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Journal of Ethnopharmacology Aug 2023Threatened abortion is a common disease among women of childbearing age. Its high incidence rate and unclear etiology, seriously threaten women's physical and mental...
ETHNOPHARMACOLOGICAL RELEVANCE
Threatened abortion is a common disease among women of childbearing age. Its high incidence rate and unclear etiology, seriously threaten women's physical and mental health. Shoutai Wan (STW) is a traditional Chinese medicine decoction for treating abortion. It has a long history of treating threatened abortion by tonifying the kidney and calming the fetus. However, the mechanism of STW remains unclear.
AIM OF STUDY
To study the mechanism and potential benefit of STW in pregnant mice with hydrocortisone and mifepristone-induced threatened abortion.
MATERIALS AND METHODS
The STW compounds were identified using gas chromatography-mass spectrometry analysis. STW-H, STW-M, or STW-L was separately given 3 mg/ml, 1.5 mg/ml and 0.75 mg/ml STW in the morning, and 2 mg/ml hydrocortisone in the afternoon from gestation day (D) 1-9 and once with 0.4 mg/kg mifepristone on D10. Didroxyprogesterone (0.1 mg/ml) and equal dose pure water were used to replace STW in didroxyprogesterone (DYD) group and model group respectively. The control group used pure water to replace STW, hydrocortisone, and mifepristone. We performed morphological and histological analyses of the maternal-fetal interface on day 10.
RESULTS
The embryo loss rate in the STW-H and DYD groups was lower than that in the model group. Hematoxylin and eosin (HE) staining suggested that the morphology of maternal-fetal interface was improved in the STW-H and DYD groups. Immunohistochemical (IHC), Quantitative Reverse Transcription Polymerase Chain Reactionstaining (qRT-PCR), and Western blot (WB) results indicated that HIF-1α expression in the maternal-fetal interface of the STW-H and DYD groups was higher than that in model group. The activities of HK, PKM, LDH and the concentration of lactic acid in the STW-H and DYD groups were higher than those in model group. Furthermore, the protein and mRNA levels of HK2, PKM2, LDHA, MCT4, and GPR81 were higher in the STW-H and DYD groups than those in the model group.
CONCLUSIONS
STW can reduce the pregnancy loss rate by regulating the glycolysis balance at the maternal-fetal interface of kidney deficiency threatened abortion model mice.
Topics: Pregnancy; Humans; Mice; Female; Animals; Abortion, Threatened; Mifepristone; Hydrocortisone; Abortion, Spontaneous; Abortion, Induced
PubMed: 37068718
DOI: 10.1016/j.jep.2023.116502 -
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 -
American Journal of Public Health Oct 1992
Topics: Clinical Protocols; Consumer Advocacy; Humans; Internationality; Mifepristone; Politics; Pregnant Women; Risk Assessment; Social Control, Formal
PubMed: 1415852
DOI: 10.2105/ajph.82.10.1325 -
JNMA; Journal of the Nepal Medical... 2018During the last decade, medical methods for second trimester abortion have considerably improved and become safe and more accessible. The combination of mifepristone and... (Comparative Study)
Comparative Study
INTRODUCTION
During the last decade, medical methods for second trimester abortion have considerably improved and become safe and more accessible. The combination of mifepristone and misoprostol is now an established and highly effective method for second trimester abortion. But where mifepristone is not available or affordable, misoprostol alone has also been shown to be effective. The objective of this study is to compare the efficacy of mifepristone with misoprostol and misoprostol alone for second trimester termination of pregnancy.
METHODS
It is a comparative study conducted on 60 patients from 13 to 18 weeks of gestation admitted for second trimester termination on legal indications.
RESULTS
Mean induction abortion interval was comparable in both the groups. Of the 30 cases in each group, nine cases in each Group A and six cases in Group B had incomplete/failed expulsion. Among these 15 cases, only nine required check curettage for complete evacuation while others received oxytocics only for completion. The distribution of these cases was also comparable in both the groups. Only one patient in Group B had complete failure of expulsion and underwent surgical evacuation. However, the difference in dosage of misoprostol required for complete expulsion and incidence of side effects were significantly higher in the group B.
