Menopausal hormone therapy and women’s health: An umbrella review

BackgroundThere 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 findingsWe 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).ConclusionsMHT 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.

In an umbrella review, Guo-Qiang Zhang and colleagues comprehensively summarize evidence on the benefits and harms of menopausal hormone therapy across diverse health outcomes.     

Lower-body power,linear speed,and change-of-direction speed in Division I collegiate women’s volleyball players

Volleyball players need to sprint and change direction during a match. Lower-body power, often measured by jump tests, could contribute to faster movements. How different jumps relate to linear and change-of-direction (COD) speed has not been analyzed in Division I (DI) collegiate women’s volleyball players. Fifteen female volleyball players completed the vertical jump (VJ), two-step approach jump (AppJ), and standing broad jump (SBJ). Peak power and power-to-body mass ratio (P:BM) were derived from VJ and AppJ height; relative SBJ was derived from SBJ distance. Linear speed was measured via a 20-m sprint (0–10 and 0–20 m intervals); COD speed was measured using the pro-agility shuttle. Pearson’s correlations (p < 0.05) calculated relationships between the power variables, and speed tests. There were no significant relationships between the power variables and the 0–10 m sprint interval. Greater VJ height (r = -0.534) and P:BM (r = -0.557) related to a faster 0–20 m sprint interval. This be due to a greater emphasis on the stretch-shortening cycle to generate speed over 20 m. However, although a 20-m sprint may provide a measure of general athleticism, the distance may not be specific to volleyball. This was also indicated as the AppJ did not relate to any of the speed tests. Nonetheless, VJ height and P:BM, and SBJ distance and relative SBJ, all negatively correlated with the proagility shuttle (r = -0.548 to -0.729). DI women’s collegiate volleyball players could develop absolute and relative power in the vertical and horizontal planes to enhance COD speed.     

Examining the Ugandan health system’s readiness to deliver rheumatic heart disease-related services

BackgroundIn 2018, the World Health Assembly mandated Member States to take action on rheumatic heart disease (RHD), which persists in countries with weak health systems. We conducted an assessment of the current state of RHD-related healthcare in Uganda.Methodology/Principal findingsThis was a mixed-methods, deductive simultaneous design study conducted in four districts of Uganda. Using census sampling, we surveyed health facilities in each district using an RHD survey instrument that was modeled after the WHO SARA tool. We interviewed health workers with experience managing RHD, purposively sampling to ensure a range of qualification and geographic variation. Our final sample included 402 facilities and 36 health workers. We found major gaps in knowledge of clinical guidelines and availability of diagnostic tests. Antibiotics used in RHD prevention were widely available, but cardiovascular medications were scarce. Higher levels of service readiness were found among facilities in the western region (Mbarara district) and private facilities. Level III health centers were the most prepared for delivering secondary prevention. Health worker interviews revealed that limited awareness of RHD at the district level, lack of diagnostic tests and case management registries, and absence of clearly articulated RHD policies and budget prioritization were the main barriers to providing RHD-related healthcare.Conclusions/SignificanceUganda’s readiness to implement the World Health Assembly RHD Resolution is low. The forthcoming national RHD strategy must focus on decentralizing RHD diagnosis and prevention to the district level, emphasizing specialized training of the primary healthcare workforce and strengthening supply chains of diagnostics and essential medicines.     

Islamic preaching and women’s spectatorship in West Java

In the urban villages of Bandung, the capital city of the Indonesian province of West Java, many Muslim women routinely attend between four and six oratorical and/or pedagogical events per week. This article analyses this participation by observing the forms and patterns of these women’s spectatorship, specifically observing their mobility, the interaction between their life‐cycles and their participation habits, the gendered embodiment of Islamic knowledge they display, the effect of hegemonic masculinities, and preaching performances which treat them not only as Muslims intent on increasing their Islamic knowledge, but also as pleasure‐taking subjects. The article concludes that the conduct and management of preaching events intended for mixed audiences are highly sensitive to women’s spectatorship and warns against the assumption that Islamic practice is a punishing sphere of patriarchy. In fact, when the influence of women’s spectatorship on the conduct and management of such preaching events is appreciated, West Java’s preaching events appear as a feminised domain.     

Associations between women’s empowerment and child development,growth, and nurturing care practices in sub-Saharan Africa: A cross-sectional analysis of demographic and health survey data

