Later Menopause is Associated With Healthier Blood Vessels and a Lower Risk of Heart Disease

Women who experience late menopause have healthier blood vessels for years afterward compared to women who experience early menopause, according to a new study from the University of Colorado Boulder. The study, published in the American Heart Association’s journal Circulation Research, offers new insights into why women who do not experience menstruation until the age of 55 or later are significantly less likely to suffer a heart attack or stroke in their postmenopausal years. The findings come just in time for Women’s Heart Health Month in February and could help develop new therapies, including dietary interventions, to reduce the risk of heart disease, the leading cause of death in women.

How Late Menopause Affects Female Heart Health

“Our work shows that late menopause does have a physiological benefit and is one of the first to identify the specific mechanisms by which it provides this benefit,” said first author Sanna Darvish, a doctoral candidate in the Department of Integrative Physiology. While women are less likely than men to die from a heart attack or stroke for most of their lives, their risk skyrockets after menopause and exceeds that of men. However, this trend is associated with a caveat. Previous studies show that women who reach menopause – defined as one year without a period – at age 55 or older are 20% less likely to develop heart disease than women who stop menstruating at the usual age of 45 to 54.

Darvish and her colleagues at CU’s Integrative Physiology of Aging Lab wanted to find out why. They examined the vascular health of 92 women, looking in particular at a measurement called brachial arterial flow-mediated dilation (FMD), i.e. how well their brachial artery – the main blood vessel in the upper arm – dilates when blood flow increases. The team also examined the state of the women’s mitochondria, the energy-producing power plants in the cells that line their blood vessels. And they took a close look at the molecules flowing through their bloodstreams.

Not surprisingly, all postmenopausal women had significantly worse arterial function than their premenopausal peers. This is partly because as people age, they produce less nitric oxide, a compound that helps blood vessels dilate and keeps them from stiffening and developing plaque. The mitochondria in the cells that line blood vessels also become dysfunctional with age, creating more damaging molecules called free radicals, Darvish explained.

A Natural Defense Against Vascular Dysfunction

When menopause sets in, the age-related decline in vascular health accelerates. But the approximately 10% of women who experience late-onset menopause appear to be somewhat protected from this effect, according to lead author Matthew Rossman. The study found, for example, that vascular function in the late-onset menopause group was only 24% worse than in the premenopausal women, while vascular health in the normal-onset menopause group was 51% worse.

Remarkably, such differences between the groups persisted for five years or more after the women entered menopause, with the late-onset menopause group still showing 44% better vascular function than the normal-onset menopause group. The preserved vascular health in the late-onset group was linked to better mitochondrial function, which produced fewer free radicals, according to the study. The circulating blood of the two groups also looked different, with the late-onset group having “more favorable” levels of 15 different lipid or fat-related metabolites in the blood. These data suggest that women who experience menopause at an older age have a kind of natural protection against vascular dysfunction that can develop over time due to oxidative stress.

Further research is needed to determine exactly what provides this protection, but the researchers suspect that better mitochondrial function and certain lipids circulating in the blood may play a role. Next, the team wants to study how early menopause might affect heart health and whether supplements that aim to neutralize free radicals in blood vessels could reduce the risk of heart disease in women at increased risk. In an earlier study, Rossman found preliminary evidence that MitoQ – a chemically modified version of the antioxidant coenzyme Q10 that targets mitochondria – significantly reversed blood vessel aging in both male and female subjects within a few weeks. A larger clinical trial is currently underway.