Early onset menopause may increase heart and mortality risk

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menopausewebWomen who experienced premature or early-onset menopause appeared to have a greater risk of coronary heart disease (CHD), cardiovascular disease (CVD) mortality, and all-cause mortality but no association with stroke risk.

In a new study, Dr Taulant Muka, of Erasmus University Medical Centre, Rotterdam, the Netherlands and colleagues evaluated the effect of age at onset of menopause and duration since onset of menopause on certain cardiovascular disease (CVD) outcomes 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 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 examine this issue, the researchers conducted a systematic review and meta-analysis of 32 studies (310,329 women) that met criteria for inclusion in the study.

Outcomes were compared between women who experienced menopause younger than 45 years and women 45 years or older at onset. The researchers found that overall, women who experienced premature or early-onset menopause appeared to have a greater risk of coronary heart disease (CHD), CVD mortality, and all-cause mortality but no association with stroke risk. Women between 50 and 54 years at onset of menopause had a decreased risk of fatal CHD compared with women younger than 50 years at onset.

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.

“The findings of this review indicate a higher risk of CHD, cardiovascular mortality, and overall mortality in women who experience premature or early-onset menopause when younger than 45 years. However, this review also highlights important gaps in the existing literature and calls for further research to reliably establish whether cardiovascular risk varies in relation to the time since onset of menopause and the mechanisms leading early menopause to cardiovascular outcomes and mortality,” the authors write.

Early menopause serves as a sentinel for elevated CVD risk, write Dr JoAnn E Manson, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and Dr Teresa K Woodruff, of Northwestern University, Chicago, in an accompanying commentary.

“The recognition that women with early reproductive decline constitute a population at increased vascular risk provides important opportunities for early intervention in terms of both risk factor modification and, when appropriate, hormonal treatment. Although additional research is needed to clarify the complex associations between accelerated reproductive aging and vascular health, applying current knowledge will help to reduce cardiovascular events in this high-risk patient population.”

Abstract
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.

Authors
Taulant Muka; Clare Oliver-Williams; Setor Kunutsor; Joop SE Laven; Bart CJM Fauser; Rajiv Chowdhury; Maryam Kavousi; Oscar H Franco

JAMA material
JAMA Cardiology abstract
JAMA Cardiology invited commentary
JAMA Cardiology editorial


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