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Obstetrics and Gynecology Oct 2019To explore the relationship between intrauterine device (IUD) use and risk of ovarian cancer through systematic review of the literature and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the relationship between intrauterine device (IUD) use and risk of ovarian cancer through systematic review of the literature and meta-analysis.
DATA SOURCES
We searched MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection from inception to June 2018. For the MEDLINE search, we included the MeSH terms "intrauterine devices" AND "ovarian neoplasms," however also searching "intrauter*," "ovar*" and "fallopian tube," as well as "cancer" and "carcinoma" as keywords to include all possible variations. Similar search terms were used in the other databases. We also searched ClinicalTrials.gov.
METHODS OF STUDY SELECTION
Case-control and cohort studies that collected individual level data on IUD use and ovarian cancer diagnosis were critically reviewed and data extracted. Review of abstracts from 399 articles through systematic database review and an additional 200 articles through Google Scholar identified a total of 15 studies with individual level data regarding IUD use and incident ovarian cancer. On critical review, 11 of these studies were used for meta-analysis. All case reports and reviews were excluded.
TABULATION, INTEGRATION, AND RESULTS
The data were harmonized and weighted and summary odds ratios (ORs) were calculated. Covariates were identified evaluated separately. A random-effects meta-analysis was performed to confirm minimal bias. Harmonization and weighting of the data revealed an OR association between ever use of an IUD and incident ovarian cancer to be 0.68 (95% CI 0.62-0.75). There were no significant differences found between covariates. Heterogeneity among all studies was found to be I=68%.
CONCLUSION
Intrauterine device use is associated with a reduced incidence of ovarian cancer based on a review of existing retrospective data. Unfortunately, prospective investigation into the role of IUDs in ovarian cancer prevention is limited.
Topics: Female; Humans; Incidence; Intrauterine Devices; Ovarian Neoplasms; Retrospective Studies
PubMed: 31503144
DOI: 10.1097/AOG.0000000000003463 -
The European Journal of Contraception &... Apr 2017To assess the efficacy and tolerability (side-effects profile), and compliance of the combined contraceptive vaginal ring (CCVR) compared with combined oral hormonal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and tolerability (side-effects profile), and compliance of the combined contraceptive vaginal ring (CCVR) compared with combined oral hormonal contraceptives (COC).
DATA SOURCES
The PubMed, Embase, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, ClinicalTrials.gov, Clinical Trials Registry Platform (ICTRP) and CINAHL databases were searched.
METHODS OF STUDY SELECTION
Electronic databases were searched for randomised clinical trials comparing the CCVR with COC with a duration of at least 3 months between 01 December and 15 December 2015. The primary outcome was efficacy. The secondary outcomes were compliance, absence of withdrawal bleeding, breakthrough bleeding, nausea and headache. Heterogeneity was assessed using I statistic and Cochran's Q statistic. Results were expressed as odds ratios (OR) with 95% confidence intervals (CIs) using random-effects models or fixed-effects models depending on the heterogeneity.
RESULTS
4368 records were identified, 2844 of which were removed after duplicates and 1524 records were screened. Of these, 1503 were excluded and 21 full text articles were assessed for eligibility. After removing another 7 articles, 14 records were finally included in the qualitative and quantitative analysis. The results show a trend to higher efficacy for the CCVR in preventing pregnancy (Peto OR: 0.52 [95% CI: 0.26-1.04]) and a significantly lower presence of nausea (Peto OR: 0.66 [95% CI: 0.46-0.93]). More cycles were compliant in the CCVR group (Peto OR: 1.22 [95% CI: 1.12-1.32]) and fewer women reported breakthrough bleeding (Peto OR: 0.68 [95% CI: 0.51-0.91]).
CONCLUSIONS
Our findings demonstrate that the CCVR is as effective and tolerable as the COC but with a better bleeding profile.
Topics: Contraceptive Agents, Female; Contraceptive Devices, Female; Desogestrel; Drug Implants; Ethinyl Estradiol; Female; Humans
PubMed: 28256919
DOI: 10.1080/13625187.2017.1287351 -
Critical Care (London, England) Mar 2024Several bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit. It remains unclear which assessments perform best in predicting weaning success. The primary aim of this systematic review and meta-analysis was to summarize and compare the accuracy of the following assessments to predict weaning success: maximal inspiratory (PImax) and expiratory pressures, diaphragm thickening fraction and excursion (DTF and DE), end-expiratory (Tdi) and end-inspiratory (Tdi) diaphragm thickness, airway occlusion pressure (P0.1), electrical activity of respiratory muscles, and volitional and non-volitional assessments of transdiaphragmatic and airway opening pressures.
