[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.
[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
No preview · Article · Dec 2006 · Obstetrics and Gynecology
[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.
No preview · Article · Jun 2005 · Journal of Minimally Invasive Gynecology
[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.
No preview · Article · Feb 2003 · Obstetrics and Gynecology
[Show abstract][Hide abstract] ABSTRACT: The study was conducted to determine whether the administration of mifepristone followed by vaginal misoprostol can induce an abortion in early pregnancy when no gestational sac is present on sonogram. This report presents a prospective, pilot study of 30 healthy adult women, pregnant and seeking an abortion, and with no gestational sac on sonogram. All women had a baseline serum chorionic gonadotropin (hCG) level measured prior to using mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 48 h later, and then returned up to 4 days later for a repeat sonogram and serum hCG level. Women with initial hCG levels > 2000 IU/L were evaluated for ectopic pregnancy. At the first follow-up visit, if the hCG decreased by >50%, the women were followed with home pregnancy (25 IU/L) tests weekly until negative. If the levels did not decrease by 50%, a second dose of misoprostol was given. Surgical intervention was indicated for persistent hCG levels or excessive bleeding. Of the 30 women enrolled, the mean number of days of amenorrhea was 40 (SD 9) days. Two women had surgical intervention for continuing pregnancy, 2 had ectopic pregnancies, and 1 was lost to follow-up. Complete medical abortions occurred in 25/30 (88%) women, but when recalculated, in 25/27 (93%) women who completed the protocol and who did not have an ectopic pregnancy. There was 1 adverse event in a woman with an ongoing pregnancy who then received methotrexate. She was hospitalized a day later with a complicated pelvic infection and likely methotrexate-induced pneumonitis. Twenty-three women had a decrease in hCG at first follow-up visit of >50%. All 27 women who completed the protocol found the overall regimen acceptable. Mifepristone followed at 48 h by vaginal misoprostol were effective and acceptable in inducing an abortion in very early pregnancy. There may be a higher incidence of failure in very early pregnancies. Documentation of a complete abortion by hCG level is necessary to ensure the pregnancy is neither ongoing nor ectopic.
[Show abstract][Hide abstract] ABSTRACT: The conventional timing of misoprostol administration after mifepristone for medical abortion is 2 days, but more flexible intervals, which may make the regimen more convenient, have not been studied.
To determine whether vaginal misoprostol administered 1, 2, or 3 days after mifepristone influences safety or effectiveness for abortion at up to 56 days' gestation.
Prospective, randomized, open-label trial conducted from March 1998 to June 1999.
Sixteen US primary care and referral abortion facilities.
A total of 2295 healthy patients aged 18 years or older who were 56 or fewer days pregnant. Forty (1.7%) were lost to follow-up.
Patients received 200 mg of oral mifepristone and were randomly assigned to self-administer 800 microg of vaginal misoprostol at home 1 (n = 745), 2 (n = 778), or 3 (n = 772) days later. Women returned to the clinic up to 8 days after mifepristone for ultrasonographic evaluation. A second dose of misoprostol was administered if the abortion was not complete. Patients with continuing pregnancy, excessive bleeding, or retained pregnancy tissue 5 weeks later received an aspiration curettage.
Effectiveness of the procedure (ie, a complete medical abortion without surgical intervention), adverse effects, acceptability of the procedure based on patient questionnaires, reasons for surgical intervention, and adverse outcomes, compared among the study groups.
Of the 2255 women completing follow-up, complete medical abortion rates were 98% (95% confidence interval [CI], 97%-99%) among those using misoprostol after 1 day, 98% (95% CI, 97%-99%) for those using misoprostol after 2 days, and 96% (95% CI, 95%-97%) among those using misoprostol after 3 days. Fifty-five subjects aborted before taking misoprostol, 9 had early surgery, and 103 did not take misoprostol on their assigned day. No blood transfusions were required. Cramping and nausea were the most common adverse effects reported, with similar percentages of patients in all 3 groups reporting such effects. Thirteen unexpected or serious adverse events occurred: 6 in those using misoprostol after 1 day; 4 in those using it after 2 days; and 3 in those using it after 3 days. Nearly all women (>90%) found the procedure to be acceptable.
