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Medicine Sep 2017There are some fertility-sparing treatments in patients with early endometrial cancer (EEC) or atypical complex hyperplasia (ACH), and the objective is to compare them... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are some fertility-sparing treatments in patients with early endometrial cancer (EEC) or atypical complex hyperplasia (ACH), and the objective is to compare them by evaluating the oncologic and reproductive outcomes.
METHODS
We searched the published literature using Medline, Cochrane, EMBASE, and Google Scholar databases up to January 3, 2017, with various combinations of keywords fertility-sparing treatments, progesterone, progestin, intrauterine devices, early endometrial cancer, and atypical complex hyperplasia. The primary endpoint is the complete response (CR) rate, and the secondary endpoints are the partial response (PR) rate, relapse rate (RR), pregnancy rate, and live birth rate.
RESULTS
Twenty-eight studies containing 1038 women with EEC or ACH were included for review and meta-analysis. The results demonstrated that women with EEC or ACH managed with progestin had a pooled CR rate of 71% (95% confidence interval [CI]: 63-77%). The pooled pregnancy outcomes showed that 34% of women taking progestin treatment for EEC or ACH became pregnant (95% CI: 30-38%); however, only 20% of them delivered live newborns. The pooled CR rate for women using intrauterine device (IUD) was 76% (95% CI: 67-83%), and pooled RR was 9% (95% CI: 5-17%). The pregnancy rate for women whom underwent IUD was 18% (95% CI: 7-37%), and 14% of them delivered live newborns. In patients using progestin plus IUD, the pooled CR rate was 87% (95% CI: 75-93%); among those patients, 40% became pregnant (95% CI: 20-63%), and 35% delivered live newborns. There is no publication bias for the CR rate.
CONCLUSION
For patients with EEC and ACH, treatments with progestin, with or without IUD, or IUD alone can reach good CR rate; however, the pregnancy outcomes might be worse in patients treated with IUD alone. Further randomized-controlled studies are warranted to find out a better solution.
Topics: Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hyperplasia; Organ Sparing Treatments; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 28906392
DOI: 10.1097/MD.0000000000008034 -
Frontiers in Cardiovascular Medicine 2023The use of oral contraceptives (OCs) is associated with an increased risk of cardiovascular events such as arterial and venous thrombosis (VTE). Cardiovascular diseases... (Review)
Review
BACKGROUND
The use of oral contraceptives (OCs) is associated with an increased risk of cardiovascular events such as arterial and venous thrombosis (VTE). Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with low- and middle-income nations accounting for over three-quarter of CVD deaths. The aim of this systematic review is to provide a comprehensive synthesis of the available evidence on the link between OC use and CVD risk in premenopausal women and to further assess the role of geographic disparities in the reported prevalence of CVD risk in women on OCs.
METHODS
A comprehensive search of databases such as MEDLINE, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Health Source: Nursing/Academic Edition was conducted, right from the inception to the present, by using the EBSCOhost search engine. The Cochrane Central Register of Clinical trials (CENTRAL) was also searched to augment relevant sources of information. OpenGrey, which is a repository of information providing open access to bibliographical references, was searched and the reference list of the selected studies was also scanned. The potential risk of bias of the included studies was assessed using the modified Downs and Black checklist. Data analysis was performed using the Review Manager (RevMan) version 5.3.
RESULTS
We included 25 studies that comprised 3,245 participants, of which 1,605 (49.5%) are OC users, while 1,640 (50.5%) are non-OC users. A total of 15 studies were included for meta-analysis, and the overall pooled estimates suggested a significant increase in the traditional cardiovascular risk variables [standardized mean difference (SMD) = 0.73, (0.46, 0.99) ( = 5.41, < 0.001)] and little to no difference in endothelial activation among OC users when compared with non-OC users [SMD = -0.11, (-0.81, 0.60) ( = 0.30, = 0.76)]. Europe [SMD = 0.03, (-0.21, 0.27), ( = 0.25 = 0.88)] had the least effect size, while North America had the highest effect size [SMD = 1.86, (-0.31, 4.04), ( = 1.68 = 0.09)] for CVD risk in OC users when compared with non-OC users.
