Early Menopause May Shape Women’s Heart Risk Differently by Smoking and Diabetes

Women who experience menopause earlier than usual may face a higher risk of certain cardiovascular problems, but that risk does not look the same for everyone. Smoking and type 2 diabetes appear to complicate the picture, according to a new systematic review and meta-analysis involving more than 1.77 million postmenopausal women.

Published in Frontiers in Public Health, the study, titled 'Association between early menopause and adverse cardiovascular events in postmenopausal women: a systematic review and meta-analysis stratified by smoking status and type 2 diabetes mellitus,' examined whether early menopause is linked with heart failure, coronary heart disease, stroke and all-cause mortality when women are grouped according to smoking and type 2 diabetes status.

For the analysis, researchers defined early menopause as natural menopause occurring before age 45, a category that included premature menopause before age 40 as well as menopause between ages 40 and 45. They searched PubMed, Web of Science, Embase and the Cochrane Library for relevant research available through January 2026. Seven cohort studies met the final criteria, collectively covering more than 1.77 million women.

Early menopause may leave the cardiovascular system vulnerable for longer

Estrogen does more than regulate reproductive health; it supports blood-vessel function, helps maintain a healthier cholesterol profile, limits oxidative stress and inflammation, and contributes to normal heart metabolism and function. When menopause happens early, the body loses these protective effects sooner, potentially leaving the cardiovascular system exposed to age-related changes for a longer period.

The researchers found a particularly clear pattern among women who did not smoke. Early menopause was associated with a 23% higher risk of heart failure compared with menopause occurring later. It was also associated with a 26% higher risk of coronary heart disease among non-smokers. The analysis found no statistically significant association between early menopause and either heart failure or coronary heart disease in women who smoked. That does not mean smoking somehow protects women from the cardiovascular effects of early menopause.

Smoking is itself a powerful cardiovascular risk factor, and the authors suggest its harmful effects could be strong enough to obscure the additional contribution associated with menopausal timing. Smoking can also damage ovarian function and accelerate the depletion of ovarian follicles, meaning smoking may contribute both to earlier menopause and cardiovascular disease. The smoking analyses contained only two studies for each cardiovascular outcome and showed considerable differences between studies. The researchers noted that variations in smoking definitions, smoking exposure and study populations could have influenced the pooled results.

Type 2 diabetes changes the heart-risk picture

Diabetes produced another distinct pattern.

Among women with type 2 diabetes, early menopause was associated with a 29% higher risk of heart failure. Women without type 2 diabetes also showed a higher heart-failure risk of about 19%, although this result sat right at the threshold of statistical significance and had substantial variation between studies, making it a finding that needs cautious interpretation.

The relationship with stroke looked different. Among women without type 2 diabetes, early menopause was associated with an 11% higher risk of stroke, with highly consistent results across the two contributing studies. Among women with diabetes, the estimated increase was also 11%, but the confidence interval included no effect, so the result was not statistically significant.

The biological overlap between diabetes and estrogen loss could help explain the stronger heart-failure finding. Type 2 diabetes can damage blood vessels through chronic high blood sugar, inflammation and advanced glycation end-products. Diabetes-related kidney disease can also promote fluid and sodium retention, placing additional pressure on the heart. Early menopause removes estrogen's vascular protection sooner, while estrogen deficiency itself may worsen insulin resistance. Together, these processes could accelerate atherosclerosis and changes in heart structure.

The researchers also considered why early menopause was not significantly associated with stroke among women with diabetes. One possibility involves diabetes treatments such as SGLT2 inhibitors, which have been linked with a lower risk of atrial fibrillation, an important cause of stroke. The paper stresses that this explanation is speculative because medication use was not collected or analysed in the review.

The findings matter, but they are not the final word

Early menopause was not significantly associated with all-cause mortality in either diabetes group. Women with type 2 diabetes had an estimated hazard ratio of 1.20, while those without diabetes had an estimate of 1.18, but neither reached statistical significance. The researchers suggest that limited sample sizes and follow-up periods may have made mortality differences harder to detect.

All seven included cohort studies received at least seven points on the Newcastle-Ottawa Scale, placing them in the researchers' high-quality category. The review also searched four major scientific databases, followed a registered protocol and was designed to examine how major cardiovascular risk factors might influence the relationship between menopause timing and cardiovascular outcomes.

Only seven studies qualified, and several subgroup results were based on just two studies. There were not enough suitable data to carry out the planned analyses for obesity and hypertension. Definitions of early menopause also differed among the original studies, with age cut-offs ranging from younger than 40 to younger than 45.

The researchers could not formally test whether smoking or diabetes truly changed the effect of early menopause because analyses were performed separately within each subgroup rather than through direct interaction testing. The certainty of evidence was rated low across the outcomes, reflecting the observational nature of the evidence, possible residual confounding and limited stratified data.

The practical message is therefore more nuanced than saying early menopause automatically causes heart disease. Menopause before 45 may be a useful marker of cardiovascular vulnerability, particularly when considered alongside established factors such as smoking and type 2 diabetes.

For women who do not smoke, the review found associations with higher risks of heart failure and coronary heart disease, while women without diabetes also showed a higher stroke risk. Among women with diabetes, heart failure stood out as the clearest association. The lack of significant findings in some other groups should not be interpreted as proof that no relationship exists, especially given the small number of studies and wide confidence intervals.

The researchers describe these findings as exploratory rather than definitive. Larger studies with consistent definitions of early menopause, detailed smoking exposure, diabetes control, medication use and other cardiovascular risk factors will be needed to determine exactly how these factors interact. For now, the study adds weight to the idea that the age at which natural menopause occurs can be meaningful information when assessing a woman's long-term cardiovascular health rather than simply a reproductive milestone.