Search

Telehealth abortion has become critical to addressing surges in demand in states where abortion remains legal but evidence on its effectiveness and safety is limited. California Home Abortion by Telehealth (CHAT) is a prospective study that follows pregnant people who obtained medication abortion via telehealth from three virtual clinics operating in 20 states and Washington, DC between April 2021 and January 2022. Individuals were screened using a standardized no-test protocol, primarily relying on their medical history to assess medical eligibility. We assessed effectiveness, defined as complete abortion after 200 mg mifepristone and 1,600 μg misoprostol (or lower) without additional intervention; safety was measured by the absence of serious adverse events. We estimated rates using multivariable logistic regression and multiple imputation to account for missing data. Among 6,034 abortions, 97.7% (95% confidence interval (CI) = 97.2-98.1%) were complete without subsequent known intervention or ongoing pregnancy after the initial treatment. Overall, 99.8% (99.6-99.9%) of abortions were not followed by serious adverse events. In total, 0.25% of patients experienced a serious abortion-related adverse event, 0.16% were treated for an ectopic pregnancy and 1.3% abortions were followed by emergency department visits. There were no differences in effectiveness or safety between synchronous and asynchronous models of care. Telehealth medication abortion is effective, safe and comparable to published rates of in-person medication abortion care.

Purpose: This meta-analysis aimed to comprehensively assess the teratogenic risk to offspring associated with continuing pregnancy after administering mifepristone and/or misoprostol during gestation. Methods: We conducted a systematic search of multiple databases, including PubMed, Web of Science, Embase, Cochrane, CNKI, and CBM, from their inception to February 2024, with no language restrictions. We included cohort and case–control studies that analyzed the teratogenic effects of mifepristone and/or misoprostol on fetuses and newborns. Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). The odds ratios (OR) from individual studies were combined using meta-analysis. Sensitivity testing and heterogeneity analysis were conducted. Results: A total of 13 studies were eligible for inclusion, comprising 5193 cases of congenital malformations and 12,232 controls. Conclusion: Our findings indicated that the use of misoprostol during early pregnancy increased the risk of congenital abnormalities in offspring (OR = 2.69; 95% CI: 1.57–4.62). However, the potential teratogenic effect of mifepristone during pregnancy cannot be ruled out. Additionally, the use of mifepristone and/or misoprostol has been linked to a higher risk of certain congenital anomalies, such as hydrocephalus (OR = 3.41; 95% CI: 1.17–9.97), Möbius syndrome (OR = 26.48; 95% CI: 11.30–62.01), and terminal transverse limb defects (OR = 10.75; 95% CI: 3.93–29.41). (PROSPERO, CRD42024522093, 03182024). [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of iron-dependent cell death that has attracted significant attention for its potential role in numerous diseases. Targeted inhibition of ferroptosis could be of potential use in treating diseases: such as drug induced liver injury (DILI). Ferroptosis can be antagonized by the xCT/GSH/GPX4, FSP1/CoQ 10 , DHODH/CoQ 10 , GCH1/BH 4 , and NRF2 pathways. Identifying novel anti-ferroptosis pathways will further promote our understanding of the biological nature of ferroptosis and help discover new drugs targeting ferroptosis related human diseases. In this study, we identified the clinically used drug mifepristone (RU486) as a novel ferroptosis inhibitor. Mechanistically, RU486 inhibits ferroptosis by inducing GSH synthesis pathway, which supplies GSH for glutathione-S-transferase (GST) mediated 4-HNE detoxification. Furthermore, RU486 induced RLIP76 and MRP1 export 4-HNE conjugate contributes to its anti-ferroptosis activity. Interestingly, RU486 induced GSH/GSTs/RLIP76&MRP1 anti-ferroptosis pathway acts independent of classic anti-ferroptosis systems: including xCT/GSH/GPX4, FSP1, DHODH, GCH1, SCD1 and FTH1. Moreover, NRF2 was identified to be important for RU486's anti-ferroptosis activity by inducing downstream gene expression. Importantly, in mouse model, RU486 showed strong protection effect on acetaminophen (APAP)-induced acute liver injury, evidenced by decreased ALT, AST level and histological recovery after APAP treatment. Interestingly, RU486 also decreased oxidative markers, including 4-HNE and MDA, and induced NRF2 activation as well as GSTs, MRP1 expression. Together, these data suggest NRF2/GSH/GST/RLIP76&MRP1 mediated detoxification pathway as an important independent anti-ferroptosis pathway act both in vitro and in vivo. • Mifepristone is a novel ferroptosis inhibitor that independent of the major pathways. • Mifepristone (RU486) promotes 4-HNE detoxification to antagonize ferroptosis. • RU486 increases GSH and upregulates GST activity to promote detoxification of 4-HNE. • RU486 boosts export of 4-HNE conjugate by activating NRF2, enhancing RLIP76 and MRP1. • RU486 shields the liver from APAP injury, echoing in vitro mechanisms. [ABSTRACT FROM AUTHOR]

