New findings indicate that women who experience menopause later in life possess healthier blood vessels and mitochondria, along with a distinct profile of blood metabolites compared to those who undergo menopause earlier. This study clarifies why having a later onset of menopause correlates with a reduced risk of heart attacks and strokes.
According to new research from the University of Colorado Boulder, women who undergo menopause later tend to retain healthier blood vessels for many years compared to those who transition earlier.
Published in the American Heart Association’s journal Circulation Research, this study provides valuable insights into why women who stop menstruating at age 55 or older are noticeably less prone to experiencing heart attacks and strokes in their postmenopausal life.
Timed perfectly with Women’s Heart Health Month in February, these results might pave the way for novel interventions, including dietary changes, to help mitigate heart disease risks—the leading cause of death among women.
“Our research reveals that later-onset menopause has actual physiological advantages, and it’s among the first studies to pinpoint the specific mechanisms that contribute to these benefits,” stated Sanna Darvish, a PhD candidate in the Department of Integrative Physiology.
Heart disease affects nearly half of women in the U.S., causing about one in five deaths annually. Although women are less likely to die from heart attacks or strokes than men throughout most of their lives, their risk significantly increases and surpasses that of men after menopause.
However, there is an important exception to this pattern.
Prior research indicates that women who experience menopause—defined as going an entire year without a menstrual period—at 55 or later have a 20% lower chance of developing heart disease compared to those whose menopause occurs between the ages of 45 and 54.
To investigate the reasons behind this, Darvish and her team at CU’s Integrative Physiology of Aging Laboratory examined the vascular health of 92 women, focusing on brachial artery flow-mediated dilation (FMD), which reflects how well the primary blood vessel in the upper arm expands in response to increased blood flow.
The researchers also evaluated the health of the women’s mitochondria—the energy-generating structures in the cells lining their blood vessels—and analyzed the different molecules present in their bloodstream.
As anticipated, all postmenopausal participants displayed significantly poorer arterial function compared to their premenopausal counterparts. This deterioration is partly due to the natural decrease in nitric oxide production, a compound that facilitates blood vessel dilation and helps prevent stiffness and plaque buildup. Additionally, aging mitochondria in blood vessel cells become less effective and produce more harmful free radicals, as explained by Darvish.
Increased Risk
The onset of menopause exacerbates the age-related decline in vascular health. However, the study revealed that approximately 10% of women experiencing late-onset menopause appear somewhat shielded from this decline, according to senior author Matthew Rossman.
For example, vascular health was found to be only 24% worse in those with late-onset menopause compared to the premenopausal group, while the early menopause group had 51% worse vascular health.
Astonishingly, these differences between the two groups persisted for five or more years post-menopause. Women with late-onset menopause retained 44% better vascular function compared to their counterparts with earlier menopause.
This preserved vascular health among the late-onset group was associated with better functioning mitochondria that produced fewer free radicals. Furthermore, the blood of the two groups displayed distinct characteristics, with the late-onset group exhibiting healthier levels of 15 different lipid-related metabolites.
“Our findings indicate that women who experience menopause later have a kind of natural protection against vascular dysfunction caused by oxidative stress over time,” noted Rossman, an assistant research professor in the Department of Integrative Physiology.
Further research is needed to elucidate the precise factors contributing to this protection, with the researchers speculating that improved mitochondrial function and specific blood-circulating lipids may be involved.
Next steps for the team include examining how early-onset menopause affects heart health and assessing whether nutritional supplements that counteract free radicals in blood vessels can lower heart disease risks in women who are more vulnerable.
In a related study, Rossman found initial evidence indicating that MitoQ—a modified form of the antioxidant Coenzyme Q10 designed for mitochondrial targeting—remarkably reversed blood vessel aging within weeks in both male and female subjects. A larger clinical trial is currently underway.
“We aspire for this research to highlight age at menopause as a significant female-specific risk factor that should be more discussed among women and their healthcare providers,” expressed Darvish.