METHODS
Medline (via Pubmed), EMBASE, Web of Science, Cochrane Library and CINAHL were comprehensively searched from inception to 04/05/2023. Studies including adult mechanically ventilated patients reporting data on predictive accuracy were included. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate the SROC curves of each assessment method. Meta-regression was used to compare SROC curves. Sensitivity analyses were conducted by excluding studies with high risk of bias, as assessed with QUADAS-2. Direct comparisons were performed using studies comparing each pair of assessments within the same sample of patients.
RESULTS
Ninety-four studies were identified of which 88 studies (n = 6296) reporting on either PImax, DTF, DE, Tdi, Tdi and P0.1 were included in the meta-analyses. The sensitivity to predict weaning success was 63% (95% CI 47-77%) for PImax, 75% (95% CI 67-82%) for DE, 77% (95% CI 61-87%) for DTF, 74% (95% CI 40-93%) for P0.1, 69% (95% CI 13-97%) for Tdi, 37% (95% CI 13-70%) for Tdi, at fixed 80% specificity. Accuracy of DE and DTF to predict weaning success was significantly higher when compared to PImax (p = 0.04 and p < 0.01, respectively). Sensitivity and direct comparisons analyses showed that the accuracy of DTF to predict weaning success was significantly higher when compared to DE (p < 0.01).
CONCLUSIONS
DTF and DE are superior to PImax and DTF seems to have the highest accuracy among all included respiratory muscle assessments for predicting weaning success. Further studies aiming at identifying the optimal threshold of DTF to predict weaning success are warranted.
TRIAL REGISTRATION
PROSPERO CRD42020209295, October 15, 2020.
Topics: Adult; Humans; Ventilator Weaning; Respiration, Artificial; Respiratory Muscles; Diaphragm; ROC Curve
PubMed: 38454487
DOI: 10.1186/s13054-024-04823-4 -
Reproductive Health Nov 2021The intrauterine contraceptive device, a type of long-acting reversible contraception, is one of the most effective and safe contraceptive methods. In Ethiopia,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The intrauterine contraceptive device, a type of long-acting reversible contraception, is one of the most effective and safe contraceptive methods. In Ethiopia, intrauterine contraceptive device is little known and practised to delay pregnancy. Therefore, this study aimed to assess post-partum intrauterine contraceptive device utilisation and its associated factors among women in Ethiopia.
METHOD
In the current meta-analysis, variables were searched from different electronic database systems, including PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature. Data were extracted using a standardised data collection measurement tool. The data were also analysed by using STATA 16 statistical software. I tests assessed heterogeneity between the studies. A random-effect model was used to forecast the pooled utilisation of postpartum intrauterine contraceptive device.
RESULTS
Twelve full-article studies were included. The pooled prevalence of post-partum intrauterine contraceptive device among women in Ethiopia was 21.63%. Occupation (OR = 4.44, 95% CI, 2.24-8.81), educational level of college and above (OR = 5.93, 95% CI, 2.55-13.8), antenatal care (OR = 2.09, 95% CI, 1.4-3.12), age (OR = 4.8, 95% CI, 2.3-10.04), good knowledge (OR = 4.16, 95% CI, 1.65-10.49), counseling (OR = 3.05, 95%CI, 1.41-6.63), husband support (OR = 11.48, 95% CI, 6.05-21.79) and awareness about IUCD (OR = 3.86, 95% CI, 1.46-10.2) were positively associated with utilization of postpartum intrauterine contraception device.
CONCLUSIONS
Utilisation of post-partum intrauterine contraceptive device was significantly low. Scaling up women's educational status and ANC use has paramount importance in increasing post-partum IUD use, which further improves maternal and child health in general. This finding may be useful in both reproductive health promotion at an individual level and policy-making regarding this issue.
Topics: Child; Contraception; Ethiopia; Female; Humans; Intrauterine Devices; Postpartum Period; Pregnancy; Prenatal Care
PubMed: 34774058
DOI: 10.1186/s12978-021-01273-x -
Journal of Medical Internet Research Feb 2024A chatbot is a computer program that is designed to simulate conversation with humans. Chatbots may offer rapid, responsive, and private contraceptive information;... (Review)
Review
BACKGROUND
A chatbot is a computer program that is designed to simulate conversation with humans. Chatbots may offer rapid, responsive, and private contraceptive information; counseling; and linkages to products and services, which could improve contraceptive knowledge, attitudes, and behaviors.