Copyright of Gynäkologische Endokrinologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AbstractPurposeMaterials and methodsResultsConclusions\nSHORT CONDENSATIONAnnually, approximately 31,000 people experience a termination of pregnancy (TOP) in the Netherlands. In 2021, about one-third of them chose medical termination of pregnancy (MTOP). We explored experiences with MTOP and to what extent expectations, pain, and counselling in the clinic are associated with satisfaction with MTOP.A retrospective cross-sectional study was conducted using an online questionnaire. We included 138 respondents, ≥16 years, who chose MTOP (September 2020–March 2022).The majority of respondents experienced MTOP more positively than expected or as expected (67%). For 24%, the experience was more negative than expected. In the event of another TOP, half of these respondents would hesitate to choose or would not choose MTOP, mainly due to physical side effects. The majority of respondents (73%) would choose MTOP again. Their main motivation was self-determination during treatment. Respondents cited four key elements: pain, intensity of experience during and after treatment, blood loss, and duration. Correspondence between MTOP expectations and experiences was associated with satisfaction with MTOP, while pain and satisfaction with counselling were not.The majority of respondents were satisfied with MTOP and would choose the treatment again. Non-correspondence between expectations and experiences negatively affected satisfaction with MTOP. This highlights the importance of managing expectations by providing accessible information about the variety in expectations and experiences to patients with a focus on key elements of the experience.The majority experienced the abortion pill more positively than expected or as expected. Four experience elements are key: pain, intensity during and after treatment, blood loss, duration. Information about these elements is crucial since non-correspondence of expectation and experience negatively affects satisfaction. [ABSTRACT FROM AUTHOR]

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial–mesenchymal transition (EMT) markers. [ABSTRACT FROM AUTHOR]

Christian pro-lifers often respond to Thomson's defense of abortion that the violinist is allowed to die while the embryo is killed. Boonin and McMahan counter that this distinction does not provide an objection to extraction abortions that disconnect embryos and allow them to die. I disagree. I first argue that letting die and killing are not to be distinguished by differences between acts and omissions, moral and immoral motives, intentional or unintentional deaths, and causing or not causing a pathology. I offer a taxonomy in which hysterotomies turn out to be killings. I then argue that if either the placenta is considered an organ of the embryo or the embryo is construed as a part of the pregnant woman, then abortion pills kill rather than allow death. So, assuming that killing people is morally worse than letting them die, extraction abortions can be condemned to the same degree as other abortions. [ABSTRACT FROM AUTHOR]

This study examines abortion-related discourse on Twitter (X) pre-and post-Dobbs v. Jackson ruling, which eliminated the constitutional right to abortion. We used a custom data collection tool to collect tweets directly from Twitter using abortion-related keywords. We used the BERTopic language model and examined the top 30 retweeted and top 30 textually similar tweets from relevant topic clusters using an inductive coding approach. We also conducted statistical testing to assess potential associations between abortion themes. 166,799 unique tweets were collected from December 2020-December 2022. 464 unique tweets were coded for abortion-related themes with 154 identified as relevant. Of these, 66 tweets marketed abortion pills, 17 tweets were identified as offering consultations, and 91 tweets were relevant to self-managed abortion. All marketing and consultation tweets were posted post-Dobbs decision and 7 (7.69%) of self-managed tweets were posted pre-Dobbs versus 84 (92.30%) posted post-Dobbs. A positive association was found between tweets offering a medical consultation with tweets marketing abortion pills and discussing self-managed abortion. This study detected online marketing of abortion pills, consultations and discussions about self-managed abortion following the Dobbs v. Jackson ruling. These results provide more context to the type of abortion-related information that is available online. This study examined tweets occurring both pre and post Dobbs decision and identified relevant discussions about self-managed abortion services, marketing and sale of abortion pills, and offering purported medical consultations. These findings indicate that abortion-related tweets, particularly those marketing abortion medications, increased after the Dobbs v. Jackson ruling. These findings highlight the evolving abortion information environment in the United States on Twitter, which represents a platform where health and politicised issues are commonly discussed. [ABSTRACT FROM AUTHOR]

Objectives: The objective of our study was to identify and characterize barriers to mifepristone use among obstetrician-gynecologists (OB-GYNs) for early pregnancy loss in a southern US state. Methods: In this qualitative study, we conducted semistructured interviews with 19 OB-GYNs in Alabama who manage early pregnancy loss. The interviews explored participants' knowledge of and experience with mifepristone use for miscarriage management and abortion, along with barriers to and facilitators of clinical mifepristone use. The interviews were coded by multiple study staff using inductive and deductive thematic coding. Results: Nearly all of the interviewees identified abortion-related stigma as a barrier to mifepristone use. Interviewees often attributed stigma to a lack of knowledge about the clinical use of mifepristone for early pregnancy loss. The stigmatization of mifepristone due to its association with abortion was related to religious and political objections. Many interviewees also described stigma associated with misoprostol use. Although providers believed that mifepristone use for abortion would not be accepted in their practice, most believed that mifepristone could be used successfully for miscarriage management after practice-wide education on its use. Conclusions: Mifepristone is strongly associated with abortion stigma among OB-GYNs in Alabama, which is a barrier to its use for miscarriage management. Interventions to decrease abortion stigma and associated stigma surrounding mifepristone are needed to optimize early pregnancy loss care. [ABSTRACT FROM AUTHOR]