CONCLUSIONS
Mifepristone and misoprostol combined together is now an established, highly effective and safe method for medical method of second trimester termination. However, when mifepristone is not available or affordable, misoprostol alone can also be used effectively, although a higher total dose is needed and side effects are higher than with the combined regimen.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Legal; Adult; Dilatation and Curettage; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, Second; Treatment Failure; Young Adult
PubMed: 31065120
DOI: 10.31729/jnma.3690 -
BMJ (Clinical Research Ed.) Apr 2003
Topics: Adult; Clinical Trials as Topic; Contraceptives, Postcoital, Hormonal; Female; Health Services Accessibility; Humans; Levonorgestrel; Mifepristone; Risk Factors; Sexually Transmitted Diseases; Time Factors
PubMed: 12689951
DOI: 10.1136/bmj.326.7393.775 -
The Cochrane Database of Systematic... Jan 2016Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been positively linked with symptom severity in people with psychosis. Antiglucocorticoid and related drugs that target the HPA axis may be useful for the treatment of individuals with psychosis.
OBJECTIVES
1. To determine the effects of antiglucocorticoid and related drugs for the treatment of psychosis, when used alone or in combination with antipsychotic medication.2. To determine whether the effects of these medications differs between those in a prodromal phase or first episode of psychosis, and those with more established illness.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (August 2009 and April 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing antiglucocorticoid and related drugs compared to placebo (either as a sole treatment or as an adjunct to atypical antipsychotics, typical antipsychotics, antidepressants or other combination treatment) for people with a primary diagnosis of a psychotic disorder, or for individuals at high risk of developing a psychotic disorder.
DATA COLLECTION AND ANALYSIS
Review authors independently selected trials, assessed methodological quality and extracted data. We used a fixed-effect meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and standardised mean differences (SMDs) with 95% CIs for continuous measures. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table.
MAIN RESULTS
We included 11 studies that randomly assigned 509 people with schizophrenia, schizoaffective disorder or psychotic depression. No trials were conducted in patients at their first episode of psychotic illness and none included populations at high risk for developing psychosis. Our pre-stated outcomes of interest were mental state, global state, general functioning, adverse effects and quality of life.Two trials compared antiglucocorticoid drugs (mifepristone) versus placebo as sole treatment. Limited data from one trial showed no difference in the proportion responding to mifepristone when mental state was assessed immediately post intervention using the Brief Psychiatric Rating Scale (BPRS) (n = 5, 1 RCT, MD -5.20, 95% CI -17.91 to 7.51; very low-quality evidence); depressive symptoms (Hamilton Rating Scale for Depression (HAMD) total) were also similar between groups (n = 5, 1 RCT, MD 1.67, 95% CI -16.44 to 19.78; very low-quality evidence). However, a significant difference favoured treatment at short-term follow-up for global state (30% reduction in total BPRS, n = 221, 1 RCT, RR 0.58, 95% CI 0.38 to 0.89; low-grade quality evidence). This effect was also seen for short-term positive psychotic symptoms (50% reduction in BPRS positive symptom subscale, n = 221, 1 RCT, RR 0.60, 95% CI 0.43 to 0.84; low-grade quality evidence). Participants receiving mifepristone experienced a similar overall number of adverse effects as those receiving placebo (n = 226, 2 RCTs, RR 0.92, 95% CI 0.77 to 1.09; moderate-quality evidence). No data on general functioning or quality of life were available.One trial compared an antiglucocorticoid, dehydroepiandrosterone (DHEA), as an adjunct to atypical antipsychotic treatment to adjunctive placebo. Data for main outcomes of interest were of low quality, and analysis of useable data showed no significant effects of treatment on mental state or adverse effects. Data on global state, general functioning and quality of life were not available.Data from six trials comparing antiglucocorticoid drugs as an adjunct to combination treatment versus adjunctive placebo showed no significant differences between groups in mean endpoint scores for overall psychotic symptoms (n = 171, 6 RCTs, SMD 0.01, 95% CI - 0.29 to 0.32) or positive psychotic symptoms (n = 151, 5 RCTs, SMD -0.07, 95% CI - 0.40 to 0.25). Data from three trials showed no differences between groups in mean endpoint scores for negative symptoms (n = 94, 3 RCTs, MD 2.21, 95% CI -0.14 to 4.55). One study found improvements in global state that were similar between groups (n = 30, 1 RCT, RR 0.58, 95% CI 0.32 to 1.06; very low-quality evidence). In this comparison, pooled results showed that antiglucorticoids caused a greater overall number of adverse events (n = 199, 7 RCTs, RR 2.66, 95% CI 1.33 to 5.32; moderate quality evidence), but no quality of life data were available.
