Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality: A Systematic Review and Meta-analysis

Importance: As many as 10% of women experience natural menopause by the age of 45 years. If confirmed, an increased risk of cardiovascular disease (CVD) and all-cause mortality associated with premature and early-onset menopause could be an important factor affecting risk of disease and mortality among middle-aged and older women. Objective: To systematically review and meta-analyze studies evaluating the effect of age at onset of menopause and duration since onset of menopause on intermediate CVD end points, CVD outcomes, and all-cause mortality. Data Sources: Medical databases (ie, Medline, EMBASE, and Web of Science) until March 2015. Study Selection: Studies (ie, observational cohort, case-control, or cross-sectional) that assessed age at onset of menopause and/or time since onset of menopause as exposures as well as risk of cardiovascular outcomes and intermediate CVD end points in perimenopausal, menopausal, or postmenopausal women. Data Extraction and Synthesis: Studies were sought if they were observational cohort, case-control, or cross-sectional studies; reported on age at onset of menopause and/or time since onset of menopause as exposures; and assessed associations with risk of CVD-related outcomes, all-cause mortality, or intermediate CVD end points. Data were extracted by 2 independent reviewers using a predesigned data collection form. The inverse-variance weighted method was used to combine relative risks to produce a pooled relative risk using random-effects models to allow for between-study heterogeneity. Main Outcomes and Measures: Cardiovascular disease outcomes (ie, composite CVD, fatal and nonfatal coronary heart disease [CHD], and overall stroke and stroke mortality), CVD mortality, all-cause mortality, and intermediate CVD end points. Results: Of the initially identified references, 32 studies were selected that included 310 329 nonoverlapping women. Outcomes were compared between women who experienced menopause younger than 45 years and women 45 years or older at onset; the relative risks (95% CIs) were 1.50 (1.28-1.76) for overall CHD, 1.11 (1.03-1.20) for fatal CHD, 1.23 (0.98-1.53) for overall stroke, 0.99 (0.92-1.07) for stroke mortality, 1.19 (1.08-1.31) for CVD mortality, and 1.12 (1.03-1.21) for all-cause mortality. Outcomes were also compared between women between 50 and 54 years at onset of menopause and women younger than 50 years at onset; there was a decreased risk of fatal CHD (relative risk, 0.87; 95% CI, 0.80-0.96) and no effect on stroke. Time since onset of menopause in relation to risk of developing intermediate cardiovascular traits or CVD outcomes was reported in 4 observational studies with inconsistent results. Conclusions and Relevance: The findings of this review indicate a higher risk of CHD, CVD mortality, and overall mortality in women who experience premature or early-onset menopause.This study was sponsored and funded by Metagenics

Continuous Radar Tracking Illustrates the Development of Multi-destination Routes of Bumblebees

Animals that visit multiple foraging sites face a problem, analogous to the Travelling Salesman Problem, of finding an efficient route. We explored bumblebees’ route development on an array of five artificial flowers in which minimising travel distances between individual feeders conflicted with minimising overall distance. No previous study of bee spatial navigation has been able to follow animals’ movement during learning; we tracked bumblebee foragers continuously, using harmonic radar, and examined the process of route formation in detail for a small number of selected individuals. On our array, bees did not settle on visit sequences that gave the shortest overall path, but prioritised movements to nearby feeders. Nonetheless, flight distance and duration reduced with experience. This increased efficiency was attributable mainly to experienced bees reducing exploration beyond the feeder array and flights becoming straighter with experience, rather than improvements in the sequence of feeder visits. Flight paths of all legs of a flight stabilised at similar rates, whereas the first few feeder visits became fixed early while bees continued to experiment with the order of later visits. Stabilising early sections of a route and prioritising travel between nearby destinations may reduce the search space, allowing rapid adoption of efficient routes