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Frontiers in Pharmacology 2023Progesterone has been shown to have neuroprotective capabilities against a wide range of nervous system injuries, however there are negative clinical studies that have...
Progesterone has been shown to have neuroprotective capabilities against a wide range of nervous system injuries, however there are negative clinical studies that have failed to demonstrate positive effects of progesterone therapy. Specifically, we looked into whether progesterone receptors or its metabolizing enzymes, cytochrome P450c17 and 5α-reductase, are involved in the effects of progesterone on neuropathic pain after chronic constriction injury (CCI) of the sciatic nerve in mice. Intrathecal progesterone administration during the induction phase of chronic pain enhanced mechanical allodynia development and spinal glial fibrillary acidic protein (GFAP) expression, and this enhancement was inhibited by administration of ketoconazole, a P450c17 inhibitor, but not finasteride, a 5α-reductase inhibitor. Furthermore, phospho-serine levels of P450c17 in the spinal cord were elevated on day 1 after CCI operation, but not on day 17. In contrast, intrathecal progesterone administration during the maintenance phase of chronic pain decreased the acquired pain and elevated GFAP expression; this inhibition was restored by finasteride administration, but not by ketoconazole. The modification of mechanical allodynia brought on by progesterone in CCI mice was unaffected by the administration of mifepristone, a progesterone receptor antagonist. Collectively, these findings imply that progesterone suppresses spinal astrocyte activation via 5α-reductase activity during the maintenance phase of chronic pain and has an analgesic impact on the mechanical allodynia associated with the growing neuropathy. Progesterone, however, stimulates spinal astrocytes during the induction stage of peripheral neuropathy and boosts the allodynic impact caused by CCI through early spinal P450c17 activation.
PubMed: 38152690
DOI: 10.3389/fphar.2023.1253901 -
Cureus Nov 2023Background Medical termination of pregnancy (MTP) pills, primarily comprising mifepristone and misoprostol, have proven highly effective and safe under medical...
Background Medical termination of pregnancy (MTP) pills, primarily comprising mifepristone and misoprostol, have proven highly effective and safe under medical supervision. However, unsupervised MTP pill use is on the rise, posing serious health risks. Unsafe abortions remain a global public health concern, with a high incidence in developing countries like India. Methods We conducted a cross-sectional study at a tertiary healthcare center in India from February to April 2023. We enrolled 150 women with a history of unsupervised MTP pill use. Data were collected using structured questionnaires, including demographic information, awareness, sources of information, reasons for self-medication, and knowledge of complications. Results The majority of participants (50%) were aged 25-29 years. Low-income women (<3000pc) constituted 46.66% of the sample. Husbands played a significant role in advocating MTP pill use (57.33%). Ninety percent of pills were obtained directly from pharmacies. Shockingly, 97.3% of women were unaware of MTP pill complications, and 84% did not follow the recommended regimen. Significant associations were found between income, religion, education, age, parity, and reasons for self-medication, as well as recommendations for MTP pill use. Conclusion Our study revealed a diverse demographic of women seeking unsupervised MTP pill intake. Low-income women were disproportionately affected, emphasizing the need for improved healthcare access and education. Husbands played a crucial role in advocating MTP pill use, highlighting the importance of including men in reproductive health discussions. Lack of awareness and non-adherence to recommended regimens posed substantial risks. To combat unsafe abortions, a multifaceted approach is needed. Reproductive health education, regulatory measures, improved healthcare accessibility, and tailored interventions are essential.
PubMed: 38143596
DOI: 10.7759/cureus.49321 -
PloS One 2023Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with...
Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with the synthetic steroid mifepristone decreases egg production, reduces midgut size, and increases life span. Here, several gene mutations were assayed to investigate possible mechanisms for mifepristone action. Drosophila Dhr96 is a hormone receptor, and a key positive regulator of midgut lipid uptake and metabolism. Dhr96[1] null mutation increased female life span, and reduced the effects of mifepristone on life span, suggesting that Dhr96[1] mutation and mifepristone may act in part through the same mechanism. Consistent with this idea, lipidomics analysis revealed that mating increases whole-body levels of triglycerides and fatty-acids in triglycerides, and these changes are reversed by mifepristone. Maternal tudor[1] mutation results in females that lack the germ-line and produce no eggs. Maternal tudor[1] mutation increased mated female life span, and reduced but did not eliminate the effects of mating and mifepristone on life span. This indicates that decreased egg production may be related to the life span benefits of mifepristone, but is not essential. Mifepristone increases life span in w[1118] mutant mated females, but did not increase life span in w[1118] mutant virgin females. Mifepristone decreased egg production in w[1118] mutant virgin females, indicating that decreased egg production is not sufficient for mifepristone to increase life span. Mifepristone increases life span in virgin females of some, but not all, white[+] and mini-white[+] strains. Backcrossing of mini-white[+] transgenes into the w[1118] background was not sufficient to confer a life span response to mifepristone in virgin females. Taken together, the data support the hypothesis that mechanisms for mifepristone life span increase involve reduced lipid uptake and/or metabolism, and suggest that mifepristone may increase life span in mated females and virgin females through partly different mechanisms.