AUTHORS' CONCLUSIONS
Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis. Some global state findings suggest a favourable effect for mifepristone, and a few overall adverse effect findings favour placebo. Additional large randomised controlled trials are needed to justify findings.
Topics: Dehydroepiandrosterone; Dexamethasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Ketoconazole; Mifepristone; Pituitary-Adrenal System; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 26725721
DOI: 10.1002/14651858.CD006995.pub2 -
BMC Psychiatry May 2023Major depressive disorder (MDD) is a heterogeneous psychiatric disorder. Childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18) is one of...
BACKGROUND
Major depressive disorder (MDD) is a heterogeneous psychiatric disorder. Childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18) is one of the largest and most consistent risk factors for development and poor course of MDD. Overactivity of the HPA-axis and the stress hormone cortisol is thought to play a role in the vulnerability for MDD following exposure to CT. Rodent experiments showed that antagonism of the glucocorticoid receptor (GR) at adult age reversed the effects of early life stress. Similarly, we aim to target MDD in individuals with CT exposure using the GR antagonist mifepristone.
METHODS
The RESET-medication study is a placebo-controlled double-blind randomized controlled trial (RCT) which aims to include 158 adults with MDD and CT. Participants will be randomized (1:1) to a 7-day treatment arm of mifepristone (1200 mg/day) or a control arm (placebo). Participants are allowed to receive usual care for MDD including antidepressants. Measurements include three face-to-face meetings at baseline (T0), day 8 (T1), week 6 (T2), and two online follow-up meetings at 12 weeks (T3) and 6 months (T4). A subgroup of participants (N = 80) are included in a fMRI sub-study (T0, T2). The main study outcome will be depressive symptom severity as measured with the Inventory of Depressive Symptomatology-Self Rated (IDS-SR) at T2. Secondary outcomes include, among others, depressive symptom severity at other time points, disability, anxiety, sleep and subjective stress. To address underlying mechanisms mifepristone plasma levels, cortisol, inflammation, epigenetic regulation and fMRI measurements are obtained.
DISCUSSION
The RESET-medication study will provide clinical evidence whether GR antagonism is a disease-modifying treatment for MDD in individuals exposed to CT. If effective, this hypothesis-driven approach may extend to other psychiatric disorders where CT plays an important role.
TRIAL REGISTRATION
The trial protocol has been registered 01-02-2022 on ClinicalTrials.gov with ID "NCT05217758".
Topics: Humans; Adverse Childhood Experiences; Depressive Disorder, Major; Hydrocortisone; Mifepristone; Randomized Controlled Trials as Topic; Receptors, Glucocorticoid; Treatment Outcome; Adult
PubMed: 37170109
DOI: 10.1186/s12888-023-04830-9 -
BMJ Open Oct 2022Pharmacists were acknowledged as the most appropriate healthcare professional to dispense mifepristone for medication abortion shortly after the prescription therapy...
INTRODUCTION
Pharmacists were acknowledged as the most appropriate healthcare professional to dispense mifepristone for medication abortion shortly after the prescription therapy became available in January 2017 in Canada.
OBJECTIVE
We aimed to identify the facilitators and barriers for successful initiation and ongoing dispensing of mifepristone among community pharmacists across Canada.
STUDY DESIGN
We surveyed community pharmacists from urban/rural practice settings across Canada by recruiting from January 2017 to January 2019 through pharmacist organisations, professional networks, at mifepristone training courses and at professional conferences. The Diffusion of Innovations theory informed the study design, thematic analysis and interpretation of findings. We summarised categorical data using counts and proportions, χ tests, Wilcoxon rank-sum and proportional odds logistic regression.