OBJECTIVE
This review aimed to systematically collate and interpret evidence to determine whether and how chatbots improve contraceptive knowledge, attitudes, and behaviors. Contraceptive knowledge, attitudes, and behaviors include access to contraceptive information, understanding of contraceptive information, access to contraceptive services, contraceptive uptake, contraceptive continuation, and contraceptive communication or negotiation skills. A secondary aim of the review is to identify and summarize best practice recommendations for chatbot development to improve contraceptive outcomes, including the cost-effectiveness of chatbots where evidence is available.
METHODS
We systematically searched peer-reviewed and gray literature (2010-2022) for papers that evaluated chatbots offering contraceptive information and services. Sources were included if they featured a chatbot and addressed an element of contraception, for example, uptake of hormonal contraceptives. Literature was assessed for methodological quality using appropriate quality assessment tools. Data were extracted from the included sources using a data extraction framework. A narrative synthesis approach was used to collate qualitative evidence as quantitative evidence was too sparse for a quantitative synthesis to be carried out.
RESULTS
We identified 15 sources, including 8 original research papers and 7 gray literature papers. These sources included 16 unique chatbots. This review found the following evidence on the impact and efficacy of chatbots: a large, robust randomized controlled trial suggests that chatbots have no effect on intention to use contraception; a small, uncontrolled cohort study suggests increased uptake of contraception among adolescent girls; and a development report, using poor-quality methods, suggests no impact on improved access to services. There is also poor-quality evidence to suggest increased contraceptive knowledge from interacting with chatbot content. User engagement was mixed, with some chatbots reaching wide audiences and others reaching very small audiences. User feedback suggests that chatbots may be experienced as acceptable, convenient, anonymous, and private, but also as incompetent, inconvenient, and unsympathetic. The best practice guidance on the development of chatbots to improve contraceptive knowledge, attitudes, and behaviors is consistent with that in the literature on chatbots in other health care fields.
CONCLUSIONS
We found limited and conflicting evidence on chatbots to improve contraceptive knowledge, attitudes, and behaviors. Further research that examines the impact of chatbot interventions in comparison with alternative technologies, acknowledges the varied and changing nature of chatbot interventions, and seeks to identify key features associated with improved contraceptive outcomes is needed. The limitations of this review include the limited evidence available on this topic, the lack of formal evaluation of chatbots in this field, and the lack of standardized definition of what a chatbot is.
Topics: Adolescent; Female; Humans; Contraceptive Agents; Cohort Studies; Contraceptive Devices; Contraception; Communication; Randomized Controlled Trials as Topic
PubMed: 38412028
DOI: 10.2196/46758 -
Annals of Anatomy = Anatomischer... Jun 2024The aim of this systematic review is to study the subdiaphragmatic anatomy of the phrenic nerve. (Review)
Review
OBJECTIVE
The aim of this systematic review is to study the subdiaphragmatic anatomy of the phrenic nerve.
MATERIALS AND METHODS
A computerised systematic search of the Web of Science database was conducted. The key terms used were phrenic nerve, subdiaphragmat*, esophag*, liver, stomach, pancre*, duoden*, intestin*, bowel, gangli*, biliar*, Oddi, gallbladder, peritone*, spleen, splenic, hepat*, Glisson, falciform, coronary ligament, kidney, suprarenal, and adrenal. The 'cited-by' articles were also reviewed to ensure that all appropriate studies were included.
RESULTS
A total of one thousand three hundred and thirty articles were found, of which eighteen met the inclusion and exclusion criteria. The Quality Appraisal for Cadaveric Studies scale revealed substantial to excellent methodological quality of human studies, while a modified version of the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias Tool denoted poor methodological quality of animal studies. According to human studies, phrenic supply has been demonstrated for the gastro-esophageal junction, stomach, celiac ganglia, liver and its coronary ligament, inferior vena cava, gallbladder and adrenal glands, with half of the human samples studied presenting phrenic nerve connections with any subdiaphragmatic structure.
CONCLUSIONS
This review provides the first systematic evidence of subdiaphragmatic phrenic nerve supply and connections. This is of interest to professionals who care for people suffering from neck and shoulder pain, as well as patients with peridiaphragmatic disorders or hiccups. However, there are controversies about the autonomic or sensory nature of this supply.
