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Archives of Family Medicine 1998Mifepristone (RU 486) has received recent attention for its effects as an abortifacient. Mifepristone has not yet been approved for use in the United States. The Food... (Review)
Review
Mifepristone (RU 486) has received recent attention for its effects as an abortifacient. Mifepristone has not yet been approved for use in the United States. The Food and Drug Administration issued an "approvable letter" in September 1996, but mifepristone will not be available in the United States until a new manufacturer is found. Experience with mifepristone is extensive in Europe, and there have been retrospective studies and large, controlled clinical trials of its efficacy. It is most efficacious when administered to women who are less than 8 weeks pregnant, in a single 600-mg oral dose followed 48 hours later by administration of intravaginal misoprostol. This regimen has a success rate of 98%, as do most surgical abortive procedures. The most frequent adverse effect is painful contractions, which occur in up to 93% of women, with oral analgesia required in as many as half the cases. Large-scale surveys of women who elected medical abortion reported high patient satisfaction. Mifepristone is likely to have additional clinical uses. Researchers are exploring mifepristone's potential uses in cervical ripening and labor induction; contraception; delivery after intrauterine demise; treatment of breast cancer, unresectable meningioma, and prostate cancer; amelioration of endometriosis; and management of Cushing syndrome.
Topics: Abortifacient Agents, Steroidal; Contraceptives, Oral, Synthetic; Contraceptives, Postcoital, Synthetic; Female; Hormone Antagonists; Humans; Mifepristone; Pregnancy
PubMed: 9596454
DOI: 10.1001/archfami.7.3.219 -
Obstetrical & Gynecological Survey Oct 2022Mifepristone (RU-486) is a selective progesterone receptor modulator that has antagonist properties on the uterus and cervix. Mifepristone is an effective abortifacient,...
IMPORTANCE
Mifepristone (RU-486) is a selective progesterone receptor modulator that has antagonist properties on the uterus and cervix. Mifepristone is an effective abortifacient, prompting limitations on its use in many countries. Mifepristone has many uses outside of induced abortion, but these are less well known and underutilized by clinicians because of challenges in accessing and prescribing this medication.
OBJECTIVES
To provide clinicians with a history of the development of mifepristone and mechanism of action and safety profile, as well as detail current research on uses of mifepristone in both obstetrics and gynecology.
EVIDENCE ACQUISITION
A PubMed search of mifepristone and gynecologic and obstetric conditions was conducted between January 2018 and December 2021. Other resources were also searched, including guidelines from the American College of Obstetricians and Gynecologists and the Society of Family Planning.
RESULTS
Mifepristone is approved by the Food and Drug Administration for first-trimester medication abortion but has other off-label uses in both obstetrics and gynecology. Obstetric uses that have been investigated include management of early pregnancy loss, intrauterine fetal demise, treatment of ectopic pregnancy, and labor induction. Gynecologic uses that have been investigated include contraception, treatment of abnormal uterine bleeding, and as an adjunct in treatment of gynecologic cancers.
CONCLUSIONS AND RELEVANCE
Mifepristone is a safe and effective medication both for its approved use in first-trimester medication abortion and other off-label uses. Because of its primary use as an abortifacient, mifepristone is underutilized by clinicians. Providers should consider mifepristone for other indications as clinically appropriate.
Topics: Abortifacient Agents; Abortion, Induced; Female; Gynecology; Humans; Mifepristone; Obstetrics; Pregnancy; Receptors, Progesterone
PubMed: 36242531
DOI: 10.1097/OGX.0000000000001063 -
BioMed Research International 2015We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma... (Review)
Review
OBJECTIVES
We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients.
MATERIALS AND METHODS
A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014. Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition.
RESULTS
A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered.
CONCLUSIONS
No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients' selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required.
Topics: Animals; Disease Management; Humans; Meningioma; Mifepristone; Progesterone; Receptors, Progesterone
PubMed: 26146614
DOI: 10.1155/2015/267831 -
Journal of Midwifery & Women's Health 2002In September 2000, the U.S. Food and Drug Administration (FDA) approved the use of mifepristone for the provision of medical abortion. Although mifepristone was... (Review)
Review
In September 2000, the U.S. Food and Drug Administration (FDA) approved the use of mifepristone for the provision of medical abortion. Although mifepristone was developed and marketed because of its potential to effect early first-trimester medical abortion, it has additional applications to health care, including the treatment of gynecologic conditions, cancer, and Cushing's disease. The controversial nature of abortion has dominated the publicity about mifepristone. The evidence for the safety and efficacy of mifepristone in medical abortion has been overshadowed, and many clinicians are unaware of the other potential uses of the drug. This article provides a discussion of background information on the pharmacology, development of, and research on mifepristone and an update on current and potential uses in health care today. Information on the FDA-approved regimen and alternative protocols for management of mifepristone in its use in abortion care are presented.