CONCLUSION
The use of OCs suggests a significant increase in the prevalence of traditional cardiovascular risk variables with little to no difference in the risk of endothelial dysfunction when compared with non-OC users, and the magnitude of CVD risks varies across different geographical regions.
REGISTRATION AND PROTOCOL
This systematic review was registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD42020216169.
PubMed: 37180788
DOI: 10.3389/fcvm.2023.1127104 -
Women's Health (London, England) 2022Implanon discontinuation before the recommended time is problematic, as it puts women at risk of unwanted pregnancies and unsafe abortions, along with negative maternal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Implanon discontinuation before the recommended time is problematic, as it puts women at risk of unwanted pregnancies and unsafe abortions, along with negative maternal health outcomes. Although the magnitude and determinants of Implanon discontinuation have been studied in Ethiopia, the results were inconsistent, with significant variability. Hence, this systematic review and meta-analysis aimed at estimating the pooled prevalence of Implanon discontinuation and its determinants in Ethiopia.
METHODS
A comprehensive search of studies published before 18 February 2022 was done using electronic databases such as PubMed, Embase, Google Scholar, Scopus, Web of Science, Science Direct, and Cochrane Library. The relevant data were extracted using a Microsoft Excel 2013 and analyzed using STATA Version 16. A random-effect meta-analysis model was used to compute pooled prevalence and odds ratio. The Cochrane test statistics and tests were used to assess the heterogeneity of the included studies. A funnel plot, Begg's, and Egger's tests were used to check for the presence of publication bias.
RESULTS
A total of 11 studies with 4320 study participants were included in this meta-analysis. The overall pooled prevalence of Implanon discontinuation in Ethiopia was found to be 32.62% (95% confidence interval = 24.10, 41.13). There was significant heterogeneity among the included studies ( = 97.4%, < 0.001). However, there was no statistical evidence of publication bias ( = 0.533). Dissatisfied with service provision at the time of insertion (odds ratio = 3.92, 95% confidence interval = 1.54, 6.29), not having pre-insertion counseling (odds ratio = 2.98, 95% confidence interval = 1.91, 5.04), the absence of post-insertion follow-up (odds ratio = 4.03, 95% confidence interval = 2.17, 5.90), and the presence of side effects (odds ratio = 2.93, 95% confidence interval = 1.87, 3.98) were found to be determinants of Implanon discontinuation.
CONCLUSION
According to this systematic review and meta-analysis, one-third of Ethiopian women discontinued Implanon before the recommended time (3 years). Program managers and service providers should consider using more evidence-based and participatory counseling approaches to enhance client satisfaction. Furthermore, family planning service delivery points should be equipped to manage and reassure women who are experiencing side effects.
Topics: Black People; Desogestrel; Ethiopia; Female; Humans; Pregnancy; Prevalence
PubMed: 35762596
DOI: 10.1177/17455057221109222 -
BMC Medicine Oct 2022Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
METHODS
We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
RESULTS
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
CONCLUSIONS
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Topics: Elafin; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins; Immunologic Factors; Interferons; Interleukin 1 Receptor Antagonist Protein; Interleukin-16; Interleukin-1alpha; Interleukin-6; Interleukins; Lactoferrin; Menstrual Cycle; Muramidase; Progesterone; beta-Defensins
PubMed: 36195867
DOI: 10.1186/s12916-022-02532-9 -
Contraception Dec 2016Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated... (Review)
Review
BACKGROUND
Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated with an increased risk of ischemic stroke. Use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age.
OBJECTIVE
To identify evidence regarding the risk of arterial thromboembolism (stroke or myocardial infarction) among women with migraine who use hormonal contraceptives.
METHODS
We searched the PubMed database for all articles published from database inception through January 2016. We included studies that examined women with migraine overall or separated by subtype (with or without aura). Hormonal contraceptives of interest included combined hormonal methods (COCs, patch and ring) and progestin-only methods (progestin-only pills, injectables, implants and progestin intrauterine devices).
