Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial. Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel. Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial. Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial. Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel). Pregnancy termination with mifepristone and gemeprost: a multicenter comparison between repeated doses and a single dose of mifepristone. World Health Organization. A pilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon.
Uterine leiomyomas are widely prevalent and frequently cause menorrhagia. The major therapeutic option today is hysterectomy. Medical options are of highest interest.
                A total of 30 women with uterine leiomyomas scheduled for surgical intervention were randomized to receive either 50 mg mifepristone or placebo every other day during 3 months prior to surgery. Uterine blood flow and leiomyoma volume were evaluated once a month until surgery. Endometrial biopsies were obtained prior to and at end of treatment. Relevant biochemistry, symptoms and bleeding were recorded. Primary outcome was reduction in uterine leiomyoma size.
                There was a significant percentual decrease (P = 0.021) in the total leiomyoma volume in the mifepristone-treated group, -28 (-48, -8) % (mean +/- 0, 95 confidence interval), compared with the control group values 6 (-13, 25) %. Mifepristone treatment significantly reduced the bleeding days (P = 0.001) and increased serum haemoglobin values (P = 0.046). Serum cortisol levels remained unchanged, while a mild increase in serum androgens was noted. Endometrial biopsies showed no premalignant changes or changes in mitotic indices.
                Mifepristone may offer an effective treatment option for women with uterine leiomyoma and the associated pronounced uterovaginal bleeding. Clinical Trials identifier: www.clinicaltrials.gov: NCT00579475. It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time. To assess the effect of low-dose mifepristone on quality of life, pain, bleeding, and uterine size among women with symptomatic leiomyomata.
                Forty-two women with symptomatic uterine leiomyomata and uterine volume of 160 mL or more were randomized to mifepristone, 5 mg daily, or placebo for 26 weeks. Quality of life (Uterine Fibroid Symptoms Quality of Life Questionnaire and Medical Outcomes Study 36-Item Short Form survey) and uterine and leiomyoma size (ultrasonography) were assessed at baseline, and at 1 month, 3 months, and 6 months of treatment. Bleeding (daily logs and pictorial charts) and pain (McGill Pain Questionnaire) were assessed monthly. Endometrial pathology was assessed at baseline and 6 months.
                Forty-two women were randomized; 37 women completed all 6 months. Women randomized to mifepristone showed an improvement in leiomyoma-specific quality of life. Forty-one percent became amenorrheic, rates of anemia improved, and adjusted uterine size was reduced by 47%. Compared with the placebo group, improvements in these outcomes in the treatment group were significantly greater (P<.05 to .001). There were no significant differences in adverse effects between the groups. No endometrial hyperplasia was noted in any participant.
                Low-dose mifepristone improves leiomyoma-specific quality of life and reduces leiomyoma size among women with symptomatic leiomyomata.
                ClinicalTrials.gov www.clinicaltrials.gov NCT00133705
                I. To evaluate the effect of low-dose mifepristone on leiomyoma-related symptoms, uterine and leiomyoma in women with symptomatic leiomyomata.
                In a double-blind placebo-controlled trial, 40 patients with symptomatic leiomyoma and normal endometrial histology were randomised to receive 10 mg mifepristone (group 1) or placebo (group 2) daily for three months. Leiomyoma-related symptoms, uterine, leiomyoma and largest leiomyoma volumes were assessed at baseline and every month for three months. Endometrial biopsy was repeated at the end of therapy.
                Significant change was noticed between the two groups for mean menstrual blood loss (MBL) by first month. Menstrual blood loss declined by 94.8% in group 1 at three months and 84.2% patients attained amenorrhoea in this group. In group 1 complete relief of dysmenorrhoea occurred in significant number of women (80%) but only 33% patients got rid of pelvic pain. There was no change in these symptoms in group 1 Backache, urinary complaints and dyspareunia were not relieved in either group. Uterine, leiomyoma and largest leiomyoma volume declined by 26-32% in group 1 as compared to none in group 2, and this difference was statistically significant only by the end of the third month of therapy. Mean haemoglobin increased from 9.5 to 11.2 g/dL in group 1. In group 1, at the end of therapy, 63.1% of patients had endometrial hyperplasia without atypia.
                Ten milligrams mifepristone for three months is effective in reducing MBL, increasing haemoglobin and reducing uterine and leiomyoma volume with side-effect of endometrial hyperplasia. Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive with worldwide availability. However, it is associated with a high incidence of breakthrough bleeding (BTB) during the first 6 months of use which often leads to discontinuation. Mifepristone is a progesterone receptor antagonist that has been demonstrated to decrease BTB caused by the levonorgestrel subdermal implant (Norplant). The purpose of this study was to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with bleeding intervals > or =8 and > or =14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors. Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that provides an effective medical method of inducing abortion in early pregnancy. Since progesterone is essential for implantation, we tested the use of mifepristone for emergency postcoital contraception.
                We studied 800 women and adolescents requesting emergency postcoital contraception who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 micrograms of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy), and 402 women and adolescents were randomly assigned to receive 600 mg of mifepristone.