Progesterone receptor antagonism is gaining attention due to progesterone's recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial and examines changes in breast mRNA expression following mifepristone treatment in healthy premenopausal women. We analyzed 32 paired breast biopsies from 16 women at baseline and after two months of mifepristone treatment. In total, 27 differentially expressed genes were identified, with enriched biological functions related to extracellular matrix remodeling. Notably, the altered gene signature induced by mifepristone in vivo was rather similar to the in vitro signature. Furthermore, this gene expression signature was linked to breast carcinogenesis and notably linked with progesterone receptor expression status in breast cancer, as validated in The Cancer Genome Atlas dataset using the R2 platform. The present study is the first to explore the breast transcriptome following mifepristone treatment in normal breast tissue in vivo, enhancing the understanding of progesterone receptor antagonism and its potential protective effect against breast cancer. [ABSTRACT FROM AUTHOR]

The pathophysiology of many mood disorders is closely related to abnormal stress response associated with the dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and cortisol overproduction. The hippocampus, a key structure of the limbic system responsible for both cognitive and emotional spheres, is selectively vulnerable to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration. The antiGC therapy of psychiatric diseases, in particular depressive disorders, may be a useful additional treatment. Among other approaches, targeting glucocorticoid receptors, abounded in the hippocampus, is regarded as highly promising. However, though the preclinical data provide fairly firm evidence to the concept of antiGC therapy for stress-related diseases, clinical studies still are at the proof-of-concept stage. Noteworthy, chronic GC excess is associated not only with mood diseases, but also with cognitive decline, metabolic disorders, diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate affective symptoms, cognitive disturbances, GC and insulin resistance and adverse side effects of conventional drugs through beneficial effects on the hippocampus mitigating its dysfunction and neurodegeneration, neuroinflammation, and impairment of neurogenesis. Since stress/GC-associated neuroinflammation-mediated pathology of the limbic system and, specifically, the hippocampus, is a general feature typical for many brain diseases, the concept of antiGC therapy may be extended, tested and validated in a wider spectrum of cerebral pathologies. [ABSTRACT FROM AUTHOR]

Background Glucocorticoids are the treatment of choice for proteinuric patients with minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS). Immunosuppressive as well as direct effects on podocytes are believed to mediate their actions. In this study, we analyzed the anti-proteinuric effects of inhibition of the glucocorticoid receptor (GR) in glomerular epithelial cells, including podocytes. Methods We employed genetic and pharmacological approaches to inhibit the GR. Genetically, we used Pax8-Cre/GRfl/fl mice to specifically inactivate the GR in kidney epithelial cells. Pharmacologically, we utilized a glucocorticoid antagonist called mifepristone. Results Genetic inactivation of GR, specifically in kidney epithelial cells, using Pax8-Cre/GRfl/fl mice, ameliorated proteinuria following protein overload. We further tested the effects of pharmacological GR inhibition in three models and species: the puromycin aminonucleoside–induced nephrosis model in rats, the protein overload model in mice and the inducible transgenic NTR/MTZ zebrafish larvae with specific and reversible podocyte injury. In all three models, both pharmacological GR activation and inhibition consistently and significantly ameliorated proteinuria. Additionally, we translated our findings to humans, where three nephrotic adult patients with MCD or primary FSGS with contraindications or insufficient responses to corticosteroids were treated with mifepristone. This treatment resulted in a clinically relevant reduction of proteinuria. Conclusions Thus, across multiple species and proteinuria models, both genetic and pharmacological GR inhibition was at least as effective as pronounced GR activation. While the mechanism remains perplexing, GR inhibition may be a novel and targeted therapeutic approach to treat glomerular proteinuria potentially bypassing adverse actions of steroids. [ABSTRACT FROM AUTHOR]

Mating in female Drosophila melanogaster causes midgut hypertrophy and reduced lifespan, and these effects are blocked by the drug mifepristone. Eip75B is a transcription factor previously reported to have pleiotropic effects on Drosophila lifespan. Because Eip75B null mutations are lethal, conditional systems and/or partial knock-down are needed to study Eip75B effects in adults. Previous studies showed that Eip75B is required for adult midgut cell proliferation in response to mating. To test the possible role of Eip75B in mediating the lifespan effects of mating and mifepristone, a tripartite FLP-recombinase-based conditional system was employed that provides controls for genetic background. Expression of a Hsp70-FLP transgene was induced in third instar larvae by a brief heat pulse. The FLP recombinase catalyzed the recombination and activation of an Actin5C-GAL4 transgene. The GAL4 transcription factor in turn activated expression of a UAS-Eip75B-RNAi transgene. Inhibition of Eip75B activity was confirmed by loss of midgut hypertrophy upon mating, and the lifespan effects of both mating and mifepristone were eliminated. In addition, the negative effects of mifepristone on egg production were eliminated. The data indicate that Eip75B mediates the effects of mating and mifepristone on female midgut hypertrophy, egg production, and lifespan. [ABSTRACT FROM AUTHOR]

No abstract

ObjectivesTo assess access to abortion pills offered by clinics providing state-funded family planning services in California.MethodsWe attempted to make two scripted calls to a 20% random sample of family planning clinics in California, stratified by county, as "secret shoppers" in 2020 and 2021.ResultsClinic staff responded to 407 calls. Only 50 respondents (12%) reported their clinic offered abortion pills and 23 respondents (6%) accurately indicated to callers that abortion pills were available free to low-income individuals in California. Most (68%) clinics that did not offer abortion pills could not direct callers to a clinic that did offer abortion pills.ConclusionsEfforts are needed to increase the number of clinics providing medication abortion services in California. Clinic staff need training to provide accurate information about medication abortion.

Context: Aims: This study aims to compare the effectiveness, induction to abortion interval, blood loss, and side effect profile between administration of intraamniotic prostaglandin F2 alpha (PGF2α) with a combination of mifepristone and misoprostol for medical termination of pregnancy in mid-trimester. Prospective observational study. Subjects and Methods: The study was conducted by dividing the women with indicated mid-trimester abortions into two groups of 20 women each. Group-I received Tablet Mifepristone 200 mg orally on day 1 and then after 48 h, Tablet Misoprostol 400 μg given per vaginally every 4 h till abortion was completed or a maximum of 5 doses whichever was earlier. Group-II received a single injection of PGF2α (250 μg) intra-amniotically under ultrasonography guidance. Group comparisons were made using t-test/Mann–Whitney U-test for normally/nonnormally distributed continuous data, respectively, and Chi-square test for categorical variables. SPSS version 23 was used for analysis. P < 0.05 was taken as the cut-off for statistical significance. Results: The success rate was 100% in both the groups. There was a significant difference in the mean induction to abortion interval between Group-I, the mean being 12.92 ± 2.68 h compared to Group-II being 33.08 ± 6.35 h (P < 0.001). Group-I had a mean blood loss of 221 ± 55.15 mL, significantly more than Group-II 160 ± 25.13 mL (P < 0.001). Twenty-five percent of the Group-I woman had retained products of conception with none in Group-II (P = 0.029). The pain score was better in Group II (pain score 4.4 vs. 5.7, P < 0.001). Fewer women developed chills in Group II compared to Group I (0% vs. 50%, P < 0.001). Conclusions: PGF2α is equally effective as a combination of Mifepristone and Misoprostol in mid-trimester abortion. Although it has a longer induction to abortion interval, it appears to be better with respect to the completeness of evacuation, lesser blood loss, and better patient tolerance.

ObjectivesThis study aimed to review clinical practice outcomes of early pregnancy loss (EPL) medical management using mifepristone and misoprostol outside of a clinical trial setting.Study designIn this retrospective cohort study, we reviewed a deidentified database of patients who received mifepristone-misoprostol for EPL from May 2018 to May 2021 at our academic center-based clinic, which was a study site for a multicenter mifepristone-misoprostol EPL trial completed in March 2018. All patients received mifepristone 200 mg orally and misoprostol 800 mcg vaginally or buccally, with clinic follow-up typically scheduled within 1 week. The primary outcome was successful medical management, defined as management without the need for aspiration, and the secondary outcomes included additional interventions and indications, follow-up ultrasonography findings, and adverse events requiring treatment.ResultsWe treated 90 patients with a median ultrasound-measured gestational size of 49 (range 30-80) days and median time from mifepristone to misoprostol of 24 (range 8-66) hours. Follow-up was completed in clinic by 80 (88.9%), completed remotely by five (5.6%), and not completed by five (5.6%) patients. Overall, 76 (95% CI 82.9%-96.0%) of 85 patients (89.4%) with follow-up were successfully managed without uterine aspiration. Eighty patients had initial follow-up ultrasonography interpreted as gestational sac expulsion; seven (8.8%) of these ultimately underwent aspiration, including one patient who had a previously undiagnosed cesarean scar ectopic pregnancy. Two patients had significant safety outcomes: one pelvic infection and one blood transfusion during aspiration in the patient with a cesarean scar ectopic pregnancy.ConclusionsOutside of a clinical trial setting, medical management of EPL with mifepristone and misoprostol remains effective and safe.ImplicationsMedical management of EPL with mifepristone and misoprostol is effective and safe outside of a clinical trial setting. A standardized protocol based on the best available clinical trial evidence can be used in clinical practice for the medical management of EPL.

Abstract Background Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region is limited. Methods A standardized assessment tool measuring access to Mifepristone, Misoprostol, and contraceptive medicines included in the WHO essential medicines list (EML) was implemented in eight countries in the Eastern Mediterranean Region (Afghanistan, Iraq, Lebanon, Libya, Morocco, Palestine, Pakistan, and Somalia) between 2020–2021. The assessment focused on five access measures: 1) the inclusion of medicines in national family planning guidelines; 2) inclusion of medicines in comprehensive abortion care guidelines; 3) inclusion of medicines on national essential medicines lists; 4) medicines registration; and 5) procurement and forecasting of Mifepristone, Misoprostol, and contraceptive medicines. A descriptive analysis of findings from these eight national assessments was conducted. Results Only Lebanon and Pakistan included all 12 contraceptives that are enlisted in the WHO-EML within their national family planning guidelines. Only Afghanistan and Lebanon included mifepristone and mifepristone-misoprostol combination in post-abortion care guidelines, but these medicines were not included in their national EMLs. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs—and registered—in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan). However, only three countries procured misoprostol (Iraq, Morocco, and Somalia). Conclusion These findings can guide efforts aimed at improving the availability of Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region. Opportunities include expanding national EMLs to include more options for Mifepristone, Misoprostol, and contraceptive medicines and strengthening the registration and procurement systems to ensure these medicines’ availability were permitted under national law and where culturally acceptable.

Abstract Background Medical abortion with mifepristone and misoprostol can be provided up to 63 days’ gestation in India. This accounts for 67.5 percent of all abortions in the country. We conducted an assessment to determine the availability of medical abortion medicines, specifically the combi-pack, in India. Methods We applied the World Health Organization landscape assessment protocol at the national level. The assessment protocol included a five-step adaptation of an existing availability framework, including online data collection, desk review, country-level key informant interviews, and an analysis to identify barriers and opportunities to improve medical abortion availability. The assessment was conducted between August and March 2021. Results Medicines for medical abortion are included in the national essential drug list and available with prescription in India. The assessment identified 42 combi-pack products developed by 35 manufacturers. The quality of medical abortion medicines is regulated by national authorities; but as health is devolved to states, there are significant inter-state variations. This is seen across financing, procurement, manufacturing, and monitoring mechanisms for quality assurance of medical abortion medicines prior to distribution. There is a need to strengthen supply chain systems, ensure consistent availability of trained providers and build community awareness on use of medical abortion medicines for early abortions, at the time of the assessment. Conclusion Opportunities to improve availability and quality of medical abortion medicines exist. For example, uniform implementation of regulatory standards, greater emphasis on quality-assurance during manufacturing, and standardizing of procurement and supply chain systems across states. Regular in-service training of providers on medical abortion is required. Finally, innovations in evidence dissemination and community engagement about the recently amended abortion law are needed.

Cushing′s syndrome (CS), an endocrine disorder resulting from excessive glucocorticoid secretion by the adrenal cortex, poses significant challenges to both diagnosis and treatment. The diagnostic process involves comprehensive evaluation, combining laboratory tests and imaging studies for screening, qualification, and localization. Surgical intervention remains the primary treatment approach, although pharmacological therapy also plays a crucial role. With an increasing understanding of the pathogenesis of CS, more potential targets for orphan drug development have been discovered. This article summarizes the current status of diagnosis and treatment for CS and provides an outlook on future research directions.

Background: Medical abortion with mifepristone and misoprostol can be provided up to 63 days' gestation in India. This accounts for 67.5 percent of all abortions in the country. We conducted an assessment to determine the availability of medical abortion medicines, specifically the combi-pack, in India. Methods: We applied the World Health Organization landscape assessment protocol at the national level. The assessment protocol included a five-step adaptation of an existing availability framework, including online data collection, desk review, country-level key informant interviews, and an analysis to identify barriers and opportunities to improve medical abortion availability. The assessment was conducted between August and March 2021. Results: Medicines for medical abortion are included in the national essential drug list and available with prescription in India. The assessment identified 42 combi-pack products developed by 35 manufacturers. The quality of medical abortion medicines is regulated by national authorities; but as health is devolved to states, there are significant inter-state variations. This is seen across financing, procurement, manufacturing, and monitoring mechanisms for quality assurance of medical abortion medicines prior to distribution. There is a need to strengthen supply chain systems, ensure consistent availability of trained providers and build community awareness on use of medical abortion medicines for early abortions, at the time of the assessment. Conclusion: Opportunities to improve availability and quality of medical abortion medicines exist. For example, uniform implementation of regulatory standards, greater emphasis on quality-assurance during manufacturing, and standardizing of procurement and supply chain systems across states. Regular in-service training of providers on medical abortion is required. Finally, innovations in evidence dissemination and community engagement about the recently amended abortion law are needed. Plain language summary: Medical abortion is popular in India and benefits from a liberal legal context. It is important to understand the availability of quality abortion medicines in the country. Using the World Health Organization country assessment protocol and availability framework for medical abortion medicines we examined the availability of these medicines from supply to demand. We used this information to identify opportunities for increasing availability of quality-assured medical abortion medicines. We found that the context for medical abortion varies across states. Strengthening procurement and supply chain management, with a greater emphasis on quality-assurance and regulation of manufacturing should be instituted at the state-level. Training is also needed to increase provider knowledge of the latest national guidelines and laws to ensure respectful and person-centered services. Finally, the public should be informed about medical abortion as a safe and effective choice, especially for early abortions. [ABSTRACT FROM AUTHOR]

Research Summary Policy Implications The U.S. Supreme Court's Dobbs decision overturning Roe v. Wade has profound implications for the 58,000 incarcerated women who are pregnant. Especially in states that now ban abortion, women in prisons and jails who prefer to terminate their pregnancy will be denied that choice by the government and will be forced to give birth. Based on a July 2023 YouGov survey (N = 800) employing three experiments and measuring attitudes toward inmate abortion and parental aid, the current study examines public opinion on coerced motherhood, focusing on states prohibiting reproductive choice. The results reveal that a majority of the American public favors providing incarcerated women in these states with access to abortion through surgical procedures or medication (pills). Among respondents residing in states banning abortion, more endorse than oppose reproductive rights. Support for abortion is particularly high when the pregnancy is due to rape or poses a risk to a woman's health. Respondents also approve incarcerated mothers receiving parental aid (e.g., baby food, baby clothing, nursery care). Notably, conservative Republicans are most in favor of coercing motherhood and least in favor of providing parental aid.Coerced motherhood behind bars is a human rights violation. Our study shows that it is also opposed by the American public. Thus, ideological space exists for reforms aimed at providing incarcerated women with access to reproductive services. Every correctional facility should be given a written protocol (Model Reproductive Services Code) that mandates pregnancy screenings, counseling, and assistance in scheduling services, as well as transportation for surgery and/or access to pills for a medical abortion. Above all, transparency is needed to raise consciousness about coerced motherhood behind bars and to shed light on how corrections professionals handle inmate pregnancies. [ABSTRACT FROM AUTHOR]

Background: Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region is limited. Methods: A standardized assessment tool measuring access to Mifepristone, Misoprostol, and contraceptive medicines included in the WHO essential medicines list (EML) was implemented in eight countries in the Eastern Mediterranean Region (Afghanistan, Iraq, Lebanon, Libya, Morocco, Palestine, Pakistan, and Somalia) between 2020–2021. The assessment focused on five access measures: 1) the inclusion of medicines in national family planning guidelines; 2) inclusion of medicines in comprehensive abortion care guidelines; 3) inclusion of medicines on national essential medicines lists; 4) medicines registration; and 5) procurement and forecasting of Mifepristone, Misoprostol, and contraceptive medicines. A descriptive analysis of findings from these eight national assessments was conducted. Results: Only Lebanon and Pakistan included all 12 contraceptives that are enlisted in the WHO-EML within their national family planning guidelines. Only Afghanistan and Lebanon included mifepristone and mifepristone-misoprostol combination in post-abortion care guidelines, but these medicines were not included in their national EMLs. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs—and registered—in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan). However, only three countries procured misoprostol (Iraq, Morocco, and Somalia). Conclusion: These findings can guide efforts aimed at improving the availability of Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region. Opportunities include expanding national EMLs to include more options for Mifepristone, Misoprostol, and contraceptive medicines and strengthening the registration and procurement systems to ensure these medicines' availability were permitted under national law and where culturally acceptable. Plain English summary: Ensuring access to Mifepristone, Misoprostol, and contraceptive medicines is critical to improving women's health, and more specifically reducing maternal mortality and improving women's sexual and reproductive health in the Eastern Mediterranean Region. The aim of this study was to analyse findings from national assessments to capture information on the implementation of relevant policies and procedures. Those were the policies that ensure access to Mifepristone, Misoprostol, and contraceptive medicines in the public sector for the eight Eastern Mediterranean Region countries included in the study (Afghanistan, Iraq, Libya, Lebanon, Morocco, Palestine, Pakistan, and Somalia). The assessments were completed between 2020 and 2021. We found that most countries did not include all twelve contraceptives enlisted in the WHO essential medicines list (EML) in their national family planning guidelines. No country had developed a national abortion care guidelines nor included mifepristone (alone or in combination with misoprostol) on national EML. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs—and registered—in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan) yet, only three countries procured misoprostol (Iraq, Morocco, and Somalia). Our findings provide evidence on system-level barriers to availability of Mifepristone, Misoprostol, and contraceptive medicines (e.g., lack of guidelines or inclusion on EML, lack of registration and procurement) that can support policy and advocacy efforts to strengthen the pharmaceutical sector to better ensure availability of Mifepristone, Misoprostol, and contraceptive medicines to women in reproductive age at the country-level in accordance with the national law and prevailing culture. [ABSTRACT FROM AUTHOR]

The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF-α and IL-1β) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1β expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF-α expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF-α expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF-α and IL-1β), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1β), pre-frontal cortex (IL-1β), and hypothalamus (IL-1β). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss. [ABSTRACT FROM AUTHOR]

Background: Modern-day obstetrics recommend induction of labor by medical or mechanical methods where continuation of pregnancy causes detrimental effect to the health of mother or fetus. One of the prerequisites for successful vaginal delivery includes a favorable or ripe cervix. We undertook the present study to find out the safety and efficacy of mifepristone for pre-induction cervical ripening and its effect on Bishop's score in term pregnancy. Methods: A total of 100 patients with term pregnancy were enrolled for this study. 200 mg of mifepristone was administered orally, and efficacy of mifepristone was assessed based on improvement in modified Bishop's score at 48 h. If there was inadequate improvement in Bishop's score after 48 h, additional intracervical cerviprime was administered for induction. Results: Out of 100 patients, 50 women delivered vaginally after administration of mifepristone. Twenty-four patients delivered vaginally within 48 h of administration of mifepristone. We observed the Bishop's score of 6 or more at 48 h in 69% participants. Fifty patients required additional intracervical cerviprime. Thirty participants underwent cesarean section. Mean Modified Bishop's score at 0 h was 1.87 and improved to 6.92 after 48 h after mifepristone. A statistically significant difference was found with mean Bishop's score with p value < 0.005. Conclusion: In our study, we found that mifepristone is a safe and effective cervical ripening agent in term pregnancy with unfavorable cervix. It is well tolerated and leads to significant cervical ripening with improvement in Bishop's score favoring vaginal delivery. [ABSTRACT FROM AUTHOR]

Background and Study Objective: Uterine leiomyomas, or fibroids, are prevalent benign gynecological tumors affecting many women during their reproductive years. While surgical excision has long been the gold standard for fibroid treatment, the pharmacological management, including progesterone receptor modulators like mifepristone (RU 486), has garnered attention due to the reduced surgical approaches. However, there is a notable paucity of research on the effectiveness of mifepristone, on the same. This study seeks to evaluate the safety and efficacy of mifepristone in reducing uterine leiomyoma size and alleviating associated symptoms. Methodology: Conducted prospectively, the study enrolled 20 pre-menopausal women, aged 18 years or older, from Nanavati Max Super Speciality Hospital Mumbai, Maharashtra, India. Participants were selected based on specific inclusion criteria, including the presence of at least one uterine myoma with a minimum diameter of 2.5 cm as confirmed by ultrasound. Participants had an average age of 39.75 years and an average BMI of 27.58 kg/m2. Results: The study found that mifepristone significantly reduced uterine volume by 75%, with hemoglobin levels substantially improving from 9 gm/dL initially to 12.51 gm/dL after six months. Pain intensity, assessed using the Visual Analog Scale (VAS) score, gradually decreased from baseline to three-month, with all 20 patients reporting the complete absence of pelvic pain by six months. Conclusion: This prospective study highlights mifepristone's promise as a non-surgical approach to effectively reduce uterine fibroid volume, improve hemoglobin levels, and mitigate uterine blood loss in patients. [ABSTRACT FROM AUTHOR]

This report presents a case of unilateral pyometra in an 8-year-old intact female cat, focusing on clinical observations, pathological findings, diagnostic techniques, surgical intervention, and outcomes. [ABSTRACT FROM AUTHOR]

After the legalization of abortion in 2018, Ireland needed clinicians to become abortion providers and make this political win a medical reality. Yet Irish doctors had next‐to‐no training in abortion care, and barriers ranging from stigma to economic pressures in the healthcare system impacted doctors' desire to volunteer. How did hundreds of Irish doctors make the shift from family doctor to abortion provider? Drawing on ethnographic research conducted between 2017 and 2020, this article explores the process by which Irish general practitioners became abortion providers, attending to the material impact of medical technologies on that journey. Drawing from medical anthropologists who have examined similar themes of agency, pharmaceuticals, and medico‐legal frameworks within the topic of assisted dying, I build on Anita Hannig's idea of "agentive displacement" to frame the productive impact of abortion pills on this transition. [ABSTRACT FROM AUTHOR]