Topics: Animals; Female; Male; Drosophila; Drosophila melanogaster; Lipids; Longevity; Mifepristone; Mutation; Sexual Behavior, Animal; Triglycerides
PubMed: 38127988
DOI: 10.1371/journal.pone.0292820 -
Anatomy & Cell Biology Mar 2024Glucocorticoids play a physiologic role in the adult male reproductive functions, modulating gonadal steroid synthesis and spermatogenesis, through the glucocorticoid...
Glucocorticoids play a physiologic role in the adult male reproductive functions, modulating gonadal steroid synthesis and spermatogenesis, through the glucocorticoid receptor (GR). The expression of GR has been described in several key testicular cell types, including somatic cells and early germ cell populations. Nothing is known on GR in human spermatozoa. Herein, we explored the GR expression and its possible role in normal and testicular varicocele semen samples from volunteer donors. After semen parameter evaluation by macro- and microscopic analysis, samples were centrifuged; then spermatozoa and culture media were recovered for further investigations. By western blotting and immunofluorescence analyses we evidenced for the first time in spermatozoa the presence of GR-D3 isoform which was reduced in sperm from varicocele patients. By treating sperm with the synthetic glucocorticoid dexamethasone (DEXA), we found that survival, motility, capacitation, and acrosome reaction were increased in both healthy and varicocele samples. GR involvement in mediating DEXA effects, was confirmed by using the GR inhibitor mifepristone (M2F). Worthy, we also discovered that sperm secretes different cortisol amounts depending on its physio-pathological status, suggesting a defence mechanism to escape the immune system attach in the female genital tract thus maintaining the immune-privilege as in the testis. Collectively, our data suggests a role for glucocorticoids in determining semen quality and function, as well as in participating on sperm immune defensive mechanisms. The novelty of this study may be beneficial and needs to take into account in artificial insemination/drug discovery aimed to enhancing sperm quality.
PubMed: 38098241
DOI: 10.5115/acb.23.164 -
Biology of Reproduction Mar 2024Maternal decidual cells are crucial for the maintenance of canine pregnancy as they are the only cells expressing the nuclear progesterone (P4) receptor (PGR) in the...
Maternal decidual cells are crucial for the maintenance of canine pregnancy as they are the only cells expressing the nuclear progesterone (P4) receptor (PGR) in the placenta. Interfering with P4/PGR signaling adversely affects decidual cells and terminates pregnancy. Although immortalized dog uterine stromal (DUS) cells can be decidualized in vitro using cAMP, the involvement of cAMP-dependent kinases in canine decidualization had not been investigated. Therefore, the present project investigated changes in the kinome of DUS cells following in vitro decidualization, using the serine/threonine kinase (STK) PamChip assay (PamGene). Decidualization led to a predicted activation of 85 STKs in DUS cells, including protein kinase (PK) A, PKC, extracellular signal-regulated kinase (ERK)1/2 and other mitogen-activated protein kinases (MAPKs), calcium/calmodulin-dependent protein kinases (CAMKs), and Akt1/2. In addition, blocking PGR with type 2 antigestagens (aglepristone or mifepristone) decreased the activity of virtually all kinases modulated by decidualization. The underlying transcriptional effects were inferred from comparison with available transcriptomic data on antigestagen-mediated effects in DUS cells. In targeted studies, interfering with PKA or MAPK kinase (MEK)1/2 resulted in downregulation of important decidualization markers (e.g., insulin-like growth factor 1 (IGF1), prostaglandin E2 synthase (PTGES), prolactin receptor (PRLR), PGR, and prostaglandin-endoperoxide synthase 2 (PTGS2/COX2)). Conversely, blocking of PKC decreased the mRNA availability of IGF1, PGR, and PTGS2, but not of PTGES and PRLR. Moreover, suppressing PKA decreased the phosphorylation of the transcription factors cJUN and CREB, whereas blocking of PKC affected only cJUN. This first kinomics analysis to target decidualization showed an increased activity of a wide range of STKs, which could be hindered by disrupting P4/PGR signaling. Decidualization appears to be regulated in a kinase-dependent manner, with PKA and PKC evoking different effects.
