Early-Onset Menopause Means Greater CV-Event Risk Later

Larry Hand

September 16, 2016

ROTTERDAM, THE NETHERLANDS — Women who experience premature or early-onset menopause when younger than 45 carry an increased risk of adverse cardiovascular outcomes, according to new research[1].

"Our study shows that age at menopause might be a predictor of future cardiovascular events and mortality in postmenopausal women; so women with early onset of menopause are at increased risk of heart disease," Dr Taulant Muka (Erasmus University, Rotterdam, the Netherlands) told heartwire from Medscape by email.

"These findings suggest that women with early onset of menopause may be a group to target for proactive cardiovascular prevention strategies," he said.

Muka and colleagues conducted a systematic review and meta-analysis of published studies looking into the effect of age on onset of menopause and duration since menopause onset on intermediate cardiovascular-disease outcomes and all-cause mortality. They included 32 studies involving 310,329 nonoverlapping women in their analysis.

The studies compared outcomes for women who experienced menopause younger than 45 with outcomes for women 45 and older, as well as outcomes for women younger than 50 at menopause onset with outcomes for women 50 to 54 years old.

The researchers found that the relative risks for women who experienced menopause onset younger than 45, compared with women 45 or older at onset, came to 1.50 for overall coronary heart disease (CHD), 1.11 for fatal CHD, 1.23 for overall stroke, 0.99 for stroke mortality, 1.19 for CVD mortality, and 1.12 for all-cause mortality.

For women 50 to 54 years old at menopause onset, the researchers found a decreased risk of fatal CHD (RR 0.87) and no effect on stroke.

"Efforts to increase public awareness among women who experience menopause before age 45 may result in reducing the risk of cardiovascular disease," Muka told heartwire . "Our results indicate that menopause might be a critical period to evaluate women's risk for future cardiovascular events and that it may be an appropriate time to introduce interventions to reduce the risk."

"Women going into menopause before age 45 may consider a control for medical conditions such as hypertension, dyslipidemia, insulin resistance, and other cardiometabolic risk factors, since it may help them to identify whether they are at high risk for developing cardiovascular disease and profit from lifestyle or pharmacological interventions," he added.

In an editor's note[2], Dr Elizabeth McNally (Northwestern University, Chicago, IL) writes that age at menopause onset is under genetic influence and that a broad expression pattern of related genes suggests that direct molecular mechanisms "may be the tie to cardiovascular disease, as defective DNA repair can alter immune and vascular health."

In an invited commentary[3], Dr JoAnn E Manson (Harvard Medical School, Boston, MA) and D. Teresa K Woodruff (Northwestern University), write, "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."

This study was sponsored and funded by Metagenics. Muka received research support from Metagenics. Disclosures for the coauthors are listed in the article.

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