Mifepristone

BackgroundTo evaluate the feasibility of conducting a prospective study to measure self-managed medication abortion outcomes, and to collect preliminary data on safety and effectiveness of self-managed medication abortion, we recruited callers to accompaniment groups (volunteer networks that provide counselling through the out-of-clinic medication abortion process by trained counselors over the phone or in-person).MethodsIn 2019, we enrolled callers to three abortion accompaniment groups in three countries into a prospective study on the safety and effectiveness of self-managed medication abortion with accompaniment support. Participants completed up to five interview-administered questionnaires from baseline through 6-weeks after taking the pills. Primary outcomes included: (1) the number of participants enrolled in a 30-day period, (2) the proportion that had a complete abortion; and (3) the proportion who experienced any warning signs of potential or actual complications.ResultsOver the 30-day recruitment period, we enrolled 227 participants (95% of those invited), and retained 204 participants (90%) for at least one study follow-up visit. At the 1-week follow-up, two participants (1%) reported a miscarriage prior to taking the pills, and 202 participants (89% of those enrolled and 99% of those who participated in the 1-week survey) had obtained and taken the medications. Three weeks after taking the medications, 192 (95%) participants reported feeling that their abortion was complete. Three (1.5%) received a surgical intervention, two (1%) received antibiotics, and five (3%) received other medications. Participants did not report any major adverse events.ConclusionThese results establish the feasibility of conducting prospective studies of self-managed medication abortion in legally restrictive settings. Further, the high effectiveness of self-managed medication abortion with accompaniment support reported here is consistent with high levels of effectiveness reported in prior studies. Trial registration ISRCTN95769543.

BackgroundChronic stress or prolonged administration of glucocorticoids suppresses proliferation and/or survival of newborn cells in adult rat dentate gyrus. Earlier we showed that administration of the glucocorticoid receptor antagonist mifepristone during the final 4 days of a 21 days period of corticosterone treatment fully normalized the number of newborn cells. Here we aimed to better understand how mifepristone achieves this effect and questioned whether an even shorter (single day) mifepristone treatment (instead of 4 days) also suffices to normalize neurogenesis.MethodsWe investigated various steps of the neurogenic process, using the immunohistochemical markers BrdU, doublecortin, proliferating cell nuclear antigen as well as glial fibrillary acidic protein, after 17 or 21 days of corticosterone (versus vehicle) treatment.ResultsCorticosterone primarily attenuates the proliferation of cells which subsequently develop into neurons; this is fully reversed by mifepristone. Surprisingly, the corticosteroid effects on neurogenesis can even be fully re-set by a single-day treatment with mifepristone (on day 18), despite the continued corticosterone exposure on subsequent days.ConclusionsOur results emphasize that studies into the therapeutical efficacy of new antidepressants, especially those targeting HPA-activity or the glucocorticoid receptor, should explore the possibility to reduce treatment duration.

Early life adversity is a well-known risk factor for behavioral dysfunction later in life, including the formation of contextual memory; it is also (transiently) accompanied by hyperactivity of the stress system. We tested whether mifepristone (MIF) treatment, which among other things blocks glucocorticoid receptors (GRs), during the prepubertal period [postnatal days (PND)26-PND28] normalizes memory deficits in adult male rats exposed to 24-h maternal deprivation (MD) at PND3. MD reduced body weight gain and increased basal corticosterone (CORT) levels during the PND26, but not in adulthood. In adulthood, contextual memory formation of MD compared to noMD (i.e., control) male rats was significantly impaired. This impairment was fully prevented by MIF treatment at PND26-PND28, whereas MIF by itself did not affect behavior. A second behavioral test, a rodent version of the Iowa Gambling Task (rIGT), revealed that flexible spatial learning rather than reward-based aspects of performance was impaired by MD; the deficit was prevented by MIF. Neuronal activity as tested by c-Fos staining in the latter task revealed changes in the right hippocampal-dorsomedial striatal pathway, but not in prefrontal areas involved in reward learning. Follow-up electrophysiological recordings measuring spontaneous glutamate transmission showed reduced frequency of miniature postsynaptic excitatory currents in adult CA1 dorsal hippocampal and enhanced frequency in dorsomedial striatal neurons from MD versus noMD rats, which was not seen in MIF-treated rats. We conclude that transient prepubertal MIF treatment normalizes hippocampus-striatal-dependent contextual memory/spatial learning deficits in male rats exposed to early life adversity, possibly by normalizing glutamatergic transmission.

ImportanceFollowing decades-long declines, significant increases in abortion rates have been reported in some jurisdictions from 2020 to 2023, but it is not yet known whether these trends are occurring in Canada.ObjectiveTo assess abortion rates in Ontario from 2012 to 2022 and to examine trend changes associated with mifepristone availability, the COVID-19 pandemic, and postpandemic periods.Design, setting, and participantsThis population-based interrupted time series cohort study examined all medication and procedural abortions provided in Ontario from January 1, 2012, to December 31, 2022, to females aged 15 to 44 years with provincial insurance coverage, identified using linked health administrative data that included records from practitioner billings, inpatient and outpatient hospital services, same-day surgeries, and outpatient prescription dispensations.ExposureAvailability of mifepristone regulated as a normal (ie, prescribed by an authorized prescriber without additional certification or registration and dispensed by a pharmacist) prescription medication (in November 2017) and the COVID-19 pandemic period (from March 2020 to December 2021).Main outcomes and measuresThe main outcome was the abortion rate (number of abortions per 1000 females per year) overall and within age strata, using an interrupted time series design.ResultsOf 422 867 medication and procedural abortions identified using data from health records of 225 540 reproductive-aged females (mean [SD] age, 28.5 [6.6] years), the abortion rate declined steadily from 15.6 abortions per year per 1000 females, aged 15 to 44 years, in 2012 to 12.3 in 2021 and then increased to 14.1 in 2022. When mifepristone was introduced in 2017 as a normal prescription medication, no immediate change in the abortion rate (-0.1 [95% CI, -0.7 to 0.8]) and a nonsignificant slope increase (0.6 [95% CI, -0.5 to 0.7]) were found. However, this trend resulted in an additional 1.5 (95% CI, 0.3-2.6) abortions per 1000 females by the first quarter of 2020 compared with premifepristone trends; rates increased more among those aged 15 to 19 years, less among those aged 35 to 44 years, and did not increase for those aged 25 to 29 years. During the pandemic period, abortion rates decreased by 1.2 (95% CI, -2.5 to -0.8), most pronounced among those aged 20 to 34 years. Compared with expected rates based on premifepristone trends, 5-year availability of normally prescribed mifepristone was associated with a rate difference of 1.9 (95% CI, 0.7-5.4) in 2022, with a greater increase among those aged 20 to 24 years (4.2 [95% CI, 1.5-9.0]) and no change among those aged 25 to 29 years (1.0 [95% CI, -1.7 to 6.2]). The increased abortion rate in 2022 was consistent with 5-year trends following normally prescribed mifepristone, although social forces potentially impacting international rates may have contributed.Conclusions and relevanceThis study found that, following longstanding declines, abortion rates in Ontario gradually increased with mifepristone availability in 2017 in Ontario. Following a pandemic-related decrease in rates (in 2020 and 2021), substantial increases in abortion rates reported elsewhere from 2020 to 2023 did not occur in Ontario as of 2022, suggesting that Ontario's health services environment and Canada's regulatory and policy approach to preserving reproductive health services may have helped stabilize abortion rates. Future research is needed to understand how sociocultural changes affecting abortion service use elsewhere may be affecting contraception access and use and thus abortion rates in Canada.