Topics: Pregnancy; Female; Dogs; Animals; Decidua; Cyclooxygenase 2; Uterus; Progesterone; Placenta; Protein Serine-Threonine Kinases; Stromal Cells
PubMed: 38079525
DOI: 10.1093/biolre/ioad170 -
Journal of Family Medicine and Primary... Oct 2023Misoprostol is widely used in the medical management of missed abortions. However, pretreatment with Mifepristone has shown to be effective but still not recommended to...
INTRODUCTION
Misoprostol is widely used in the medical management of missed abortions. However, pretreatment with Mifepristone has shown to be effective but still not recommended to be used in missed abortions.
AIMS AND OBJECTIVES
To compare the outcome of medically managed missed abortion or blighted ovum using combination regime (Mifepristone and Misoprostol) vs Misoprostol alone.
MATERIALS AND METHODS
It was a prospective single-centre study performed in the Department of Obstetrics and Gynaecology, HIMSR and HAHC hospital, New Delhi, over, for one year. All the patients with diagnosed missed abortions were randomized into two groups (Group A and Group B). Group A was given Mifepristone 200 mg orally followed by Misoprostol 800 microgram per vaginal. Group B was given Misoprostol 800 microgram per vaginal. All the patients were observed for 24 hours for the expulsion of products of conception following the given regime. Ethical approval was taken from the Institutional Ethical Committee.
RESULTS
Both groups were comparable in demographic characteristics. On applying Fisher's exact test, it has been observed that the odds of nonexpulsion of the product of conception, time taken in expulsion, and surgical evacuation because of excessive bleeding were significantly higher in Group B (Misoprostol) compared with Group A (Mifepristone followed by Misoprostol). The cost-effective analysis showed that the cost is higher among Misoprostol Group B compared with combination drugs of Group A (Mifepristone + Misoprostol), but this result is not significant.
CONCLUSION
Mifepristone can be considered before Misoprostol in missed abortions. This regime might decrease the need for surgical evacuation.
PubMed: 38074237
DOI: 10.4103/jfmpc.jfmpc_503_23 -
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 -
Contraception Mar 2024This study aimed to perform a "proof of concept" pilot and assess patient satisfaction of pharmacist provision of medication abortion utilizing an implementation toolkit.
OBJECTIVES
This study aimed to perform a "proof of concept" pilot and assess patient satisfaction of pharmacist provision of medication abortion utilizing an implementation toolkit.
STUDY DESIGN
Pharmacists completed an online and in-person training followed by an online assessment prior to participating in the pilot. Pharmacists provided medication abortion care using a "no-test" protocol and an implementation toolkit. Participants were administered 200 mg of mifepristone orally on the day of their abortion visit and instructed to take 800 mcg of misoprostol buccally 24 to 48 hours later (with an additional 800 mcg buccally 4 hours after the first dose for patients 63-70 days' gestation). Visits were completed in person in a private room adjacent to the pharmacy. We assessed the rate of completed abortions and any complications. Following their abortion, patients completed a brief interviewer-administered survey and semistructured qualitative interview.
RESULTS
Ten patients completed medication abortion visits. Nine of 10 participants had complete abortions. One participant identified that she did not pass her pregnancy and underwent an in-office aspiration. One participant visited an emergency department for pain and received pain medication. No serious adverse events occurred. All patients completed the postabortion survey, and all were "very satisfied" with their abortion experience. Nine patients completed postabortion interviews.
CONCLUSIONS
In this pilot study, pharmacists were successful at providing medication abortion to patients. Satisfaction was high, and complications were uncommon.
IMPLICATIONS
Patients were highly satisfied with pharmacist provision of medication abortion and are likely to utilize this service if available.