Our results suggest that vaginal misoprostol, 800 microg, can be used from 1 to 3 days after mifepristone, 200 mg, for early medical abortion, and need not be administered strictly 48 hours after mifepristone. JAMA. 2000;284:1948-1953.
Full-text · Article · Oct 2000 · JAMA The Journal of the American Medical Association
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to compare the effectiveness, side effects, and acceptability of one-third the standard dose of mifepristone, i.e., 200 mg, and vaginal misoprostol 800 microg to induce abortion in subjects < or =56 days pregnant with subjects 57-63 days pregnant. A prospective multicenter trial enrolled healthy women > or =18 years, < or =63 days pregnant, and wanting an abortion. Women received mifepristone 200 mg orally, followed by misoprostol 800 microg vaginally, and returned 1-4 days later for ultrasound evaluation. A second dose of misoprostol was administered, if necessary. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, or persistent products of conception 5 weeks later. Of 1137 subjects, 829 were in the < or =56 days pregnant group and 308 in the 57-63 days pregnant group. In all, 34 subjects had surgical intervention and 16 were lost to follow-up. Complete medical abortions occurred in 97% of subjects < or =56 days pregnant and 96% in the 57-63 days pregnant group. In all, 88% of subjects in the < or =56 days pregnant and 92% in the 57-63 days pregnant group bled within 4 h of using vaginal misoprostol. Comparing subjects < or =56 days pregnant with 57-63 days pregnant, there was less diarrhea (20% vs 29%, p = 0.002) and vomiting (33% vs 44%, p = 0.001), although side effects were acceptable to 82% of subjects in both groups. One subject in the < or =56 day group required a transfusion for delayed excessive bleeding. Although bleeding (p = 0.01) and pain (p = 0.02) were less acceptable in the 57-63 day group, 91% of subjects in both groups reported that the overall procedure was acceptable. In summary, low-dose mifepristone 200 mg and home administration of vaginal misoprostol 800 microg at 48 h were highly effective and acceptable to women < or =63 days pregnant, thereby expanding the number of women who can access a medical abortion.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women > or = 18 years, up to 8 weeks pregnant, and wanting an abortion. The women received 200 mg mifepristone orally, self-administered 800 micrograms misoprostol vaginally at home 48 h later, and returned 1-4 days later for ultrasound evaluation. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, persistent products of conception 5 weeks later, or other serious medical conditions. Of the 933 subjects, 906 (97%) had complete medical abortions, 22 had surgical intervention, two were protocol failures, and three were lost to follow up. Of the 746 subjects who had no or minimal bleeding before misoprostol, 80% bled within 4 h and 98% within 24 h of using misoprostol. By day 7, 95% of women had a complete abortion. Side effects were aceptable in 85% of subjects, and 94% found the procedure acceptable. Low-dose mifepristone followed by vaginal misoprostol was highly effective as an abortifacient.
[Show abstract][Hide abstract] ABSTRACT: For women who require interruption of pregnancy, medications that can offer a safe alternative to surgery--for example, methotrexate (though interruption of pregnancy is not an approved indication) and mifepristone (formerly known as RU486 and currently pending approval by the Food and Drug Administration [FDA])--are being examined. As with any new therapy, clinicians who wish to be able to offer this option should become familiar with the medications' safety and efficacy profiles and how they work, which patients are acceptable candidates, how the procedure is performed, how to counsel women seeking information, and how to manage complications. Nonsurgical abortion using either methotrexate or mifepristone in combination with misoprostol can be a safe and effective alternative to surgical abortion if a woman is no more than 7 weeks pregnant, clinical guidelines are followed, and access to surgical abortion is available for complications. Administration of either agent is followed within days by administration of misoprostol, a prostaglandin that induces uterine contraction and expulsion of the uterine contents. Side effects of all 3 agents are generally mild, but complications may include ongoing pregnancy, incomplete abortion, or excessive bleeding.
No preview · Article · Oct 1997 · Medscape women's health
[Show abstract][Hide abstract] ABSTRACT: There have been no US studies published on the effectiveness, safety, time to bleeding, and acceptability of misoprostol administered by vagina at home and repeated, if needed, after mifepristone was administered for abortion in women up to 8 weeks pregnant.
