-
Addiction Biology Jul 2023Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross-over,... (Randomized Controlled Trial)
Randomized Controlled Trial
Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1-week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue-reactivity procedure and alcohol self-administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue-induced saliva output. During the alcohol self-administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild-moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress-induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone-induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non-treatment seekers and suggests future treatment-oriented trials should investigate mifepristone in people with AUD.
Topics: Humans; Craving; Mifepristone; Hydrocortisone; Alcoholism; Alcohol Drinking; Ethanol; Double-Blind Method
PubMed: 37369125
DOI: 10.1111/adb.13288 -
Journal of Clinical Medicine Sep 2023Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments... (Review)
Review
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.
PubMed: 37834773
DOI: 10.3390/jcm12196130 -
JAMA Network Open Oct 2023Misoprostol-alone regimens for abortion may be more effective than previously thought. (Observational Study)
Observational Study
IMPORTANCE
Misoprostol-alone regimens for abortion may be more effective than previously thought.
OBJECTIVE
To estimate the effectiveness of medication abortion with misoprostol alone among individuals self-managing their abortion.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective observational cohort study of callers to safe abortion hotlines and accompaniment groups in Argentina, Nigeria, and Southeast Asia, participants were recruited between July 31, 2019, and October 1, 2020, prior to starting their medication abortion. Eligible participants were 13 years or older, had no contraindications to medication abortion, and were not currently bleeding. Participants completed a baseline and 2 follow-up surveys. The analysis was restricted to participants who reported using misoprostol alone and was performed between January 6, 2022 and September 8, 2023.
EXPOSURE
Self-managed medication abortion using misoprostol alone.
MAIN OUTCOMES AND MEASURES
The primary outcome was effectiveness, defined as participant self-report of complete abortion without procedural intervention, measured at 1 week and 3 weeks after taking misoprostol. Secondary outcomes included method safety, measured by self-report of experiencing warning signs (eg, heavy bleeding, pain, fever, discharge) indicative of a potential complication and by medical treatment (eg, blood transfusion, intravenous fluids, overnight hospital stay) indicative of a potential adverse event. Additional outcomes included length of bleeding and cramping, time to expulsion, and experience of adverse effects.
RESULTS
Among 1352 enrolled participants, 637 used misoprostol-alone regimens for abortion and were included in the analysis (591 [92.8%] from Nigeria, 45 [7.1%] from Southeast Asia, and 1 [0.2%] from Argentina; 384 [60.2%] aged 20-29 years; 317 [49.8%] with pregnancy durations <7 weeks and 205 [32.2%] with pregnancy durations between 7 and <9 weeks). At last follow-up after taking medication (median, 22 days; IQR, 21-26 days), 625 participants (98.1%; 95% CI, 96.7%-98.9%) had a complete abortion without procedural intervention. Potential adverse events were reported by 6 participants (0.9%; 95% CI, 0.4%-2.1%). Most participants experienced bleeding for less than 1 week (median, 4 days; IQR, 3-6 days) and expelled their pregnancy within 24 hours of starting the abortion process (median, 12 hours; IQR, 9-15 hours). Common side effects included nausea (335 participants [52.6%]), fever (232 [36.4%]), and diarrhea (181 [28.4%]).
CONCLUSIONS AND RELEVANCE
The findings suggest that misoprostol alone is a highly effective method of pregnancy termination. Future research should explore strategies to maximize the effectiveness of misoprostol alone in clinical and nonclinical settings.
Topics: Pregnancy; Female; Humans; Misoprostol; Prospective Studies; Mifepristone; Abortion, Induced; Abortion, Spontaneous
PubMed: 37889485
DOI: 10.1001/jamanetworkopen.2023.40042 -
Obstetrical & Gynecological Survey Jan 2024Several medications have been used to achieve medical abortion in the first trimester of pregnancy. The most commonly used is the combination of mifepristone and... (Review)
Review
IMPORTANCE
Several medications have been used to achieve medical abortion in the first trimester of pregnancy. The most commonly used is the combination of mifepristone and misoprostol; however, different doses and routes of administration have been proposed.
OBJECTIVE
The aim of this study was to summarize published data on the effectiveness, adverse effects, and acceptability of the various combinations of mifepristone and misoprostol in medical abortion protocols in the first trimester of pregnancy.
EVIDENCE ACQUISITION
This was a comprehensive review, synthesizing the findings of the literature on the current use of mifepristone and misoprostol for first-trimester abortion.
RESULTS
The combination of mifepristone and misoprostol seems to be more effective than misoprostol alone. Regarding the dosages and routes, mifepristone is administered orally, and the optimal dose is 200 mg. The route of administration of misoprostol varies; the sublingual and buccal routes are more effective; however, the vaginal route (800 μg) is associated with fewer adverse effects. Finally, the acceptability rates did not differ significantly.
CONCLUSIONS
Different schemes for first-trimester medical abortion have been described so far. Future research needs to focus on identifying the method that offers the best trade-off between efficacy and safety in first-trimester medical abortion.
Topics: Pregnancy; Female; Humans; Mifepristone; Misoprostol; Pregnancy Trimester, First; Abortion, Induced; Abortifacient Agents, Nonsteroidal
PubMed: 38306292
DOI: 10.1097/OGX.0000000000001222 -
Contraception May 2024To evaluate the availability of mifepristone and misoprostol at pharmacies in a state with protective abortion legislation and variation in access by rurality.