Topics: Humans; Pregnancy; Female; Pharmacists; Pilot Projects; Abortion, Induced; Mifepristone; Misoprostol; Abortion, Spontaneous; Pain; Abortifacient Agents, Nonsteroidal
PubMed: 38065286
DOI: 10.1016/j.contraception.2023.110346 -
Cureus Nov 2023Mifepristone and misoprostol are globally used medications that have become disparaged through the stigmatization of reproductive healthcare. Patients are hindered from... (Review)
Review
Mifepristone and misoprostol are globally used medications that have become disparaged through the stigmatization of reproductive healthcare. Patients are hindered from receiving prompt treatment in clinical scenarios where misoprostol and mifepristone are the drugs of choice. It is no exaggeration to emphasize that in cases where reproductive healthcare is concerned. The aim of this paper is to discuss the different indications of mifepristone and to delineate where the discrepancy in accessibility arises. For this systematic review, we included publications citing clinical trials involving the use and efficacy of mifepristone published in English within the date range of 2000 to 2023. Five databases were searched to identify relevant sources. These databases are Google Scholar, MEDLINE with full text through EBSCO, and three National Center for Biotechnology Information (NCBI) databases (NCBI Bookshelf, PubMed, and PubMed Central). Twenty-three records were ultimately included in this review. Mifepristone has been shown to have therapeutic effects in the treatment of psychiatric disorders, such as major depressive disorder and psychotic depression. There was a significant decrease in depression and psychiatric rating symptoms for patients taking mifepristone versus placebo with no adverse events. Mifepristone has also been shown to improve treatment course in patients with Cushing's disease (CD) who failed or are unable to undergo surgical treatment. In addition, mifepristone has been shown to be a successful treatment option for adenomyosis and leiomyomas. Patients had a statistically significant decrease in uterine volumes following mifepristone treatment, which aided in the alleviation of other symptoms, such as blood loss and pelvic discomfort. Mifepristone is a synthetic steroid that has immense potential to provide symptomatic relief in patients suffering from a wide array of complicated diseases. Historically, mifepristone has been proven to have an incredible safety profile. While further research is certainly needed, the politicization of its medical use for only one of its many indications has unfortunately led to the willful ignorance of its potential despite its evidence-based safety profile and efficacy.
PubMed: 38060710
DOI: 10.7759/cureus.48372 -
Contraception Mar 2024This study aimed to understand individual experiences with medication abortion using misoprostol-only among people living in the United States.
OBJECTIVES
This study aimed to understand individual experiences with medication abortion using misoprostol-only among people living in the United States.
STUDY DESIGN
We conducted 31 semistructured anonymous in-depth interviews with individuals who used misoprostol-only for self-managed medication abortion. Participants were recruited from Aid Access, an online telemedicine organization that provided prescriptions for misoprostol to eligible people in all 50 states in May and June 2020 when a combined mifepristone and misoprostol regimen was unavailable. We coded transcripts with a flexible coding approach and focused on perceptions and experiences with use.
RESULTS
Participants were knowledgeable about misoprostol. Previous abortion experiences shaped perceptions of misoprostol-only by allowing comparison to the mifepristone and misoprostol regimen. Most participants expressed an unwavering desire for an effective abortion method, regardless of the medications or regimen. Individual physical experiences with misoprostol, including bleeding, cramping, nausea, and diarrhea, varied in intensity and duration. Participants proactively managed symptoms with self-care strategies and drew extensively from their prior experiences with menstruation, miscarriage, abortion, and childbirth. Clear instructions and information on potential complications and what to expect throughout the abortion fostered a sense of preparedness, and personalized interactions with an online help desk brought comfort.
CONCLUSIONS
Misoprostol offered an essential abortion method for study participants. This regimen was physically challenging for some, and there is potentially a greater need for communication and support for individuals using misoprostol-only regimens. Prior reproductive experiences informed participant's knowledge, preparedness, pain management, and ability to both recognize and manage potential complications.
IMPLICATIONS
As restrictions on mifepristone continue, more people may use misoprostol-only regimens. All regimens can be supported with detailed instructions, clear expectations, information on signs of potential complications, and personalized support. To achieve reproductive autonomy, people must have access to a range of abortion care options that meet their needs.
Topics: Pregnancy; Female; Humans; United States; Misoprostol; Mifepristone; Abortion, Spontaneous; Self-Management; Abortion, Induced; Pharmacy
PubMed: 38049047
DOI: 10.1016/j.contraception.2023.110345