Topics: Phrenic Nerve; Humans; Diaphragm; Animals
PubMed: 38692333
DOI: 10.1016/j.aanat.2024.152269 -
Reproductive Health Sep 2017Intra-uterine contraception (IUC) involves the use of an intra-uterine device (IUD), a highly effective, long-acting, reversible contraceptive method. Historically, the... (Review)
Review
BACKGROUND
Intra-uterine contraception (IUC) involves the use of an intra-uterine device (IUD), a highly effective, long-acting, reversible contraceptive method. Historically, the popularity of IUC has waxed and waned across different world regions, due to policy choices and shifts in public opinion. However, despite its advantages and cost-effectiveness for programmes, IUC's contribution to contraceptive prevalence is currently negligible in many countries. This paper presents the results of a systematic review of the global literature on provider and lay perspectives on IUC. It aims to shed light on the reasons for low use of IUC and reflect on potential opportunities for the method's promotion.
METHODS
A systematic search of the literature was conducted in four peer-reviewed journals and four electronic databases (MEDLINE, EMBASE, POPLINE, and Global Health). Screening resulted in the inclusion of 68 relevant publications.
RESULTS
Most included studies were conducted in areas where IUD use is moderate or low. Findings are similar across these areas. Many providers have low or uneven levels of knowledge on IUC and limited training. Many wrongly believe that IUC entails serious side effects such as pelvic inflammatory disease (PID), and are reluctant to provide it to entire eligible categories, such as HIV-positive women. There is particular resistance to providing IUC to teenagers and nulliparae. Provider opinions may be more favourable towards the hormonal IUD. Some health-care providers choose IUC for themselves. Many members of the public have low knowledge and unfounded misconceptions about IUC, such as the fear of infertility. Some are concerned about the insertion and removal processes, and about its effect on menses. However, users of IUC are generally satisfied and report a number of benefits. Peers and providers exert a strong influence on women's attitudes.
CONCLUSION
Both providers and lay people have inaccurate knowledge and misconceptions about IUC, which contribute to explaining its low use. However, many reported concerns and fears could be alleviated through correct information. Concerted efforts to train providers, combined with demand creation initiatives, could therefore boost the method's popularity. Further research is needed on provider and lay perspectives on IUDs in low- and middle-income countries.
Topics: Adult; Contraception; Female; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Intrauterine Devices
PubMed: 28950913
DOI: 10.1186/s12978-017-0380-8 -
The Cochrane Database of Systematic... Aug 2017Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012.
OBJECTIVES
To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.
SEARCH METHODS
In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.
SELECTION CRITERIA
Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.
MAIN RESULTS
We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency. Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I = 0%, high-quality evidence). Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I = 0%, high-quality evidence). Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence). Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence).
AUTHORS' CONCLUSIONS
Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA was more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.
Topics: Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Estradiol; Female; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Mifepristone; Norpregnadienes; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Unsafe Sex
PubMed: 28766313
DOI: 10.1002/14651858.CD001324.pub5 -
Contraception Feb 2017Combined hormonal contraceptives (CHCs), containing estrogen and progestin, are associated with an increased risk of venous thromboembolism (VTE) and arterial... (Review)
Review
BACKGROUND
Combined hormonal contraceptives (CHCs), containing estrogen and progestin, are associated with an increased risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) compared with nonuse. Few studies have examined whether nonoral formulations (including the combined hormonal patch, combined vaginal ring and combined injectable contraceptives) increase the risk of thrombosis compared with combined oral contraceptives (COCs).
OBJECTIVES
The objectives were to examine the risk of VTE and ATE among women using nonoral CHCs compared to women using COCs.
METHODS
We searched the PubMed database for all English language articles published from database inception through May 2016. We included primary research studies that examined women using the patch, ring or combined injectables compared with women using levonorgestrel-containing or norgestimate-containing COCs. Outcomes of interest included VTE (deep venous thrombosis or pulmonary embolism) or ATE (acute myocardial infarction or ischemic stroke). We assessed the quality of each individual piece of evidence using the system developed by the United States Preventive Services Task Force.
RESULTS
Eight studies were identified that met inclusion criteria. Of seven analyses from six studies examining VTE among patch users compared with levonorgestrel- or norgestimate-containing COC users, two found a statistically significantly elevated risk among patch users (risk estimates 2.2-2.3), one found an elevated risk that did not meet statistical significance (risk estimate 2.0), and four found no increased risk. Of three studies examining VTE among ring users compared with levonorgestrel COC users, one found a statistically significantly elevated risk among patch users (risk estimate 1.9) and two did not. Two studies did not find an increased risk for ATE among women using the patch compared with norgestimate COCs. We did not identify any studies examining combined injectable contraceptives.
CONCLUSION
Limited Level II-2 good to fair evidence demonstrated conflicting results on whether women using the patch or the ring have a higher risk of VTE than women using COCs. Evidence did not demonstrate an increased risk of ATE among women using the patch. Overall, any potential elevated risk likely represents a small number of events on a population level. Additional studies with standard methodology are needed to further clarify any associations and better understand mechanisms of hormone-induced thrombosis among users of nonoral combined hormonal contraception.
