Later-Onset Menopause Associated With a Lower Risk of Heart Disease, Study Finds

Research findings published in the American Heart Association’s journal, Circulation Research, show that women with late-onset menopause tend to have healthier blood vessels compared to women who go through it earlier. Because the blood vessels are healthier, these women are significantly less likely to have heart attacks or strokes in their postmenopausal years, according to the authors.¹

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Previously, it was known that postmenopausal women who complete menopause at a later age (≥ 55 years) have a lower risk of cardiovascular disease compared with those who complete menopause at a normal age (45-54 years). Despite this knowledge, the association between menopause and vascular endothelial dysfunction was not known. Additionally, it was unknown how the mechanisms of later age at menopause may modulate endothelial function, if at all.¹

For this study, the investigators measured endothelial function (defined as brachial artery flow-mediated dilation [FMD_BA]) in age-matched late- and normal-onset postmenopausal women. Additionally, a younger premenopausal group was enrolled as a reference. The investigators determined mitochondrial reactive oxygen species (mitoROS)-related suppression of endothelial function (defined as the change in FMD_BA with an acute dose of the mitochondria-targeted antioxidant MitoQ; ΔFMD_{BA, MTQ}) in the enrolled women.

Further, the effects of serum from late- and normal-onset postmenopausal women on mitoROS bioactivity in aortic endothelial cells in culture were assessed. Further, to identify circulating factors contributing to the serum effects on the bioactivity of endothelial cell mitoROS, metabolomics analyses alongside serum metabolite level normalization and human aortic endothelial cell serum exposure experiments were performed.¹

The findings showed that FMD_BA in postmenopausal women was lower compared with premenopausal women; however, FMD_BA was over 50% higher in late- versus normal-onset and positively related to age at menopause. Additionally, ΔFMD_{BA, MTQ} was over 50% lower in late- versus normal-onset postmenopausal 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, in a news release.²

Further, serum from normal-onset postmenopausal women—but not late-onset postmenopausal women—had caused a higher mitoROS bioactivity in human aortic endothelial cells compared with serum from premenopausal. Additionally, mitoROS bioactivity is shown to be largely related to FMD_BA as well as age at menopause.¹

“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,” senior author Matthew Rossman, an assistant research professor in the Department of Integrative Physiology, said in the news release.²

The investigators observed a total of 17 metabolites that significantly differed between the 2 different age groups: 15 were lipid-specific, whereas 8 were triglyceride-derived. TG(16:0) was considered to be the most strongly correlated with mitoROS bioactivity, and normalization of these concentrations within serum from premenopausal women and late-onset postmenopausal women to match serum levels in normal-onset postmenopausal women revoked any differences in mitoROS bioactivity in serum-treated human aortic endothelial cells.¹

The authors note that exploring how early-onset menopause might affect heart health and whether nutritional supplements—specifically those aimed at neutralizing free radicals within blood vessels—might reduce heart disease risk in women, particularly those considered to be higher risk. Additionally, future research can also determine if mitochondrial function or certain lipids circulating in the blood might play a role.²

“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 in the news release.²

REFERENCES

1. Darvish S, Murray KO, Ludwig KR, et al. Preservation of Vascular Endothelial Function in Late-Onset Postmenopausal Women. Circ Res. 2025.doi:10.1161/circresaha.124.325639

2. University of Colorado at Boulder. Later-onset menopause linked to healthier blood vessels, lower heart disease risk. News release. February 4, 2025. Accessed February 13, 2025. https://www.eurekalert.org/news-releases/1072647