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Contraception Dec 2022Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of... (Review)
Review
INTRODUCTION
Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of mifepristone and misoprostol. Medical abortion is known to be a painful process, but the optimal method of pain management is unclear. We sought to identify and compare pain management regimens for medical abortion before 14 weeks' gestation.
STUDY DESIGN
We conducted our search in August 2019 and included randomized controlled trials (RCT) and observational studies of any pain relief intervention (pharmacological and non-pharmacological) for mifepristone-misoprostol combination medical abortion of pregnancies less than 14 weeks' gestation.
RESULTS
We included four RCTs and one observational study. Due to the heterogeneity of study designs, interventions and outcome reporting, meta-analysis was not possible. Only one study found evidence of an effect between interventions on pain score: a prophylactic dose of ibuprofen 1600mg likely reduces the pain score when compared to a dose of paracetamol 2000mg (MD 2.26/10 [CI 3-1.52 lower]). For other interventions (pregabalin 300mg vs placebo; ibuprofen 800mg vs placebo; therapeutic vs prophylactic administration of ibuprofen 800mg; ambulation vs non-ambulation during treatment) there appeared to be little to no difference with comparator.
CONCLUSIONS
The findings of this review provide some support for the use of ibuprofen as a single dose given with misoprostol prophylactically, or in response to pain as needed. The optimal dosing of ibuprofen is unclear, but a single dose of ibuprofen 1600mg was shown to be effective and it was less certain whether 800mg was effective.
Topics: Humans; Female; Pregnancy; Pain Management; Misoprostol; Mifepristone; Ibuprofen; Pain; Observational Studies as Topic
PubMed: 36055363
DOI: 10.1016/j.contraception.2022.08.005 -
Advances in Therapy Jun 2019Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among the reasons for this is the degree of cervical dilation required to... (Review)
Review
Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among the reasons for this is the degree of cervical dilation required to safely extricate fetal parts. Cervical dilation is traditionally achieved by placing multiple sets of osmotic dilators over two or more days prior to the evacuation procedure; however, there is interest in shortening cervical preparation time. The use of adjuvant mifepristone and misoprostol in conjunction with osmotic dilators has been studied for this purpose, and their use demonstrates that adequate cervical dilation can be achieved in less time than with dilators alone. We present a review of the current evidence surrounding adjunctive agents for cervical preparation, and contend that for women presenting for surgical abortion care above 19 weeks gestation, the use of adjunctive mifepristone and/or misoprostol should be strongly considered along with osmotic dilator insertion when cervical preparation in less than 24 h is needed.
Topics: Abortifacient Agents, Nonsteroidal; Adult; Cervix Uteri; Dilatation; Extraction, Obstetrical; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Preoperative Care
PubMed: 31004327
DOI: 10.1007/s12325-019-00953-2 -
The Journal of Toxicological Sciences 2022We examined that an estradiol-dominant state against progesterone could affect hematological parameters through hemodilution because estradiol is known to increase...
We examined that an estradiol-dominant state against progesterone could affect hematological parameters through hemodilution because estradiol is known to increase plasma volume via oncotic pressure. We performed a 2- and 3-week repeated oral dose study with mifepristone, a progesterone receptor antagonist, in female rats and examined erythrocyte counts, hemoglobin, hematocrit, plasma volume, levels of estradiol and progesterone, water intake, and water loss. Mifepristone treatment decreased some hematological parameters mildly and increased plasma volume. There were no remarkable changes in the balance of water intake and water loss through urination. Both estradiol and progesterone levels and the ratio of estradiol to progesterone increased. Therefore, our findings indicate that repeated mifepristone treatment increases estradiol levels and plasma volume, resulting in lower erythrocyte counts, hemoglobin, and hematocrit. The present study proved the possible contribution of estradiol to understanding the toxicological significance of mifepristone-induced hemodilution.
Topics: Animals; Estradiol; Female; Hemodilution; Hemoglobins; Mifepristone; Progesterone; Rats; Water
PubMed: 35786681
DOI: 10.2131/jts.47.301 -
Contraception Apr 2018We aimed to document the experience of buying abortion pills from online vendors that do not require a prescription and to evaluate the active ingredient content of the...