                None of the women and adolescents who received mifepristone became pregnant, as compared with four of those who received standard therapy; the difference in failure rates between the two regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (P less than 0.001). In many subjects the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40 percent vs. 60 percent) and vomiting (3 percent vs. 17 percent) on the day of treatment, as well as lower rates of other side effects, than the subjects treated with the standard regimen, but they were more likely to have a delay in the onset of the next menstrual period (42 percent vs. 13 percent).
                Mifepristone is a highly effective postcoital contraceptive agent that, if used more widely, could help reduce the number of unplanned and unwanted pregnancies. The acceptability and continuation rate of oral contraceptive steroids are limited by unpredictable bleeding and the fear of long-term risks such as breast cancer. By inhibiting ovulation and by altering the receptivity of the endometrium, antagonists of progesterone, such as mifepristone, could be developed as estrogen-free novel contraceptives.
                Multicentre, double-blind, randomized controlled trial comparing frequency of amenorrhoea (primary outcome), bleeding patterns, side effects and efficacy in women taking daily 5 mg mifepristone (n = 73) or 0.03 mg levonorgestrel (progestogen-only pill; POP, n = 23) for 24 weeks.
                More women were amenorrhoeic while taking mifepristone than POP (49 versus 0% P < 0.001), and fewer women bled or spotted for >5 days per month (4 versus 39% P < 0.001). Forty-eight percent of women who took mifepristone for 6 months had cystic glandular dilatation of the endometrium but none showed hyperplasia or atypia. There were no pregnancies in 356 months of exposure in women who used only mifepristone for contraception. Two pregnancies occurred in women taking mifepristone who were also using condoms for dual protection.
                Daily mifepristone (5 mg) is an effective oral contraceptive pill which has a better pattern of menstrual bleeding than an existing POP (levonorgestrel). To compare two regimens of mifepristone plus gemeprost for early pregnancy termination.
                A prospective, randomized, multicenter trial.
                Ten gynecological services, mostly in academic hospitals.
                Three hundred eighty-five healthy women up to 35 years of age with amenorrhea less than or equal to 49 days requesting pregnancy termination.
                Mifepristone, 25 mg five times at 12-hour intervals (n = 192) or 600 mg as a single dose (n = 193) followed by 1 mg gemeprost 60 hours after the start of mifepristone.
                Pregnancy outcome, time of onset and duration of vaginal bleeding, subjective complaints, and hormone changes during treatment and 6-week follow-up.
                Treatment outcome was identical in both groups with an overall complete abortion rate of 92.7% among the 385 women included in the analysis. The frequency of complaints, bleeding patterns, and changes in hemoglobin, beta-human chorionic gonadotropin, estradiol, and progesterone were also similar in both groups. Cortisol (at 12 and 36 hours after mifepristone) and prolactin (at 12 hours) were significantly higher in the single 600-mg dose group.
                When used for early pregnancy termination with prostaglandin, a lower dose of mifepristone than the currently recommended single 600-mg dose may suffice. The major side-effect of progestogen-only contraception is disruption of menstrual bleeding patterns, which can lead to a high incidence of early discontinuation. The aim of this study was to compare three treatments with placebo on the duration and recurrence of frequent and/or prolonged bleeding in Implanon users.
                Women between the ages of 18 and 45 years, who had used Implanon for > or =3 months and were experiencing prolonged or frequent bleeding patterns, were recruited at four Australian sites. Subjects were randomized to treatment using computer-generated random number table if they met the World Health Organization criteria for prolonged and/or frequent bleeding in the previous 90 days [Belsey, E.M., Pinol, A.P.Y. and Taskforce on Long-Acting Systemic Agents for Fertility Regulation, World Health Organization (1997) Contraception 55,57-65]. Treatments were: (1) mifepristone 25 mg given twice on day 1 followed by 4 days of twice daily placebo; (2) mifepristone 25 mg given twice on day 1 followed by 4 days of ethinyl estradiol (EE) 20 microg in the morning and placebo at night; (3) doxycycline 100 mg twice daily for 5 days; and (4) placebo twice daily for 5 days. Analysis was by intention to treat. The primary endpoint was the number of days of bleeding and spotting immediately following initiation of the 5 day course of each active therapy compared with placebo.
                A total of 179 women was assigned to treatment. Both mifepristone in combination with EE and doxycycline alone were significantly more effective in stopping an episode of bleeding {mean 4. 3 days [confidence interval (CI) 3.5-5.2], and 4.8 days (CI 3.9-5.8) respectively} than mifepristone alone or placebo [5.9 days (CI 4.8-7.2) and 7.5 days (CI 6.1-9.1) respectively]. No effect on subsequent bleeding patterns was observed in any treatment group.
                Both mifepristone plus EE and doxycycline alone were significantly more effective than placebo in terminating an episode of bleeding in women with prolonged and/or frequent bleeding using Implanon. We believe that the observed reduction in the number of bleeding days by almost 50% compared to placebo in both the mifepristone combination group and the doxycycline group demonstrates a clinically significant improvement in bleeding patterns and that further trials are needed to compare different combinations of therapy as well as multiple dosing regimens in order to establish which is the most effective treatment option. The effect of repeat administration or combinations of these preparations on long-term bleeding patterns requires further investigation.
Mifepristone reduced heavy menstrual bleeding and improved fibroid-specific quality of life. However, it was not found to reduce fibroid volume. Further well-designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids.