The World Health Organization includes oral emergency contraception (EC) in the list of essential medicines. Ulipristal acetate (UPA) and levonorgestrel (LNG) are the recommended oral methods. UPA has superior efficacy and a comparable side effect profile compared with LNG. Both work by inhibiting or delaying ovulation, so that sperm present in the reproductive tract will have lost their fertilising ability by the time the oocyte is eventually released. Neither LNG nor UPA at the EC doses have significant effects on the endometrium and are unable to prevent implantation. Mifepristone can also be used for EC but its availability is limited to few countries. LNG is less effective in women with a body mass index over 26 kg/m2 or weight over 70 kg. Hormonal contraception can be quickstarted immediately following LNG, or five days following UPA. LNG-releasing intrauterine devices and cyclo-oxygenase inhibitors are promising options for EC to be further studied.

暂无摘要。

Cryopreservation of porcine spermatozoa is detrimental due to their high sensitivity to cold shock, leading to changes akin to capacitation, known as cryocapacitation. These changes, including the acrosomal reaction, hypermotility induction, and protein phosphorylation, might be influenced by the presence of progesterone in seminal plasma and egg yolk, used in most freezing extenders. We tested the effect of various progesterone concentrations added to the freezing extenders (1, 10, and 100 μg/mL). At 100 μg/mL, progesterone decreased the proportion of straightness and tended to reduce viability and the proportion of progressive motility (p < 0.1). At 10 μg/mL, it increased reacted acrosomes in dead sperm (p < 0.05), protein phosphorylation rate (p < 0.05), and tended (p < 0.1) to enhance linear movement compared to the control. To counteract the capacitating effect of progesterone, we examined the effect of antiprogesterone mifepristone (RU 486) at concentrations of 5, 10, 20, 50, 100, and 200 μM, and co-incubated 10 μM of RU 486 with 10 μg/mL of progesterone. RU 486 maintained capacitation levels and motility parameters similar to the control, although high concentrations (100 μM) tended (p = 0.152) to increase protein phosphorylation. Co-incubation reduced the acrosome reaction in dead sperm, and RU 486 appeared to prevent hypermotility stabilizing motility and viability parameters compared to samples with progesterone alone. Protein phosphorylation increased and RU 486 could not restore capacitation to control levels due to its competitive antagonism for progesterone receptors, having less affinity than progesterone, which displaces RU 486 at high concentrations, allowing normal sperm capacitation.

Miscarriage and abortion require similar clinical management. Restrictions placed on abortion threaten the quality of miscarriage care, a policy spillover that affects many Americans. We combined vital statistics with life-table parameters to estimate that 1,034,000 miscarriages occur annually, including nearly 400,000 in US states with abortion bans. Attempts to restrict mifepristone access further threaten miscarriage management.

BACKGROUND: Medical abortion after 12 gestational weeks often requires a stay in hospital. We hypothesised that administering the first misoprostol dose at home could increase day-care procedures as compared with overnight care procedures, shorten inpatient stays, and improve patient satisfaction.
METHODS: This multicentre, open-label, randomised controlled trial was done at six hospitals in Sweden. Participants were pregnant people aged 18 years and older who were undergoing medical abortion at 85-153 days of pregnancy. Randomisation was done in blocks 1:1 to mifepristone administered in-clinic followed by home administration or hospital administration of the first dose of misoprostol. Allocation was done by opening of opaque allocation envelopes. Due to the nature of the intervention, masking was not feasible. Between 24-48 h after mifepristone 200 mg, the participants administered 800 μg of misoprostol either at home 2 h before admission to hospital or in hospital. The primary outcome was the proportion of day-care procedures (defined as abortion completed in <9 h). The intention-to-treat analysis included all participants randomly assigned to receive the study drug and who had known results for the primary outcome. Individuals who received any treatment were included in the safety analyses. This trial is registered at ClinicalTrials.gov, NTC03600857, and EudraCT, 2018-000964-27.
RESULTS: Between Jan 8, 2019, and Dec 21, 2022, 457 participants were randomly assigned to treatment groups. In the intention-to-treat-population, 220 participants were assigned to the home group and 215 to the hospital group. In the home group, 156 (71%) of 220 participants completed the abortion as day-care patients, compared with 99 (46%) of 215 in the hospital group (difference 24·9%, 95% CI 15·4-34·3; p<0·0001). In total, 97 (22%) of 444 participants in the safety analysis had an adverse event. Seven (2%) of 444 participants aborted after mifepristone only. Two (1%) of 220 in the home group aborted after the first dose of misoprostol, before hospital admission.
CONCLUSIONS: Home administration of misoprostol significantly increases the proportion of day-care procedures in medical abortion after 12 gestational weeks, offering a safe and effective alternative to in-clinic protocols.
BACKGROUND: Region Västra Götaland, Hjalmar Svensson\'s Fund, the Gothenburg Society of Medicine, Karolinska Institutet-Region Stockholm, and The Swedish Research Council.

暂无摘要。

BACKGROUND: Stress is one of the most common precipitating factors in migraine and is identified as a trigger in nearly 70% of patients. Responses to stress include release of glucocorticoids as an adaptive mechanism, but this may also contribute to migraine attacks. Here, we investigated the role of glucocorticoids on stress-induced migraine-like behaviors.
METHODS: We have shown previously that repeated stress in mice evokes migraine-like behavioral responses and priming to a nitric oxide donor. Metyrapone, mifepristone, and corticosterone (CORT) were used to investigate whether CORT contributes to the stress-induced effects. Facial mechanical hypersensitivity was evaluated by von Frey testing and grimace scoring assessed the presence of non-evoked pain. We also measured serum CORT levels in control, stress, and daily CORT injected groups of both male and female mice.
RESULTS: Metyrapone blocked stress-induced responses and priming in male and female mice. However, repeated CORT injections in the absence of stress only led to migraine-like behaviors in females. Both female and male mice showed similar patterns of serum CORT in response to stress or exogenous administration. Finally, administration of mifepristone, the glucocorticoid receptor antagonist, prior to each stress session blocked stress-induced behavioral responses in male and female mice.
CONCLUSIONS: These findings demonstrate that while CORT synthesis and receptor activation is necessary for the behavioral responses triggered by repeated stress, it is only sufficient in females. Better understanding of how glucocorticoids contribute to migraine may lead to new therapeutic opportunities.

OBJECTIVE: To compare medication abortion (MAB) success in very early pregnancy (VEP) with mifepristone followed by either one or two doses of misoprostol.
METHODS: We performed a retrospective cohort analysis of VEP MABs from 7/1/2021 to 05/31/2022 treated with mifepristone 200mg oral followed by a single dose of misoprostol 800mcg buccal 24-48 hours later and MABs from 06/21/2022 to 10/31/2022 treated with mifepristone 200mg oral followed by two doses of misoprostol 800mcg buccal spaced four hours apart, with first dose taken 24-48 hours after mifepristone. Serum BhCG was collected at the time of mifepristone treatment with additional BhCG collected 48-72 hours after misoprostol treatment in both groups. Success was defined as a BhCG decline of > or = 50%. MAB failure was defined as ongoing, viable pregnancy determined by follow up ultrasound or procedural intervention with aspiration.
RESULTS: There were 423 patients in the single dose misoprostol group and 262 patients in the two-dose misoprostol group. There were no significant differences between the two groups in baseline characteristics. In the single dose group, 372 (87.9%) were treated successfully; in the two-dose group, 224 (85.5%) were treated successfully. There was no significant difference in MAB success between the groups (p=0.73).
CONCLUSIONS: The addition of a second dose of misoprostol does not improve the success of MAB in VEP.
BACKGROUND: N/A.

Background Second-trimester abortions, constitute 10-15% of global annual abortions, leading to two-thirds of major abortion-related complications. Recognizing the elevated risk, the WHO recommends diverse methods for safe termination. Surgical and medical approaches, particularly using drugs like Mifepristone and Misoprostol, show promising success rates. Objective To analyze the outcomes of second-trimester termination using Mifepristone or PG analogues alone or in combination. Method This is a one-year retrospective study at Tribhuvan University Teaching Hospital analyzing second-trimester terminations, collecting data on demographics, medical history, period of gestation, doses of abotificient drugs, complications, and management. Result In a study of 66 second-trimester abortions, mean age was 28.8±4.96 years, gestational age 20.07±4.3 weeks. Mifepristone and Misoprostol combination succeeded in 66.7% of cases, while 42.2% required repeated Mifepristone doses. Misoprostol use was significantly higher in patients without medical comorbidities (p=0.018), but Mifepristone requirement didn\'t differ significantly based on medical conditions. Combined Mifepristone and Misoprostol were used more for fetal indications. Notably, the use of Mifepristone and Misoprostol didn\'t significantly differ for live and intrauterine fetal death cases. Conclusion Mifepristone and Misoprostol effectively terminate second-trimester pregnancies. In high-risk cases, cautious Prostaglandin use is crucial and Mifepristone alone, in divided doses, reduces complications with high success.

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.