Later-onset menopause linked to healthier blood vessels, lower heart disease risk

(Press-News.org) Women who go through menopause later in life have healthier blood vessels for years to come than those who go through it earlier, according to new University of Colorado Boulder research.

The study, published in the American Heart Association journal Circulation Research, offers new insight into why females who stop menstruating at age 55 or later are significantly less likely to have heart attacks and strokes in their postmenopausal years. 

Arriving just in time for Women's Heart Health Month, in February, the findings could help lead to new therapies, including dietary interventions, to reduce risk of heart disease — the No. 1  killer of women.

“Our paper identifies that there’s actually a physiological benefit to later-onset menopause and is one of the first to identify the specific mechanisms driving these benefits,” said first author Sanna Darvish, a PhD candidate in the Department of Integrative Physiology. 

Nearly half of women in the U.S. live with heart disease and it accounts for about one in five female deaths each year. While females are less likely to die of a heart attack or stroke than males for most of their life, their risk spikes and overtakes male risk after menopause.

But there is one notable caveat to this trend.

Previous studies show that women who hit menopause—defined as going one year without a period— at age 55 or later are as much as 20% less likely to develop heart disease than those who cease menstruation at the usual 45 to 54 years old.

Darvish and her colleagues at CU’s Integrative Physiology of Aging Laboratory set out to determine why. They assessed the vascular health of 92 women, looking specifically at a measure called brachial artery flow-mediated dilation (FMD), or how well their brachial artery — the main blood vessel in the upper arm — dilates with increased blood flow. 

The team also measured the health of the women’s mitochondria, the energy powerhouses in the cells lining their blood vessels. And they took a close look at what molecules were coursing through their bloodstreams.

Not surprisingly, all the postmenopausal women had significantly worse arterial function than their premenopausal counterparts. That’s in part because, as people age, they produce less nitric oxide, a compound that helps blood vessels dilate and keeps them from getting stiff and developing plaque. Mitochondria in cells lining the blood vessels also become dysfunctional with age and generate more damaging molecules called free radicals, explained Darvish.

A spike in risk

When menopause hits, the age-related decline in vascular health accelerates. But the 10% or so of women who experience late-onset menopause appear to be somewhat protected from this effect, said senior author Matthew Rossman.

For instance, the study found that vascular function was only 24% worse in the late-onset menopause group compared to the premenopausal group, while those in the normal-onset group had 51% worse vascular health. 

Remarkably, such differences between the groups persisted five years or more after the women went through menopause, with the late-onset group still having 44% better vascular function than the normal onset group.

Preserved vascular health in the late-onset group was related to better functioning of mitochondria which produced fewer free radicals, the study found. The circulating blood of the two groups also looked different, with the late-onset group showing “more favorable” levels of 15 different lipid or fat-related metabolites in their blood. 

“Our data suggest that women who complete menopause at a later age have a kind of natural inherent protection from vascular dysfunction that can come from oxidative stress over time,” said Rossman, an assistant research professor in the Department of Integrative Physiology.

More research is necessary to determine exactly what drives that protection, but the researchers suspect better mitochondrial function and certain lipids circulating in their blood may play a role.

Next, the team plans to explore how early-onset menopause might impact heart health and whether nutritional supplements aimed at neutralizing free radicals inside blood vessels might reduce heart disease risk in women who are at greater risk.

In one previous study, Rossman found initial evidence that MitoQ— a chemically altered version of the antioxidant Coenzyme Q10 that targets mitochondria— reversed blood vessel aging significantly within weeks in male and female subjects. A larger clinical trial is now underway.

“We hope this work puts age at menopause on the map as a female-specific risk factor that women and their doctors discuss more,” said Darvish. 

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