Menopausal hormone therapy and women's health: An umbrella review.

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

The Use of Low-Level Laser Therapy to Reduce Postoperative Morbidity After Third Molar Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: Surgical removal of third molars carries morbidity and significantly affects patients' quality-of-life. This study aims to investigate whether administration of low-level laser therapy (LLLT) is effective in reducing postoperative morbidity in patients undergoing surgical removal of mandibular third molars compared with placebo. MATERIAL AND METHODS: A systematic review and meta-analysis involving a comprehensive search strategy implemented across 5 electronic databases. This was supplemented by hand searching and contacting international experts and grey literature. Titles, abstracts, and full articles were scrutinized for studies meeting the inclusion criteria. All randomized controlled trials comparing treatment group of LLLT with a placebo control group were eligible for inclusion. The outcomes variables were postoperative pain, swelling, and trismus. Risk of bias and methodological quality assessment was carried out. We pooled data statistically, and meta-analyses were carried out using a random-effects model. RESULTS: Seventeen randomized controlled trials were included in this systematic review, all of which were considered to have a low risk of bias. Participants, aged 13 to 70 years, and 35% women, totaled 1064. Meta-analyses found significant reductions in standardized mean differences (SMDs) in swelling at day 2 and day 7 postoperatively (SMD, -0.611; 95% confidence interval, -0.968, -0.234 and SMD, -0.532; 95% confidence interval, -0.795, -0.269). There were nonsignificant reductions in SMD in pain and trismus at day 2 and day 7 postoperatively. CONCLUSIONS: LLLT significantly reduces swelling after extraction of mandibular third molars compared with placebo. LLLT has not shown to reduce postoperative pain and trismus. LLLT does not cause adverse effects. There is currently insufficient evidence available, to promote the investment in LLLT vs the net clinical benefit. Randomized controlled trials with larger sample size and standardized study design and outcome measures are required, to make definitive recommendations to clinicians on its use on patients.

Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis.

BACKGROUND: Smoke-free legislation has the potential to reduce the substantive disease burden associated with second-hand smoke exposure, particularly in children. We investigated the effect of smoke-free legislation on perinatal and child health. METHODS: We searched 14 online databases from January, 1975 to May, 2013, with no language restrictions, for published studies, and the WHO International Clinical Trials Registry Platform for unpublished studies. Citations and reference lists of articles of interest were screened and an international expert panel was contacted to identify additional studies. We included studies undertaken with designs approved by the Cochrane Effective Practice and Organisation of Care that reported associations between smoking bans in workplaces, public places, or both, and one or more predefined early-life health indicator. The primary outcomes were preterm birth, low birthweight, and hospital attendances for asthma. Effect estimates were pooled with random-effects meta-analysis. This study is registered with PROSPERO, number CRD42013003522. FINDINGS: We identified 11 eligible studies (published 2008-13), involving more than 2·5 million births and 247,168 asthma exacerbations. All studies used interrupted time-series designs. Five North American studies described local bans and six European studies described national bans. Risk of bias was high for one study, moderate for six studies, and low for four studies. Smoke-free legislation was associated with reductions in preterm birth (four studies, 1,366,862 individuals; -10·4% [95% CI -18·8 to -2·0]; p=0·016) and hospital attendances for asthma (three studies, 225,753 events: -10·1% [95% CI -15·2 to -5·0]; p=0·0001). No significant effect on low birthweight was identified (six studies, >1·9 million individuals: -1·7% [95% CI -5·1 to 1·6]; p=0·31). INTERPRETATION: Smoke-free legislation is associated with substantial reductions in preterm births and hospital attendance for asthma. Together with the health benefits in adults, this study provides strong support for WHO recommendations to create smoke-free environments. FUNDING: Thrasher Fund, Lung Foundation Netherlands, International Paediatric Research Foundation, Maastricht University, Commonwealth Fund.

The impact of smoke-free legislation on fetal, infant and child health: a systematic review and meta-analysis protocol.

INTRODUCTION: Second-hand smoke (SHS) exposure is estimated to kill 600 000 people worldwide annually. The WHO recommends that smoke-free indoor public environments are enforced through national legislation. Such regulations have been shown to reduce SHS exposure and, consequently, respiratory and cardiovascular morbidity. Evidence of particular health benefit in children is now emerging, including reductions in low birthweight deliveries, preterm birth and asthma exacerbations. We aim to comprehensively assess the impact of smoke-free legislation on fetal, infant and childhood outcomes. This can inform further development and implementation of global policy and strategies to reduce early life SHS exposure. METHODS: Two authors will search online databases (1975-present; no language restrictions) of published and unpublished/in-progress studies, and references and citations to articles of interest. We will consult experts in the field to identify additional studies. Studies should describe associations between comprehensive or partial smoking bans in public places and health outcomes among children (0-12 years): stillbirth, preterm birth, low birth weight, small for gestational age, perinatal mortality, congenital anomalies, bronchopulmonary dysplasia, upper and lower respiratory infections and wheezing disorders including asthma. The Cochrane Effectiveness Practice and Organisational Care (EPOC)-defined study designs are eligible. Study quality will be assessed using the Cochrane 7-domain-based evaluation for randomised and clinical trials, and EPOC criteria for quasiexperimental studies. Data will be extracted by two reviewers and presented in tabular and narrative form. Meta-analysis will be undertaken using random-effects models, and generic inverse variance analysis for adjusted effect estimates. We will report sensitivity analyses according to study quality and design characteristics, and subgroup analyses according to coverage of ban, age group and parental/maternal smoking status. Publication bias will be assessed. ETHICS AND DISSEMINATION: Ethics assessment is not required. RESULTS: Will be presented in one manuscript. The protocol is registered with PROSPERO, registration number CRD42013003522.