[Show abstract][Hide abstract] ABSTRACT: There is growing interest in the use of progesterone receptor modulators such as mifepristone for treatment of gynecologic and other conditions, but interest in progesterone receptor modulators is dampened by the effects of the agents on the endometrium. In this study, we examined the endometria of women exposed to mifepristone for treatment of leiomyomas in doses of 2.5 and 5 mg and compared them to unexposed endometria. We assessed the reliability of these features by comparing agreement in ratings between pathologists who were blinded to each other's readings. We assessed distinguishing features between exposed and unexposed groups by comparing frequency of features between groups. We found that key features could be reliably assessed by pathologists experienced in endometrial pathology. We observed several features (nonsynchronous endometrium, large fluid filled glands, and abnormal blood vessels) that distinguished endometrial samples that were and were not exposed to the drug. These findings suggest several features that can be tracked during studies involving mifepristone and, potentially, other progesterone receptor modulators.
Human pathology 02/2011; 42(7):947-53. · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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
Obstetrics and Gynecology 12/2006; 108(6):1381-7. · 4.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The primary aim was to assess long-term effects of low-dose mifepristone on myoma regression, symptoms, and endometrial pathology. The secondary aim was to assess regrowth of myomas after cessation of mifepristone.
Prospective, open-label, randomized, controlled trial of 5 mg versus 10 mg mifepristone daily for 1 year, in women with large, symptomatic myomas, with variable follow-up among a subset of subjects (Canadian Task Force classification II-2).
University research group set in a community hospital.
Forty premenopausal women with large, symptomatic myomas.
Oral mifepristone 5 or 10 mg daily for 1 year.
Mean uterine volumes decreased in both groups by 48% after 6 months of mifepristone and by 52% to 53 % in both groups after 12 months. Amenorrhea occurred in 61% to 65% at 6 months, and 40% to 70 % at 12 months. Eighty endometrial biopsies were performed. Simple hyperplasia was seen in 5 (13.9 %) of 36 subjects at 6 months and 1 (4.8 %) of 21 at 12 months. All cases of hyperplasia occurred in the 10 mg group. No endometrial sample showed cytologic atypia. Nine women were followed posttreatment for an average of 5.7 months. Uterine volumes increased among most of these subjects, although they remained on average 42% less than baseline.
Long-term administration of low-dose mifepristone results in myoma shrinkage and amelioration of symptoms; modest rates of low-grade endometrial hyperplasia, but no evidence of premalignant potential, also occur. Regrowth occurs slowly following cessation of the drug.
[Show abstract][Hide abstract] ABSTRACT: To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms, and to measure side effects.
Forty premenopausal women with large, symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study. Uterine volume was measured at bimonthly intervals by sonography. Serum concentrations of hemoglobin levels, follicle-stimulating hormone, and liver enzymes were obtained, and endometrial samples, symptoms, and menstrual bleeding were also assessed.
Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study. Mean uterine volume shrank by 48% (P <.001) in the 5-mg group and 49% (P <.001) in the 10-mg group, a nonsignificant difference. Leiomyoma-related symptoms were comparably reduced in both groups. Amenorrhea occurred in 60-65% of both groups. Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group. Simple endometrial hyperplasia occurred in 28% of all subjects, with no difference between groups. No atypical hyperplasia was noted.
Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression, improvement in symptoms, and few side effects. Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone.
Obstetrics and Gynecology 02/2003; 101(2):243-50. · 4.80 Impact Factor