Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality

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.

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.