patients, respectively. Subjects were patients at the University of California, San Diego Medical Center. Vaginal inhibitory at baseline and monthly thereafter were used to measure changes in leiomyomata volume. Frequent blood samples for hematology, chemistry, and hormone levels were obtained, as well as 24-hour urine collections to assess free cortisol and creatinine at baseline and 12 weeks. All three doses induce ovarian acyclicity. Administration of 50 mg of RU486 decreases leiomyomata volume to 78.1% of baseline at 4 weeks, 60.5% at 8 weeks, and 51.0% after 12 weeks of treatment. Administration of 25 mg of RU486 decreases leiomyomata volume to 76.3% of baseline at 4 weeks, 54.0% at 8 weeks, and 44.0% after 12 weeks of treatment. Administration of 5 mg of RU486 decreases leiomyomata volume to 80.6% of baseline at 4 weeks, 63.7% at 8 weeks, and 74.4% after 12 weeks of treatment. 25 mg daily appears to be the effective dose to cause a clinically significant 50% decrease in leiomyomata volume.