OBJECTIVES
To evaluate the availability of mifepristone and misoprostol at pharmacies in a state with protective abortion legislation and variation in access by rurality.
STUDY DESIGN
Using a secret shopper survey, researchers attempted to contact all community pharmacies in Oregon and evaluate their mifepristone and misoprostol provisions.
RESULTS
Among the 444 pharmacies surveyed, mifepristone was planned at 19.2%. Misoprostol was available at 77.5%, but stocking issues and medication ordering impact access, without significant differences by rurality.
CONCLUSIONS
Pharmacy engagement and support are key to increasing access to these essential medicines, which may be improved through education and referral programs.
PubMed: 38763275
DOI: 10.1016/j.contraception.2024.110491 -
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 -
Diseases (Basel, Switzerland) Nov 2023Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational... (Review)
Review
Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the , and genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases and are expected to be effective only for the prevention of the occurrence of -dependent nodules.
PubMed: 37987267
DOI: 10.3390/diseases11040156 -
Contraception May 2024In January 2023, the Food & Drug Administration modified the Risk Evaluation and Mitigation Strategy program regulating mifepristone to allow direct dispensation from...
In January 2023, the Food & Drug Administration modified the Risk Evaluation and Mitigation Strategy program regulating mifepristone to allow direct dispensation from retail pharmacies. In June 2023, we conducted a random, distributive survey of pharmacies in California using secret shopper methodology to investigate the feasibility of accessing mifepristone. One pharmacy had mifepristone immediately available (<24 hours), and misoprostol availability was limited. Accessibility to misoprostol varied by type of pharmacy (p < 0.01), but not by region. Even in a reproductive freedom state, access to mifepristone and misoprostol from outpatient retail pharmacies remains limited.
PubMed: 38806139
DOI: 10.1016/j.contraception.2024.110506 -
Journal of Clinical Medicine Nov 2023Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a... (Review)
Review
Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a maternal mortality rate of 2-2.5%. Implantation happens in the proximal portion of the fallopian tube as it passes through the myometrium. The resolution of interstitial pregnancy after medical treatment should be assessed by a decline in serum β-hCG, which occurs in about 85-90% of cases. Nonetheless, its effectiveness and consequences have been presented through case reports and case series. However, few cases of interstitial pregnancies treated totally medically with the use of methotrexate and mifepristone have been presented in the literature. Complications of this medical treatments have also never been reviewed before. In the present manuscript, we present a case of interstitial pregnancy treated with methotrexate and mifepristone. The patient after treatment developed a uterine arteriovenous malformation, treated with uterine artery embolization. Furthermore, we performed a systematic review of the literature using Scopus, PubMed and Google Scholar. A total of 186 papers were found, and 7 papers which included 10 cases were assessed for eligibility. The systemic medical treatment with the use of methotrexate and mifepristone was effective in 7 of the 10 cases. Two cases of hemoperitoneum following combined methotrexate and mifepristone treatment were reported. The applicability of this medical conservative treatment should be tailored to the patient, taking into account their obstetric history, gestational age at diagnosis and desire for future pregnancies. Complete resolution after this treatment was achieved in most of the cases reported without major complications. The appearance of uterine arteriovenous malformation can be managed conservatively, and we propose uterine artery embolization as an effective treatment of this rare complication.
PubMed: 38068448
DOI: 10.3390/jcm12237396 -
The European Journal of Contraception &... Oct 2023To explore women's perception of the need for an ultrasound scan before medical abortion provided by telemedicine services.
PURPOSE
To explore women's perception of the need for an ultrasound scan before medical abortion provided by telemedicine services.
METHODS
We have analysed women's requests for medical abortion through the website www.womenonweb.org from the 1st of January 2019 to the 5th of October 2020. Before receiving abortion drugs for self-managed medical abortion, women received online counselling and were asked to complete an online survey on pre-abortion ultrasound scan and the reasons for having or not having one. The initial dataset included 62641 entries from 207 countries. Each entry corresponded to a person's request for medical abortion. Women reported only one or multiple reasons for not having a pre-abortion ultrasound scan.
RESULTS
Among 59648 women requesting a medical abortion, 45653 (76,54%) did not have any pre-abortion ultrasound scan and specified a reason for that. The countries with the highest rates of women not having a pre-abortion ultrasound scan were Thailand, Poland, Northern Ireland, Mexico, South Korea, Japan, Chile, Indonesia, Germany, and Brazil. The main reasons for not having a pre-abortion ultrasound scan were being confident regarding pregnancy length; and thus, no need for a scan stated by 10910/34390 women (31.7%), lack of resources stated by 10589/34390 women (30.8%), and privacy issues stated by 6472/34390 women (18.8%).
CONCLUSION
Most women opting for medical abortion through telemedicine did not undergo a pre-abortion ultrasound scan. The main reason stated was that women did not find it necessary, lack of resources and privacy issues.
Topics: Pregnancy; Female; Humans; Mifepristone; Misoprostol; Abortion, Induced; Northern Ireland; Surveys and Questionnaires
PubMed: 37698511
DOI: 10.1080/13625187.2023.2249158