OBJECTIVES
We aimed to document the experience of buying abortion pills from online vendors that do not require a prescription and to evaluate the active ingredient content of the pills received.
STUDY DESIGN
We searched the internet to identify a convenience sample of websites that sold mifepristone and misoprostol to purchasers in the United States and attempted to order these products. We documented price, shipping time and other aspects of ordering. We sent the samples received to a testing laboratory that measured the amount of active ingredient in individual tablets.
RESULTS
We identified 18 websites and ordered 22 products: 20 mifepristone-misoprostol combination products and 2 that contained only misoprostol. We received 18 combination products and the 2 misoprostol products from 16 different sites. No site required a prescription or any relevant medical information. The time between order and receipt of the 20 products ranged from 3 to 21 business days (median 9.5 days). The price for the 18 combination products ranged from $110 to $360, including shipping and fees; the products without mifepristone cost less. Chemical assays found that the 18 tablets labeled 200 mg mifepristone contained between 184.3 mg and 204.1 mg mifepristone, while the 20 tablets labeled 200 mcg misoprostol contained between 34.1 mcg and 201.4 mcg of the active ingredient.
CONCLUSIONS
Obtaining abortion medications from online pharmaceutical websites is feasible in the United States. The mifepristone tablets received contained within 8% of the labeled amount of active agent. The misoprostol tablets all contained that compound but usually less than labeled.
IMPLICATIONS STATEMENT
Given our findings, we expect that some people for whom clinic-based abortion is not easily available or acceptable may consider self-sourcing pills from the internet to be a rational option.
Topics: Abortion, Induced; Counterfeit Drugs; Drug Costs; Drug Therapy, Combination; Female; Health Services Accessibility; Humans; Internet; Mifepristone; Misoprostol; Pregnancy; United States
PubMed: 29030227
DOI: 10.1016/j.contraception.2017.09.016 -
The Cochrane Database of Systematic... Jul 2017Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.
OBJECTIVES
To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.
SEARCH METHODS
We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.
MAIN RESULTS
We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis.
AUTHORS' CONCLUSIONS
Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
Topics: Danazol; Dysmenorrhea; Dyspareunia; Endometriosis; Estrenes; Female; Gestrinone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Mifepristone; Norpregnadienes; Oximes; Prevalence; Randomized Controlled Trials as Topic; Receptors, Progesterone
PubMed: 28742263
DOI: 10.1002/14651858.CD009881.pub2 -
Medicine Aug 2023Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.
METHODS
We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.
RESULT
Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.
CONCLUSION
For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Topics: Female; Humans; Endometriosis; Danazol; Gestrinone; Leuprolide; Mifepristone; Network Meta-Analysis; Levonorgestrel
PubMed: 37543781
DOI: 10.1097/MD.0000000000034496 -
Contraception May 2020To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and...
OBJECTIVES
To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and middle-income countries.
STUDY DESIGN
From November 2017 to February 2018 mifepristone, misoprostol, and combined mifepristone-misoprostol (combipack) products were collected to populate the Medical Abortion Commodities Database. We extracted stated indications for use, storage instructions, and date of last revision from each package insert obtained. For those inserts listing medical abortion as an indication, we also extracted eligibility criteria, recommended regimens, side effects, and contraindications.
RESULTS
We identified 41 package inserts from 20 countries; 19 (46%) listed medical abortion as an indication including all 7 combipacks, all 7 mifepristone products, and 5/27 (19%) misoprostol products. Date of last insert revision ranged from 1991 to 2016. Gestational age limits for early medical abortion ranged from 49 days to "first trimester." Three (43%) mifepristone products recommended a 600 mg oral dose and two (29%) recommended regimens with gemeprost. Eighteen (67%) misoprostol and one (14%) combipack inserts recommended protection from moisture.
CONCLUSIONS
The characteristics, clinical information, and storage instructions in medical abortion product package inserts from a variety of field settings in low- and middle-income countries included inadequate storage instructions and outdated gestational age limits and regimens.