RESULTS
Seven articles met inclusion criteria. All were case-control studies of fair to poor quality reporting on use of COCs or oral contraceptives (OCs) not further described and all reported stroke outcomes. Four studies demonstrated that, among women with migraine (not separated by subtype), COC use was associated with approximately two to four times the risk of stroke compared with nonuse. The only study to examine specific migraine subtypes found an elevated risk of stroke among women with migraine with aura, and this risk was similar regardless of OC use, although these odds ratios were not reported. Two studies did not report risks among women with migraine and COC use combined, but both found increased risks of stroke with migraine and COC use independently. No evidence was found on other hormonal contraceptives or on risk of myocardial infarction.
CONCLUSION
Limited evidence suggests a two- to fourfold increased risk of stroke among women with migraine who use COCs compared with nonuse. Additional study is needed on the risks of hormonal contraceptives, including combined and progestin-only methods, among women with different migraine subtypes.
Topics: Contraceptive Devices, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans; Migraine Disorders; Myocardial Infarction; Progestins; Risk Assessment; Stroke
PubMed: 27153744
DOI: 10.1016/j.contraception.2016.04.016 -
Fertility and Sterility Apr 2017To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI).
DESIGN
An updated systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Patients undergoing OI-IUI for infertility.
INTERVENTION(S)
Exogenous P luteal support after OI-IUI.
MAIN OUTCOME MEASURE(S)
Live birth.
RESULT(S)
Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76).
CONCLUSION(S)
Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins.
Topics: Female; Fertility; Fertility Agents; Gonadotropins; Humans; Infertility; Insemination, Artificial; Live Birth; Luteal Phase; Odds Ratio; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Risk Factors; Treatment Outcome
PubMed: 28238492
DOI: 10.1016/j.fertnstert.2017.01.011 -
The Cochrane Database of Systematic... Jan 2017Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33%... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33% in its mild form and 3% to 8% in its moderate or severe form. These numbers might even be higher for high-risk women such as those with polycystic ovaries or a high oocyte yield from ovum pickup.
OBJECTIVES
The objective of this overview is to identify and summarise all evidence from Cochrane systematic reviews on interventions for prevention or treatment of moderate, severe and overall OHSS in couples with subfertility who are undergoing ART cycles.
METHODS
Published Cochrane systematic reviews reporting on moderate, severe or overall OHSS as an outcome in ART cycles were eligible for inclusion in this overview. We also identified Cochrane submitted protocols and title registrations for future inclusion in the overview. The evidence is current to 12 December 2016. We identified reviews, protocols and titles by searching the Cochrane Gynaecology and Fertility Group Database of Systematic Reviews and Archie (the Cochrane information management system) in July 2016 on the effectiveness of interventions for outcomes of moderate, severe and overall OHSS. We undertook in duplicate selection of systematic reviews, data extraction and quality assessment. We used the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the quality of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables.
MAIN RESULTS
We included a total of 27 reviews in this overview. The reviews were generally of high quality according to AMSTAR ratings, and included studies provided evidence that ranged from very low to high in quality. Ten reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Metformin treatment before and during an ART cycle for women with PCOS (moderate-quality evidence).• Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence).• GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence).• Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence).• Intravenous fluids (plasma expanders) around the time of hCG administration or oocyte pickup in ART cycles (very low-quality evidence).• Progesterone for luteal phase support in ART cycles (low-quality evidence).• Coasting (withholding gonadotrophins) - a promising intervention that needs to be researched further for reduction of OHSS.On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of embryo cryopreservation.
AUTHORS' CONCLUSIONS
Currently, 27 reviews in the Cochrane Library were conducted to report on or to try to report on OHSS in ART cycles. We identified four review protocols but no new registered titles that can potentially be included in this overview in the future. This overview provides the most up-to-date evidence on prevention of OHSS in ART cycles from all currently published Cochrane reviews on ART. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise other outcomes such as pregnancy or live birth rate. Review results, however, are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.
