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Premature menopause shows significant link to cardiovascular disease

Premature menopause is significantly linked to eventual atherosclerotic cardiovascular disease (ASCVD), according to a research letter in JAMA Cardiology.

“There is growing evidence to support that women who experience premature menopause, defined as menopause prior to age 40, have a higher risk of future cardiovascular events,” said first author Priya Freaney, MD, an advanced cardiovascular research and imaging fellow focused on women’s heart health and disease at Northwestern University in Chicago.

The investigators used the recommended practice guidelines of the Pooled Cohort Equations (PCEs) to predict 10-year risk of ASCVD.

“This is done by entering in a patient’s risk factors, such as age, blood pressure, presence of diabetes and cholesterol numbers,” Freaney told Contemporary OB/GYNÒ. “The predicted risk percentage helps clinicians determine what strategies and therapies to use to prevent cardiovascular disease. In general, the higher the 10-year risk, the more aggressive we are at implementing preventive strategies.”

However, the tool currently does not include premature menopause in the risk calculation. “We wanted to see if adding premature menopause to the risk calculator improved the ability to predict risk,” Freaney said.

The authors pooled individual-level participant data from Black (n = 5,466) and White (n = 10,584) postmenopausal women, aged 40 to 79, from 7 U.S. population-based cohorts.

Black women were slightly older and had significantly higher rates of hypertension, obesity, and diabetes than White women.

Premature menopause was also more common among Black women than White women: 17.4% vs. 9.8%, respectively.

In addition, premature menopause was significantly linked to ASCVD, independent of traditional risk factors, with hazard ratios (HRs) of 1.24 (95% confidence interval [CI]: 1.03 to 1.49) and 1.28 (95% CI: 1.13 to 1.45) for Black and White women, respectively.

However, there was no incremental benefit in ASCVD risk predictions when premature menopause was added to the PCEs, with categorical net reclassification improvement (NRI) values of 0.0007 (P =.91) and 0.003 (P =.37) for Black and White women, respectively.

In sensitivity analyses, comparable findings in model performance were observed for women with only natural menopause, for women with only surgical menopause, and for women aged 40 to 54 years.

“Although our study confirmed that premature menopause is in fact associated with higher rates of cardiovascular disease in women, the risk prediction with this calculator was not meaningfully different when premature menopause was added in,” Freaney said.

Nonetheless, the study’s findings likely suggest that traditional risk factors like high blood pressure, diabetes, high cholesterol and obesity are the most important contributors to cardiovascular disease, according to Freaney, and notably that these risk factors may develop earlier and to a worse degree in women who experience premature menopause.

“It is crucial, therefore, for clinicians to ask women about their menopause history, inquiring what age did you experience menopause, so that we can identify women at higher risk and work together with them to manage risk factors to reduce the risk of ASCVD,” Freaney said. “Strategies include optimizing blood pressure, blood sugar, and cholesterol; and counseling on diet, exercise and weight management.”

Moreover, women who have had menopause prior to the age of 40 should proactively ask their physicians about their personalized cardiovascular risk, according to Freaney, and engage in a discussion about what they can do to help reduce their risk to prevent heart attacks and strokes.


Freaney reports no relevant financial disclosures.


Freaney PM, Ning H, Carnethon M, et al. Premature menopause and 10-year risk prediction of atherosclerotic cardiovascular disease. JAMA Cardiol. Published online September 15, 2021. doi:10.1001/jamacardio.2021