Background: In 2019, the World Health Organization identified improving access to safe abortion as an important priority toward improving sexual and reproductive health and rights and achieving Sustainable Development Goals. One strategy for addressing this priority is strengthening access to medicines for medical abortion. All 11 countries in the South-East Asia Region have some indications for legal abortion and permit post-abortion care. Therefore, strengthening access to medical abortion medicines is a reasonable strategy for improving access to safe abortion for the Region. Methodology: We applied an adapted version of an existing World Health Organization landscape assessment protocol for the availability of medical abortion medicines at the country-level in the South-East Asia Region. We collected publicly available data on the existence of national health laws, policies, and standard treatment guidelines; inclusion of medical abortion medicines in the national essential medicines list; and marketing authorization status for medical abortion medicines for each country and verified by Ministries of health. The findings were once more presented, discussed and recommendations were formulated during regional technical consultation workshop. Each country teams participated in the process, and subsequently, the suggestions were validated by representatives from Ministries of Health.. Results: Few countries in the Region currently have national policies and guidelines for comprehensive safe abortion. However, either mifepristone-misoprostol in combination or misoprostol alone (for other indications) is included in national essential medicines lists in all countries except Indonesia and Sri Lanka. Few countries earmark specific public funds for procuring and distributing medical abortion commodities. In countries where abortion is legal, the private sector and NGOs support access to medical abortion information and medicines. Several countries only allow registered medical practitioners or specialists to administer medical abortion. Conclusion: Following this rapid participatory assessment and technical consultation workshop, the World Health Organization South-East Asia Regional Technical Advisory and Sexual and Reproductive Health and Rights technical committee recommended priority actions for policy and advocacy, service delivery, and monitoring and evaluation, and indicated areas for support. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoid (GR) and mineralocorticoid (MR) receptors are highly expressed in cardiac tissue, and both can be activated by corticosteroids. MR activation, in acute myocardial infarction (AMI), worsens cardiac function, and increase NHE activity contributing to the deleterious process. In contrast, effects of GR activation are not fully understood, probably because of the controversial scenario generated by using different doses or potencies of corticosteroids. Aims: We tested the hypothesis that an acute dose of hydrocortisone (HC), a low‐potency glucocorticoid, in a murine model of AMI could be cardioprotective by regulating NHE1 activity, leading to a decrease in oxidative stress. Materials and Methods: Isolated hearts from Wistar rats were subjected to regional ischemic protocol. HC (10 nmol/L) was added to the perfusate during early reperfusion. Infarct size and oxidative stress were determined. Isolated papillary muscles from non‐infarcted hearts were used to evaluate HC effect on sodium‐proton exchanger 1 (NHE1) by analysing intracellular pH recovery from acute transient acidosis. Results: HC treatment decreased infarct size, improved cardiac mechanics, reduced oxidative stress after AMI, while restoring the decreased level of the pro‐fusion mitochondrial protein MFN‐2. Co‐treatment with the GR‐blocker Mifepristone avoided these effects. HC reduced NHE1 activity by increasing the NHE1 pro‐inhibiting Ser648 phosphorylation site and its upstream kinase AKT. HC restored the decreased AKT phosphorylation and anti‐apoptotic BCL‐2 protein expression detected after AMI. Conclusions: Our results provide the first evidence that acute HC treatment during early reperfusion induces cardioprotection against AMI, associated with a non‐genomic HC‐triggered NHE1 inhibition by AKT and antioxidant action that might involves mitochondrial dynamics improvement. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have demonstrated quality concerns with misoprostol. Mifepristone, however, has not been extensively assessed for quality. Between 2020 and 2021, Concept Foundation and the International Planned Parenthood Federation conducted a study to determine the quality of these medical abortion drugs in low‐ and middle‐income countries (LMIC). Methods: The collection of batch samples of misoprostol and mifepristone was carried out by trained sampling agents in selected LMIC. Single drug packs and combipacks were sampled. A World Health Organization prequalified laboratory conducted testing method verifications and subsequent sample analysis. Tests included identification, assay, related substances, and content uniformity for misoprostol, and identification, assay, related substances, and dissolution for mifepristone. Results: Samples were collected from Burkina Faso, Cambodia, Democratic Republic of Congo, India, Kyrgyzstan, Moldova, Nepal, Nigeria, Pakistan, Uganda and Vietnam. Sixty‐four pooled batch samples were tested, consisting of 31 combipacks, 26 misoprostol‐only and seven mifepristone‐only products. Overall, 54.7% of samples were non‐compliant with one or more of the specifications, representing 51.6% of combipack products, 57.1% of misoprostol tablets analyzed and 23.7% of mifepristone tablets. One falsified misoprostol‐only product was found. Conclusion: The present study confirms that a significant problem still exists in relation to the quality of medical abortion drugs in LMIC. For misoprostol, our findings suggest that historical concerns around primary packaging may have been largely resolved but that manufacturing processes for both finished product and active pharmaceutical ingredient need to be improved. The present study also provides evidence of mifepristone quality issues. Synopsis: Over half of mifepristone, misoprostol, and combipack samples collected and tested did not meet one or more requirements. One product was falsified. [ABSTRACT FROM AUTHOR]

Introduction: Unsafe abortions account for about 5% maternal deaths in India. A very small proportion of induced abortions takes place at registered facilities, and many women prefer taking abortion pills as a method of contraception. The current study was planned to explore the factors related to use of abortion pills and knowledge about various contraceptives among slum-dwelling women. Materials and Methods: A community-based cross-sectional study was carried out in the urban slum area catered by a public health dispensary for 2 months among 22 females. Data collection was performed using a semistructured interview schedule for quantitative data, and focused group discussion (FGD) was performed for qualitative data collection. Thematic data analysis was performed for FGD. Themes pertaining to knowledge, ease of use, and source and side effects of abortion pills, knowledge, use, and fears/myths for modern contraceptive methods were identified. Results: A total of 35 unwanted pregnancies were reported by 22 women study participants, out of which only three were continued. Most study participants came to know about abortion pills from their neighborhood friends or maternal relatives such as sisters, and 90% of them preferred either chemists or local private practitioners for getting abortion pills. Fears and myths for modern contraceptive methods, their non-regular supply, and easy availability of abortion pills were the main reason for their use. Conclusion: The study highlights women's perspective of using abortion pills over modern contraceptive methods as a method to limit their family size or for spacing and highlights the lack of family planning counseling. Such a situation calls for enhanced counseling services for modern contraceptive methods and health promotion programs to alleviate fears about contraceptive methods. [ABSTRACT FROM AUTHOR]