Topics: Administration, Cutaneous; Adolescent; Adult; Contraceptive Devices, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Estrogens; Female; Humans; Levonorgestrel; Norgestrel; Progestins; Risk Factors; Thromboembolism; Venous Thromboembolism; Young Adult
PubMed: 27771476
DOI: 10.1016/j.contraception.2016.10.005 -
The Cochrane Database of Systematic... Apr 2018Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the endometrium.Historically, there has been some concern that using the antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous thromboembolic disease. This is an umbrella term for deep venous thrombosis (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots in the blood vessels in the lungs).
OBJECTIVES
To determine the effectiveness and safety of antifibrinolytic medications as a treatment for heavy menstrual bleeding.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registers in November 2017, together with reference checking and contact with study authors and experts in the field.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing antifibrinolytic agents versus placebo, no treatment or other medical treatment in women of reproductive age with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary review outcomes were menstrual blood loss (MBL), improvement in HMB, and thromboembolic events.
MAIN RESULTS
We included 13 RCTs (1312 participants analysed). The evidence was very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding, and poor reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA or Kabi) versus no treatment or placeboWhen compared with a placebo, antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per cycle, 95% CI -62.70 to -43.70; I² = 8%; 4 RCTs, participants = 565; moderate-quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; 3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11% of women improve without treatment, 43% to 63% of women taking antifibrinolytics will do so. There was no clear evidence of a difference between the groups in adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low-quality evidence). Only one thromboembolic event occurred in the two studies that reported this outcome.TXA versus progestogensThere was no clear evidence of a difference between the groups in mean blood loss measured using the Pictorial Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36; I² = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; I² = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that if 46% of women improve with progestogens, 61% to 83% of women will do so with TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to 0.94; I² = 28%; 4 RCTs, participants = 349; low-quality evidence). No thromboembolic events were reported in any group.TXA versus non-steroidal anti-inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low-quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; 1 = 0%; 2 RCTs, participants = 161; low-quality evidence). This suggests that if 61% of women improve with NSAIDs, 71% to 100% of women will do so with TXA. Adverse events were uncommon and no comparative data were available. No thromboembolic events were reported.TXA versus ethamsylateTXA was associated with reduced mean blood loss (MD 100 mL per cycle, 95% CI -141.82 to -58.18; 1 RCT, participants = 53; low-quality evidence), but there was insufficient evidence to determine whether the groups differed in rates of improvement (RR 1.56, 95% CI 0.95 to 2.55; 1 RCT, participants = 53; very low quality evidence) or withdrawal due to adverse events (RR 0.78, 95% CI 0.19 to 3.15; 1 RCT, participants = 53; very low quality evidence).TXA versus herbal medicines (Safoof Habis and Punica granatum)TXA was associated with a reduced mean PBAC score after three months' treatment (MD -23.90 pts per cycle, 95% CI -31.92 to -15.88; I² = 0%; 2 RCTs, participants = 121; low-quality evidence). No data were available for rates of improvement. TXA was associated with a reduced mean PBAC score three months after the end of the treatment phase (MD -10.40 points per cycle, 95% CI -19.20 to -1.60; I² not applicable; 1 RCT, participants = 84; very low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 2.25, 95% CI 0.74 to 6.80; 1 RCT, participants = 94; very low quality evidence). No thromboembolic events were reported.TXA versus levonorgestrel intrauterine system (LIUS)TXA was associated with a higher median PBAC score than TXA (median difference 125.5 points; 1 RCT, participants = 42; very low quality evidence) and a lower likelihood of improvement (RR 0.43, 95% CI 0.24 to 0.77; 1 RCT, participants = 42; very low quality evidence). This suggests that if 85% of women improve with LIUS, 20% to 65% of women will do so with TXA. There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 0.83, 95% CI 0.25 to 2.80; 1 RCT, participants = 42; very low quality evidence). No thromboembolic events were reported.
AUTHORS' CONCLUSIONS
Antifibrinolytic treatment (such as TXA) appears effective for treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies, but may be less effective than LIUS. There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events, and most studies did not specifically include thromboembolism as an outcome.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Ethamsylate; Female; Hemostatics; Humans; Intrauterine Devices, Medicated; Lythraceae; Menorrhagia; Norethindrone; Plant Extracts; Progestins; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 29656433
DOI: 10.1002/14651858.CD000249.pub2