BackgroundApproximately 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Women’s empowerment may help provide inputs of nurturing care for early development and growth by building caregiver capacity and family support. We examined the associations between women’s empowerment and child development, growth, early learning, and nutrition in sub-Saharan Africa (SSA).Methods and findingsWe pooled data on married women (15 to 49 years) and their children (36 to 59 months) from Demographic and Health Surveys that collected data on child development (2011 to 2018) in 9 SSA countries (N = 21,434): Benin, Burundi, Cameroon, Chad, Congo, Rwanda, Senegal, Togo, and Uganda. We constructed a women’s empowerment score using factor analysis and assigned women to country-specific quintile categories. The child outcomes included cognitive, socioemotional, literacy–numeracy, and physical development (Early Childhood Development Index), linear growth (height-for-age Z-score (HAZ) and stunting (HAZ <−2). Early learning outcomes were number of parental stimulation activities (range 0 to 6) and learning resources (range 0 to 4). The nutrition outcome was child dietary diversity score (DDS, range 0 to 7). We assessed the relationship between women’s empowerment and child development, growth, early learning, and nutrition using multivariate generalized linear models.On average, households in our sample were large (8.5 ± 5.7 members) and primarily living in rural areas (71%). Women were 31 ± 6.6 years on average, 54% had no education, and 31% had completed primary education. Children were 47 ± 7 months old and 49% were female. About 23% of children had suboptimal cognitive development, 31% had suboptimal socioemotional development, and 90% had suboptimal literacy–numeracy development. Only 9% of children had suboptimal physical development, but 35% were stunted. Approximately 14% of mothers and 3% of fathers provided ≥4 stimulation activities. Relative to the lowest quintile category, children of women in the highest empowerment quintile category were less likely to have suboptimal cognitive development (relative risk (RR) 0.89; 95% confidence interval (CI) 0.80, 0.99), had higher HAZ (mean difference (MD) 0.09; 95% CI 0.02, 0.16), lower risk of stunting (RR 0.93; 95% CI 0.87, 1.00), higher DDS (MD 0.17; 95% CI 0.06, 0.29), had 0.07 (95% CI 0.01, 0.13) additional learning resources, and received 0.16 (95% CI 0.06, 0.25) additional stimulation activities from their mothers and 0.23 (95% CI 0.17 to 0.29) additional activities from their fathers. We found no evidence that women’s empowerment was associated with socioemotional, literacy–numeracy, or physical development. Study limitations include the possibility of reverse causality and suboptimal assessments of the outcomes and exposure.ConclusionsWomen’s empowerment was positively associated with early child cognitive development, child growth, early learning, and nutrition outcomes in SSA. Efforts to improve child development and growth should consider women’s empowerment as a potential strategy.

Lilia Bliznashka and co-workers study empowerment of women and associated child health outcomes in sub-Saharan Africa.     

The Bloom’s and Werner’s syndrome proteins are DNA structure-specific helicases

BLM and WRN, the products of the Bloom’s and Werner’s syndrome genes, are members of the RecQ family of DNA helicases. Although both have been shown previously to unwind simple, partial duplex DNA substrates with 3′→5′ polarity, little is known about the structural features of DNA that determine the substrate specificities of these enzymes. We have compared the substrate specificities of the BLM and WRN proteins using a variety of partial duplex DNA molecules, which are based upon a common core nucleotide sequence. We show that neither BLM nor WRN is capable of unwinding duplex DNA from a blunt-ended terminus or from an internal nick. However, both enzymes efficiently unwind the same blunt-ended duplex containing a centrally located 12 nt single-stranded ‘bubble’, as well as a synthetic X-structure (a model for the Holliday junction recombination intermediate) in which each ‘arm’ of the 4-way junction is blunt-ended. Surprisingly, a 3′-tailed duplex, a standard substrate for 3′→5′ helicases, is unwound much less efficiently by BLM and WRN than are the bubble and X-structure substrates. These data show conclusively that a single-stranded 3′-tail is not a structural requirement for unwinding of standard B-form DNA by these helicases. BLM and WRN also both unwind a variety of different forms of G-quadruplex DNA, a structure that can form at guanine-rich sequences present at several genomic loci. Our data indicate that BLM and WRN are atypical helicases that are highly DNA structure specific and have similar substrate specificities. We interpret these data in the light of the genomic instability and hyper-recombination characteristics of cells from individuals with Bloom’s or Werner’s syndrome.     

Special Issue Editor’s choice: Global child health from birth to adolescence and beyond

Caitlin Moyer discusses PLOS Medicine’s Special Issue on Global Child and Adolescent Health.

In a new PLOS Medicine special issue, entitled “Global Child and Adolescent Health: From Birth to Adolescence and Beyond”, guest editors Zulfiqar Bhutta, Quique Bassat, and Kathryn Yount bring to the forefront new research to illuminate global challenges for achievement of child and adolescent health and survival goals, and novel ways to address these challenges. The research articles in this special issue cover a broad range of current threats to child and adolescent health and wellbeing around the globe, shining a spotlight on the health impacts of pollutions, climate change, injury, violence, infectious diseases, undernutrition, and adolescent pregnancy. It is important to identify the gaps in knowledge that stand in the way of ensuring that all children and adolescents have the opportunity to survive, grow, and achieve developmental, social, and academic milestones. These studies further this goal by investigating new strategies that may be adopted to address these areas of need.     

Birth cohort relative to an influenza A virus’s antigenic cluster introduction drives patterns of children’s antibody titers

An individual’s antibody titers to influenza A strains are a result of the complicated interplay between infection history, cross-reactivity, immune waning, and other factors. It has been challenging to disentangle how population-level patterns of humoral immunity change as a function of age, calendar year, and birth cohort from cross-sectional data alone. We analyzed 1,589 longitudinal sera samples from 260 children across three studies in Nicaragua, 2006–16. Hemagglutination inhibition (HAI) titers were determined against four H3N2 strains, one H1N1 strain, and two H1N1pdm strains. We assessed temporal patterns of HAI titers using an age–period–cohort modeling framework. We found that titers against a given virus depended on calendar year of serum collection and birth cohort but not on age. Titer cohort patterns were better described by participants’ ages relative to year of likely introduction of the virus’s antigenic cluster than by age relative to year of strain introduction or by year of birth. These cohort effects may be driven by a decreasing likelihood of early-life infection after cluster introduction and by more broadly reactive antibodies at a young age. H3N2 and H1N1 viruses had qualitatively distinct cohort patterns, with cohort patterns of titers to specific H3N2 strains reaching their peak in children born 3 years prior to that virus’s antigenic cluster introduction and with titers to H1N1 and H1N1pdm strains peaking for children born 1–2 years prior to cluster introduction but not being dramatically lower for older children. Ultimately, specific patterns of strain circulation and antigenic cluster introduction may drive population-level antibody titer patterns in children.