Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed). RESULTS: We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I2  = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I2  = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I2  = 0%, P = .84). CONCLUSIONS: Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.

Tratamento farmacológico para insuficiência cardíaca sistólica crônica e as evidências disponíveis: uma revisão narrativa da literatura / Pharmacological treatment for chronic systolic heart failure and the available evidence: a narrative review of the literature

Introdução: A insuficiência cardíaca é uma síndrome clínica complexa de caráter sistêmico, definida como disfunção cardíaca que ocasiona inadequado suprimento sanguíneo para atender as necessidades metabólicas teciduais. É uma doença que se manifesta na maioria da população de forma crônica, progressiva e tem causa multifatorial. Caracteriza-se por internações frequentes, elevada prevalência, alta taxa de mortalidade e alto custo socioeconômico. O diagnóstico precoce e o tratamento efetivo são fundamentais no prognóstico desta síndrome. O tratamento medicamentoso visa diminuir a progressão da doença, reduzir mortalidade e hospitalização, aliviar sintomas e melhorar a qualidade de vida dos pacientes. Objetivo: Mapear as evidências sobre o tratamento farmacológico da insuficiência cardíaca crônica do tipo sistólica ou com fração de ejeção reduzida. Método: Revisão narrativa da literatura de ensaios clínicos randomizados e estudos observacionais. As seguintes bases de dados eletrônicas foram utilizadas: CENTRAL via Cochrane Library, MEDLINE via PubMed, LILACS via BVS e Embase via Elsevier. Como descritores, foram utilizados: insuficiência cardíaca, insuficiência cardíaca sistólica, tratamento medicamentoso, revisão, ensaio clínico. Resultados: Foi encontrado um total de 10.241 estudos nas diferentes bases de dados. Destes, os mais relevantes foram incluídos nesta revisão e os dados encontrados foram apresentados de forma narrativa. Conclusão: Os dados disponíveis demonstraram que o pilar do tratamento medicamentoso capaz de mudar a história natural da insuficiência cardíaca crônica inclui os moduladores do sistema renina-angiotensina-aldosterona e os bloqueadores dos receptores beta adrenégicos. Para melhorar sintomas e reduzir hospitalização, estão os diuréticos, a digoxina e a ivabradina.