A prospective trial was conducted with women up to 8 weeks pregnant wanting an abortion. After receiving mifepristone 600 mg orally, subjects self-administered vaginal misoprostol 800 micrograms at home 2 days later. Subjects returned within 7 days, and if the gestational sac was still present on ultrasound, a repeat dose of misoprostol was administered in the office. Subjects completed a daily symptom log and a questionnaire on the acceptability of the procedures.
Of the 166 subjects, 163 (98%) had a complete medical abortion. Three subjects presented with persistent bleeding and an incomplete abortion from 27 to 35 days after taking mifepristone and required surgical intervention. Vaginal spotting or bleeding occurred in 104 (62%) subjects before taking misoprostol, and 18 (11%) did not use misoprostol. Bleeding occurred on average 3.5 hours (SD, 3.2) after taking misoprostol. Six (4%) subjects required a second dose of misoprostol. Gastrointestinal side effects were common, mild, and brief. One hundred fifty-nine (96%) subjects agreed that the procedure went well, and 146 (90%) agreed that home administration of misoprostol was acceptable.
Two days after taking mifepristone, misoprostol administered by vagina was found to be safe, highly effective, and acceptable to women. Since only 6 subjects needed a second dose of misoprostol, conclusions about repeat doses are not possible. This procedure is a promising alternative to surgical abortion.
No preview · Article · May 1997 · The Journal of family practice
[Show abstract][Hide abstract] ABSTRACT: To determine whether methotrexate as a single agent for induced abortion in pregnancies up to 5 weeks is as effective, has fewer side effects and is as acceptable to subjects as the combination of methotrexate and misoprostol.
Women with no greater than a 5-week gestation were compared with a historical control group of consecutive women presenting for a medical abortion matched for gestational age. Subjects received intramuscular methotrexate on day 1. The study group received no misoprostol until day 21, when it was offered if the abortion had not yet occurred. The control group self-administered one or more doses of misoprostol within the first week after methotrexate. A complete abortion was defined by either negative transvaginal ultrasound or negative urine pregnancy test. All subjects completed a daily symptom log and satisfaction questionnaire. The analysis consisted of a comparison of the study group and control group for completion and timing of the abortion, symptoms and subject satisfaction.
There were 40 study subjects and 53 controls. All subjects had a medical abortion without surgery. Ten (25%) of the 40 study subjects reached study day 21 without bleeding: 4 used misoprostol and 6 chose to wait for the abortion to occur spontaneously. One of the 10 subjects had persistent embryonic cardiac activity at 21 days and aborted after misoprostol. The mean number of days to bleeding was 15.5 days (SD 7.8 days) for the study group as compared with 8.1 days (SD 11.3) (P = .0003) for the control group. There was no significant difference in the number of days of bleeding, gastrointestinal side effects or reported subject satisfaction.
While methotrexate as a single agent was effective in inducing abortion in early pregnancy, 15% of the study subjects finally used misoprostol, the abortion took significantly longer, and side effects were not less common as compared with those in subjects who received the combination of methotrexate and misoprostol.
No preview · Article · Feb 1997 · The Journal of reproductive medicine
[Show abstract][Hide abstract] ABSTRACT: This study examined the effectiveness of an abortion by methotrexate and misoprostol, including side effects, subjects' satisfaction, and optimal treatment strategies.
The study evaluated a prospective ongoing trial of women with an 8-week gestation or less wanting an abortion. Subjects received intramuscular methotrexate (50 mg per m2 of body surface area) on day 1. Subjects self-administered misoprostol 800 micrograms orally or as a vaginal suppository or vaginal tablets either on day 3 to 4 or day 5 to 7. Repeat misoprostol 800 micrograms doses were used vaginally if there was no significant bleeding and the gestation was less than 12 weeks. Subjects with continuing pregnancies had a surgical abortion. Subjects completed a daily symptom log and a satisfaction questionnaire. A successful medical abortion was defined by vaginal bleeding without surgical intervention and either a negative urine pregnancy test or a negative transvaginal ultrasound.