RESULTS
Of the 433 responses from dispensing community pharmacists across 10/13 Canadian provinces and territories, 93.1% indicated they were willing and ready to dispense mifepristone. Key facilitators were access to a private consultation setting (91.4%), the motivation to increase accessibility for patients (87.5%) and to reduce pressure on the healthcare system (75.3%). The cost of the mifepristone/misoprostol product was an initial barrier, subsequently resolved by universal government subsidy. A few pharmacists mentioned liability, lack of prescribers or inadequate stock as barriers.
CONCLUSIONS
Pharmacist respondents from across Canada reported being able and willing to dispense mifepristone and rarely mentioned barriers to stocking/dispensing the medication in the community pharmacy setting. The removal of initial regulatory obstacles to directly dispense mifepristone to patients facilitated the provision of medication abortion in the primary care setting.
Topics: Abortion, Induced; Canada; Female; Humans; Mifepristone; Misoprostol; Pharmacists; Pregnancy; Surveys and Questionnaires
PubMed: 36207038
DOI: 10.1136/bmjopen-2022-063370 -
International Journal of Environmental... Jul 2022Mifepristone (RU-486) has been approved for abortion in Taiwan since 2000. Mifepristone was the first non-addictive medicine to be classified as a schedule IV controlled...
BACKGROUND
Mifepristone (RU-486) has been approved for abortion in Taiwan since 2000. Mifepristone was the first non-addictive medicine to be classified as a schedule IV controlled drug. As a case of the "misuse" of "misuse of drugs laws," the policy and consequences of mifepristone-assisted abortion for pregnant women could be compared with those of illicit drug use for drug addicts.
METHODS
The rule-making process of mifepristone regulation was analyzed from various aspects of legitimacy, social stigma, women's human rights, and access to health care.
RESULTS AND DISCUSSION
The restriction policy on mifepristone regulation in Taiwan has raised concerns over the legitimacy of listing a non-addictive substance as a controlled drug, which may produce stigma and negatively affect women's reproductive and privacy rights. Such a restriction policy and social stigma may lead to the unwillingness of pregnant women to utilize safe abortion services. Under the threat of the COVID-19 pandemic, the US FDA's action on mifepristone prescription and dispensing reminds us it is time to consider a change of policy.
CONCLUSIONS
Listing mifepristone as a controlled drug could impede the acceptability and accessibility of safe mifepristone use and violates women's right to health care.
Topics: Abortion, Induced; COVID-19; Female; Humans; Mifepristone; Pandemics; Pregnancy; Public Policy; Women's Health; COVID-19 Drug Treatment
PubMed: 35886217
DOI: 10.3390/ijerph19148363 -
The Journals of Gerontology. Series A,... Feb 2017The Drosophila GeneSwitch system facilitates the spatial and temporal control of gene expression through dietary supplementation of mifepristone (RU486). Because...
The Drosophila GeneSwitch system facilitates the spatial and temporal control of gene expression through dietary supplementation of mifepristone (RU486). Because experimental and control groups differ only by treatment with RU486, confounding results from using flies of different genetic backgrounds are eliminated, making GeneSwitch especially useful in studies of aging. However, the effect of RU486 itself on longevity has not been well characterized, particularly in relation to nutritional states known to affect lifespan. Here, we show that RU486 has dose- and diet-dependent effects on longevity in both sexes. On low nutrient diets, RU486 supplementation reduces total food consumption, perhaps exacerbating undernutrition to shorten life. RU486 also inhibits proboscis extension responses to low nutrient diets, suggesting that RU486 has an aversive taste which leads to decreased food consumption and diminished longevity. RU486 is not detrimental to fly lifespan on high nutrient food, correlating with reduced effects of the drug on palatability and total consumption on rich diets. Our results highlight the critical importance of considering how food palatability and nutrient intake might be altered by dietary or drug manipulations in studies of aging and behavior.
Topics: Animals; Drosophila; Feeding Behavior; Female; Food Preferences; Longevity; Male; Mifepristone
PubMed: 27093874
DOI: 10.1093/gerona/glw072