Topics: Abortifacient Agents, Steroidal; Abortion, Induced; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Midwifery; Mifepristone; Misoprostol; Patient Education as Topic; Physician's Role; Pregnancy; United States; United States Food and Drug Administration
PubMed: 12484667
DOI: 10.1016/s1526-9523(02)00331-8 -
International Journal of Environmental... Sep 2021Interstitial pregnancy is defined as the presence of a gestational sac in the most proximal section of the fallopian tube. Management of interstitial pregnancy remains a... (Review)
Review
Interstitial pregnancy is defined as the presence of a gestational sac in the most proximal section of the fallopian tube. Management of interstitial pregnancy remains a debated topic. Depending on hemodynamic stability, size of pregnancy, depth of surrounding myometrium, and desires for future fertility, interstitial pregnancy can be managed medically or surgically. We reviewed the literature in December 2020 using keywords "interstitial pregnancy", "medical treatment", "methotrexate", and "mifepristone". Articles published from January 1991 until 2020 were obtained from databases EMBASE, SCOPUS, and PUBMED. We describe the case of a patient with an interstitial pregnancy that was managed with a total medical approach in August 2020 at Burlo Garofolo Hospital. The patient was asymptomatic and hemodynamically stable, with a high level of serum -hCG (22,272 mUi/mL). We used the combination of methotrexate (MTX) and mifepristone. Medical therapy was effective leading to interstitial pregnancy resolution in 51 days without collateral effects for the patient. We found seven previous cases reported in the literature. Our purpose is to underline the efficacy of medical therapy with systemic multidose MTX associated with a single oral dose of mifepristone and also folinic acid when is present a viable fetus and a high serum -hCG level.
Topics: Female; Fertility; Humans; Methotrexate; Mifepristone; Myometrium; Pregnancy; Pregnancy, Interstitial
PubMed: 34574706
DOI: 10.3390/ijerph18189781 -
Obstetrics and Gynecology Jun 2004To systematically review the effect of mifepristone on uterine leiomyoma size and symptoms and to summarize its adverse effects. (Review)
Review
OBJECTIVE
To systematically review the effect of mifepristone on uterine leiomyoma size and symptoms and to summarize its adverse effects.
DATA SOURCES
A computerized search in MEDLINE, EMBASE, LILACS, and Cochrane databases from 1985 to 2002 and hand searches of conference proceedings from 1995 to 2002 were performed with the search terms "mifepristone" and "leiomyomata" and publication type "clinical trial."
METHODS OF STUDY SELECTION
Titles and abstracts were reviewed by 2 authors; there were no areas of disagreement. Inclusion criteria were clinical trials of daily mifepristone for uterine leiomyomata that measured uterine or leiomyoma volume before and after treatment.
TABULATION, INTEGRATION, AND RESULTS
Data from each article were abstracted by 2 reviewers. The search identified 6 before-and-after clinical trials involving a total of 166 women with symptomatic uterine leiomyomata. The subjects received 5 to 50 mg/d of mifepristone for 3 to 6 months. No study was placebo-controlled or blinded. Meta-analytic techniques were not performed due to variation in outcome and mifepristone dose. Daily treatment with all doses of mifepristone resulted in reductions in uterine and leiomyoma volumes ranging from 27% to 49% and 26% to 74%, respectively. Mifepristone treatment reduced the prevalence and severity of dysmenorrhea, menorrhagia, and pelvic pressure. Rates of amenorrhea ranged from 63% to 100%. Transient elevations in transaminases occurred in 4%. Endometrial hyperplasia was detected in 10 (28%) of 36 women screened by endometrial biopsy.
CONCLUSION
Published trials of mifepristone showed reduction in leiomyoma size and improvement in symptoms. A notable adverse effect of mifepristone was development of endometrial hyperplasia.
Topics: Adult; Clinical Trials as Topic; Endometrial Hyperplasia; Female; Hormone Antagonists; Humans; Leiomyoma; Middle Aged; Mifepristone; Uterine Neoplasms
PubMed: 15172874
DOI: 10.1097/01.AOG.0000127622.63269.8b -
Archives of Gynecology and Obstetrics Feb 2019To investigate the molecular mechanisms governing aquaporin-1 (AQP1)-mediated, mifepristone-induced angiogenesis and improve the understanding of low-dose mifepristone...
PURPOSE
To investigate the molecular mechanisms governing aquaporin-1 (AQP1)-mediated, mifepristone-induced angiogenesis and improve the understanding of low-dose mifepristone serving as an anti-implantation contraceptive drug.
METHODS
Human umbilical vein endothelial cells (HUVECs) were used to explore the effects of different concentrations of mifepristone (0, 65, and 200 nmol/L) on the activity of angiogenesis. Forty-five pregnant mice during the "window of implantation" were treated with different concentrations of mifepristone. HUVECs' proliferation was examined using a methyl thiazolyl tetrazolium (MTT) assay. The microvessel density (MVD) and the expression of AQP1 in endometrium were determined with immunohistochemical methods.