Of the 282 subjects, 274 (97%) had a medical abortion. Eight (3%) subjects required surgical intervention--four for continued pregnancies and four for excessive bleeding. One hundred and sixty-two (57%) subjects required only one dose of misoprostol and started bleeding, on average, 6.2 hours later. One hundred and twelve subjects (40%) required an average of 2.5 misoprostol doses and started bleeding, on average, 12.4 days after initial methotrexate injection. Misoprostol was more effective vaginally than orally. Gastrointestinal side effects were common, mild, and brief. Eighty-eight percent of the subjects agreed that the procedure went well. Subjects monitored with ultrasound completed the study sooner than those followed by beta-hCG levels.
Methotrexate and misoprostol were effective in inducing an abortion up to 8 weeks' gestation. The procedure is a promising alternative to surgical abortion.
[Show abstract][Hide abstract] ABSTRACT: To describe the use of methotrexate and misoprostol to induce abortion in pregnancies up to 8 weeks when uterine or cervical anomalies make suction curettage difficult or impossible.
Four consecutive women, 8 weeks pregnant or less and with failed suction curettage, were given methotrexate 50 mg per square meter intramuscularly followed by a misoprostol 800-microgram suppository 72 hours later. A repeat dose of a misoprostol 800-microgram vaginal suppository was administered on day 4 if there was no bleeding, and an additional dose was given if the repeat beta-hCG titer had not decreased by at least 50%. Subjects were followed-up with serum or urine hCG assays. Complete abortion was defined by vaginal bleeding and a negative urine pregnancy test. Subjects completed a daily symptom log and a satisfaction questionnaire when the abortion was complete.
The four women referred after failed suction curettage had the following anatomic problems: a uterus bicornis bicollis, a bicornuate uterus, uterine leiomyomas, and cervical stenosis resulting from previous laser surgery. All subjects had a complete abortion from methotrexate and misoprostol. Mild gastrointestinal side effects were reported by all four subjects: nausea (two subjects), vomiting (two), and diarrhea (two). The satisfaction questionnaire revealed that all subjects agreed with the statements that "Overall, the procedure went well" and "I would recommend this procedure over a surgical abortion."
Methotrexate and misoprostol can induce an abortion when uterine or cervical anomalies make suction curettage difficult or impossible.
No preview · Article · Apr 1996 · Obstetrics and Gynecology
[Show abstract][Hide abstract] ABSTRACT: To determine the effectiveness and side effects of and subject satisfaction with an induced abortion by administration of methotrexate and intravaginal misoprostol.
Prospective trial of 100 consecutive pregnant women aged 18 years or older at 8 weeks' gestation or less and wanting an abortion.
Intramuscular administration of 50 mg of methotrexate per square meter of body surface area on day 1 and a misoprostol 800-micrograms vaginal suppository on day 3. Administration of misoprostol was repeated the following day if no bleeding occurred after the first dose.
After pregnancy dating by clinical criteria, subjects were followed up with serum beta-human chorionic gonadotropin (beta-hCG) determinations on days 1, 7, and 14 and a high-sensitivity urine hCG test every 2 weeks until the value was less than 10 IU/L. Subjects completed a daily symptom log and satisfaction questionnaire on day 14.
Complete abortion as defined by vaginal bleeding and a beta-hCG value of less than 10 IU/L without surgical intervention, complications and side effects, and patient satisfaction.
Ninety-seven subjects had a complete abortion and one subject had vaginal bleeding and a 94% decrease of her beta-hCG value on day 7 but was subsequently unavailable for follow-up. Two subjects required surgical procedures: one with a continued pregnancy and one for excessive bleeding. No failures or complications occurred in early gestations prior to 45 days from the last menstrual period. Seventy-three percent responded to misoprostol treatment with bleeding within 12 hours and had a mean decrease of 90% in their beta-hCG value on day 7. Twenty-seven percent had no immediate bleeding response to misoprostol administration, began bleeding on day 10 (SD, 8 days), and had a mean decrease of 10% in their beta-hCG value on day 7. Seventy percent reported nausea; 46%, diarrhea; and 23%, vomiting. Ninety-three percent agreed that the procedure was acceptable and 95% would recommend the procedure.
Methotrexate and misoprostol were effective in inducing an abortion up to 8 weeks. Home administration of a compounded misoprostol vaginal suppository was successful. Although gastrointestinal tract side effects were common, women found the procedure and its side effects acceptable.
No preview · Article · Oct 1995 · Archives of Family Medicine