IMPLICATIONS
There is an urgent need to revisit approved inserts for medical abortion products in low- and middle-income countries to ensure information is accurate and reflects the current evidence base. Simultaneously, providing supplemental instructions targeted at users may fill some gaps. People have a right to accurate information to ensure a safe and effective medical abortion experience.
Topics: Abortifacient Agents; Abortion, Induced; Alprostadil; Cross-Sectional Studies; Developing Countries; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Product Labeling; Treatment Outcome
PubMed: 32032639
DOI: 10.1016/j.contraception.2020.01.011 -
BMC Pharmacology & Toxicology Jul 2022As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported...
BACKGROUND
As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported that mifepristone may cause cell death in decidual cells and result in hemorrhage of the decidua and insufficient blood supply. However, little is known about the histological effects of mifepristone on human decidua and chorion.
METHODS
Histological and subcellular structural changes of decidua and chorionic villi from women taking mifepristone at early pregnancy times were examined by Hematoxylin and eosin (H&E) staining and transmission Electron microscope. The expression of apoptosis-related proteins Bax/Bcl-2 was examined by immunohistochemistry.
RESULTS
After 48 h of mifepristone administration, the decidua tissue and chorionic villus structures were altered in women within 39-49 days of gestation and displayed varying degrees of degeneration and necrosis-like features. Apoptotic events were observed in the decidua and chorionic villi of early pregnancy, and mifepristone treatment significantly increases the number of apoptotic cells. The increased apoptotic events were concomitant with the increased expression of Bax and decreased expression of Bcl-2.
CONCLUSION
This study provides evidence that mifepristone induces histological and subcellular changes in decidua and chorionic villi. Mifepristone modulates the relative ratio of Bax/Bcl-2 and the increased apoptosis contributes to the pregnancy termination at early stage of pregnancy.
Topics: Chorionic Villi; Decidua; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Proto-Oncogene Proteins c-bcl-2; bcl-2-Associated X Protein
PubMed: 35869506
DOI: 10.1186/s40360-022-00592-4 -
The New England Journal of Medicine Jun 2016
Topics: Abortifacient Agents, Steroidal; Drug Labeling; Female; Government Regulation; Humans; Mifepristone; Pregnancy; State Government; United States; United States Food and Drug Administration
PubMed: 27276566
DOI: 10.1056/NEJMe1604462 -
Experimental and Clinical... Jun 2019Mifepristone, a type II glucocorticoid receptor antagonist, is under investigation as a potential pharmacotherapy for alcohol use disorder. This study examined effects...
Mifepristone, a type II glucocorticoid receptor antagonist, is under investigation as a potential pharmacotherapy for alcohol use disorder. This study examined effects of chronic administration of mifepristone on alcohol-seeking and self-administration in large nonhuman primates. Adult baboons ( = 5) self-administered alcohol 7 days/week under a chained schedule of reinforcement (CSR). The CSR comprised 3 components in which distinct cues were paired with different schedule requirements, with alcohol available for self-administration only in the final component, to model different phases of alcohol anticipation, seeking, and consumption. Under baseline conditions, baboons self-administered an average of 1g/kg/day of alcohol in the self-administration period. Mifepristone (10, 20, and 30 mg/kg) or vehicle was administered orally 30 min before each CSR session for 7 consecutive days. In a separate group of baboons ( = 5) acute doses of mifepristone (10, 20, and 30 mg/kg) were administered, and blood samples were collected over 72 hr to examine mifepristone pharmacokinetics. Some samples also were collected from the baboons that self-administered alcohol under the CSR after the chronic mifepristone condition. Mifepristone did not alter alcohol-seeking or self-administration under the CSR when compared with the vehicle condition. Mifepristone pharmacokinetics were nonlinear, and appear to be capacity limited. In sum, mifepristone did not reduce alcohol-maintained behaviors when administered to baboons drinking 1g/kg daily. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Topics: Alcohol Drinking; Alcoholism; Animals; Cues; Ethanol; Male; Mifepristone; Papio; Reinforcement Schedule; Self Administration
PubMed: 30570274
DOI: 10.1037/pha0000246