Topics: Cabergoline; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Metformin; Ovarian Hyperstimulation Syndrome; Pregnancy; Progesterone; Reproductive Techniques, Assisted; Review Literature as Topic
PubMed: 28111738
DOI: 10.1002/14651858.CD012103.pub2 -
The Cochrane Database of Systematic... Dec 2016Traumatic brain injury (TBI) is a leading cause of death and disability, and the identification of effective, inexpensive and widely practicable treatments for brain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic brain injury (TBI) is a leading cause of death and disability, and the identification of effective, inexpensive and widely practicable treatments for brain injury is of great public health importance worldwide. Progesterone is a naturally produced hormone that has well-defined pharmacokinetics, is widely available, inexpensive, and has steroidal, neuroactive and neurosteroidal actions in the central nervous system. It is, therefore, a potential candidate for treating TBI patients. However, uncertainty exists regarding the efficacy of this treatment. This is an update of our previous review of the same title, published in 2012.
OBJECTIVES
To assess the effects of progesterone on neurologic outcome, mortality and disability in patients with acute TBI. To assess the safety of progesterone in patients with acute TBI.
SEARCH METHODS
We updated our searches of the following databases: the Cochrane Injuries Group's Specialised Register (30 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2016), MEDLINE (Ovid; 1950 to 30 September 2016), Embase (Ovid; 1980 to 30 September 2016), Web of Science Core Collection: Conference Proceedings Citation Index-Science (CPCI-S; 1990 to 30 September 2016); and trials registries: Clinicaltrials.gov (30 September 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform (30 September 2016).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of progesterone versus no progesterone (or placebo) for the treatment of people with acute TBI.
DATA COLLECTION AND ANALYSIS
Two review authors screened search results independently to identify potentially relevant studies for inclusion. Independently, two review authors selected trials that met the inclusion criteria from the results of the screened searches, with no disagreement.
MAIN RESULTS
We included five RCTs in the review, with a total of 2392 participants. We assessed one trial to be at low risk of bias; two at unclear risk of bias (in one multicentred trial the possibility of centre effects was unclear, whilst the other trial was stopped early), and two at high risk of bias, due to issues with blinding and selective reporting of outcome data.All included studies reported the effects of progesterone on mortality and disability. Low quality evidence revealed no evidence of a difference in overall mortality between the progesterone group and placebo group (RR 0.91, 95% CI 0.65 to 1.28, I² = 62%; 5 studies, 2392 participants, 2376 pooled for analysis). Using the GRADE criteria, we assessed the quality of the evidence as low, due to the substantial inconsistency across studies.There was also no evidence of a difference in disability (unfavourable outcomes as assessed by the Glasgow Outcome Score) between the progesterone group and placebo group (RR 0.98, 95% CI 0.89 to 1.06, I² = 37%; 4 studies; 2336 participants, 2260 pooled for analysis). We assessed the quality of this evidence to be moderate, due to inconsistency across studies.Data were not available for meta-analysis for the outcomes of mean intracranial pressure, blood pressure, body temperature or adverse events. However, data from three studies showed no difference in mean intracranial pressure between the groups. Data from another study showed no evidence of a difference in blood pressure or body temperature between the progesterone and placebo groups, although there was evidence that intravenous progesterone infusion increased the frequency of phlebitis (882 participants). There was no evidence of a difference in the rate of other adverse events between progesterone treatment and placebo in the other three studies that reported on adverse events.
AUTHORS' CONCLUSIONS
This updated review did not find evidence that progesterone could reduce mortality or disability in patients with TBI. However, concerns regarding inconsistency (heterogeneity among participants and the intervention used) across included studies reduce our confidence in these results.There is no evidence from the available data that progesterone therapy results in more adverse events than placebo, aside from evidence from a single study of an increase in phlebitis (in the case of intravascular progesterone).There were not enough data on the effects of progesterone therapy for our other outcomes of interest (intracranial pressure, blood pressure, body temperature) for us to be able to draw firm conclusions.Future trials would benefit from a more precise classification of TBI and attempts to optimise progesterone dosage and scheduling.