RESULTS
The MVD and the expression of AQP1 were significantly higher than controls. Mifepristone at 200 nmol/L significantly affected HUVECs' proliferation during culture over 12 h, and pretreatment with AQP1-specific siRNA significantly inhibited the mifepristone-enhanced cell proliferation.
CONCLUSIONS
Low-dose mifepristone increased angiogenesis in a manner involving AQP1. This affords a new insight into the molecular mechanism underpinning the angiogenic effects of low-dose mifepristone.
Topics: Animals; Aquaporin 1; Contraceptives, Oral, Synthetic; Embryo Implantation; Female; Humans; Mice; Mifepristone; Neovascularization, Pathologic
PubMed: 30569345
DOI: 10.1007/s00404-018-4989-9 -
Perspectives on Sexual and Reproductive... Sep 2023Early pregnancy loss (EPL) affects 1 million patients in the United States (US) annually, but integration of mifepristone into EPL care may be complicated by regulatory...
CONTEXT
Early pregnancy loss (EPL) affects 1 million patients in the United States (US) annually, but integration of mifepristone into EPL care may be complicated by regulatory barriers, practice-related factors, and abortion stigma.
METHODS
We conducted qualitative, semi-structured interviews among obstetrician-gynecologists in independent practice in Massachusetts, US on mifepristone use for EPL. We recruited participants via professional networks and purposively sampled for mifepristone use, practice type, time in practice, and geographic location within Massachusetts until we reached thematic saturation. We analyzed interviews using inductive and deductive coding under a thematic analysis framework to identify facilitators of and barriers to mifepristone use.
RESULTS
We interviewed 19 obstetrician-gynecologists; 12 had used mifepristone for EPL and 7 had not. Participants were in private practice (n = 12), academic practice (n = 6), or worked at a federally qualified health center (n = 1). Seven had fellowship training, including four in complex family planning. The most common facilitators of mifepristone use for EPL were access to the expertise or protocols of local-regional experts, leadership from a "champion," prior experience with abortion care, and hospital capacity constraints during the COVID-19 pandemic. The most common barriers were related to the Mifepristone Risk Evaluation and Mitigation Strategy (REMS) Program imposed by the US Food and Drug Administration (FDA). Additionally, mifepristone's affiliation with abortion was a barrier to its use in EPL for some obstetrician-gynecologists.
CONCLUSION
The FDA Mifepristone REMS Program presents substantial barriers to obstetrician-gynecologists incorporating mifepristone into their EPL care.
Topics: Pregnancy; Female; Humans; United States; Mifepristone; Abortion, Spontaneous; Pandemics; COVID-19; Abortion, Induced; Massachusetts
PubMed: 37394759
DOI: 10.1363/psrh.12237 -
Lancet (London, England) Apr 2023
Topics: Humans; Female; Pregnancy; United States; Mifepristone; Abortion, Induced; United States Food and Drug Administration
PubMed: 37088084
DOI: 10.1016/S0140-6736(23)00813-9 -
Medicinal Research Reviews Sep 2014Mifepristone (RU486) is a born-for-woman molecule discovered three decades ago. Unlike those antihypertensive and antipsychotic pharmaceutical blockbusters, this... (Review)
Review
Mifepristone (RU486) is a born-for-woman molecule discovered three decades ago. Unlike those antihypertensive and antipsychotic pharmaceutical blockbusters, this abortifacient offers relatively low profit potential. Current understanding of mechanism of action of mifepristone and its on-going clinical trials are changing our views on the drug beyond its abortifacient scope. Here we briefly review its metabolism and pharmacokinetic properties including its unique enterohepatic circulation, its mechanisms of actions involving antiprogesterone and antiglucocorticoid, growth inhibition of various cancer cell lines, suppression of invasive and metastatic cancer potential, downregulation of Cdk2, Bcl-2, and NF-kappa B, interference of heterotypic cell adhesion to basement membrane, and cell migration. We comprehensively analyze recent results from preclinical and clinical studies using mifepristone as an anticancer drug for breast, meningioma, and gliomas tumors in the central nervous system, prostate cancer, ovarian and endometrial cancer, and gastric adenocarcinoma. Although mifepristone has more benefits for global public health than we originally thought, its effect as a postmetastatic chemotherapeutic agent is limited. Nonetheless, owing to its unique safe, metabolism and other pharmacological properties, metapristone (the primary metabolite of mifepristone) may have potential for cancer metastatic chemoprevention.
Topics: Abortifacient Agents, Steroidal; Abortion, Therapeutic; Female; Humans; Liver; Mifepristone; Neoplasm Metastasis; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 24585714
DOI: 10.1002/med.21311