Topics: Brain Injuries; Disability Evaluation; Glasgow Coma Scale; Humans; Injury Severity Score; Intracranial Pressure; Neuroprotective Agents; Progesterone; Randomized Controlled Trials as Topic; Risk
PubMed: 28005271
DOI: 10.1002/14651858.CD008409.pub4 -
The Cochrane Database of Systematic... May 2022Contraceptive implants are one of the most effective contraceptive methods, providing a long duration of pregnancy protection and a high safety profile. Hence this... (Review)
Review
BACKGROUND
Contraceptive implants are one of the most effective contraceptive methods, providing a long duration of pregnancy protection and a high safety profile. Hence this method is suitable for optimizing the interpregnancy interval, especially for women undergoing abortion. Women who have had abortions are at high risk of rapid repeat pregnancies. Provision of effective contraception at the time of an abortion visit can be a key strategy to increase access and uptake of contraception. A review of the evidence was needed to evaluate progestin-releasing implants for immediate use at the time of abortion, including whether immediate placement impacts the effectiveness of medical abortion, which relies on antiprogestogens.
OBJECTIVES
To compare contraceptive implant initiation rates, contraceptive effectiveness, and adverse outcomes associated with immediate versus delayed insertion of contraceptive implants following abortion.
SEARCH METHODS
We searched for all relevant studies regardless of language or publication status up to September 2019, with an update search in March 2021. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Ovid EBM Reviews), MEDLINE ALL (Ovid), Embase.com, CINAHL (EBSCOhost) (Cumulative Index to Nursing and Allied Health Literature), Global Health (Ovid), LILACS (Latin American and Caribbean Health Science Information database), Scopus, ClinicalTrials.gov, and the WHO ICTRP. We examined the reference lists of pertinent articles to identify other studies.
SELECTION CRITERIA
We sought randomized controlled trials (RCTs) comparing immediate versus delayed insertion of contraceptive implant for contraception following abortion.
DATA COLLECTION AND ANALYSIS
We followed the standard procedures recommended by Cochrane. To identify potentially relevant studies, two review authors (JS, LS) independently screened the titles, abstracts, and full texts of the search results, assessed trials for risk of bias, and extracted data. We computed the risk ratio (RR) with 95% confidence intervals (CIs) for binary outcomes, and the mean difference (MD) with 95% CIs for continuous variables.
MAIN RESULTS
We found three RCTs including a total of 1162 women. Our GRADE assessment of the overall certainty of the evidence ranged from moderate to very low, downgraded for risk of bias, inconsistency, and imprecision. Utilization rate at six months may be slightly higher for immediate compared with delayed insertion (RR 1.10, 95% CI 1.05 to 1.15; 3 RCTs; 1103 women; I = 62%; low certainty evidence). Unintended pregnancy within six months after abortion was probably lower with immediate insertion compared with delayed insertion (RR 0.25, 95% CI 0.08 to 0.77; 3 RCTs; 1029 women; I = 0%; moderate certainty evidence). Immediate insertion of contraceptive implants probably improves the initiation rate compared to delayed insertion following medical abortion (RR 1.26 for medical abortion, 95% CI 1.21 to 1.32; 2 RCTs; 1014 women; I = 89%; moderate certainty evidence) and may also improve initiation following surgical abortion (RR 2.32 for surgical abortion, 95% CI 1.79 to 3.01; 1 RCT; 148 women; I = not applicable; low certainty evidence). We did not pool results for the implant initiation outcome over both abortion types because of very high statistical heterogeneity. For medical termination of pregnancy, we found there is probably little or no difference between immediate and delayed insertion in overall failure of medical abortion (RR 1.18, 95% CI 0.58 to 2.40; 2 RCTs; 1001 women; I = 68%;moderate certainty evidence). There may be no difference between immediate and delayed insertion on rates of abnormal bleeding at one month after abortion (RR 1.00, 95% CI 0.88 to 1.14; 1 RCT; 462 women; I = not applicable; low certainty evidence).
AUTHORS' CONCLUSIONS
Provision of progestin-releasing implants concurrently with abortifacient agents likely has little or no negative impact on overall failure rate of medical abortion. Immediate insertion probably improves the initiation rate of contraceptive implant, as well as unintended pregnancy rate within six months after abortion, compared to delayed insertion. There may be no difference between immediate and delayed insertion approaches in bleeding adverse effects at one month after abortion.
Topics: Abortifacient Agents; Abortion, Induced; Abortion, Spontaneous; Contraceptive Agents; Female; Humans; Pregnancy; Pregnancy Rate; Progestins
PubMed: 35583092
DOI: 10.1002/14651858.CD013565.pub2 -
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