What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Premature or early menopause (n=921517). Intervention: Premature menopause (age 45 years. Primary outcome: Coronary heart disease (RR 1.52, 95% CI 1.22-1.91).

March 21, 2023Open Access

The risk of long-term cardiometabolic disease in women with premature or early menopause: A systematic review and meta-analysis

Key Result

Premature menopause significantly increased the risk of coronary heart disease (RR 1.52) and total cardiovascular events (RR 1.36) compared to menopause at age >45 years.

Study Design

Type

Meta-Analysis (n=921,517)

Structured PICO

Does premature or early menopause increase the risk of long-term cardiometabolic disease in postmenopausal women?

Population

921,517 postmenopausal women from 20 cohort studies, followed for 4 to 67 years, to evaluate the association between premature or early menopause and long-term cardiometabolic disease.

Exposure

Premature menopause (age <40 years) or early menopause (age 40-45 years)

Comparator

Menopause at age >45 years (majority 50-54 years)

Outcome

Type 2 diabetes, hypertension, hyperlipidemia, coronary heart disease, stroke, and total cardiovascular eventshard clinical

Premature and early menopause are associated with a significantly increased risk of long-term cardiometabolic diseases, including coronary heart disease and stroke, compared to menopause at age >45 years.

Main Result

Relative Risk: 1.52 (95% CI 1.22–1.91)

Limitations

Clinical heterogeneity due to different reference ages for normal menopause across included studies.
Outcome measures were affected by differences in reporting methods, including self-reports versus device diagnoses.
Most studies did not distinguish between natural and surgical menopause, preventing subgroup analysis by menopause pattern.
Inability to assess the confounding effect of menopausal hormone therapy (MHT) use.
Potential recall bias from the use of self-reported age of menopause.

Abstract

Background: Transition into menopause is associated with an increased risk of cardiovascular disease (CVD). However, it is unclear whether the association exists between premature menopause (defined as age at menopause 40 years) or early menopause (defined as age at menopause 40-45 years) and CVD or cardiovascular risk factors. The aim of this review was to comprehensively evaluate and meta-analyze the most reliable evidence about the relationship between menopausal age and the risk of long-term cardiometabolic disease. Methods: ) index. Results: 921,517 participants from 20 cohort studies published between 1998 and 2022 were considered. Compared to women with menopause at age >45 years, women with premature menopause (PM) or early menopause (EM) had a higher risks of type 2 diabetes (RR: 1.32, 95% CI: 1.08-1.62; RR: 1.11, 95% CI: 0.91-1.36, respectively), hyperlipidemia (RR: 1.21, 95% CI: 1.05-1.39; RR: 1.17, 95% CI: 1.02-1.33, respectively), coronary heart disease (RR: 1.52, 95% CI: 1.22-1.91; RR: 1.19, 95% CI: 1.07-1.32, respectively), stroke (RR: 1.27, 95% CI: 1.02-1.58; RR: 1.13, 95% CI: 0.97-1.32, respectively) and total cardiovascular event (RR: 1.36, 95% CI: 1.16-1.60; RR: 1.14, 95% CI: 0.97-1.35, respectively). No difference was found for hypertension in PM or EM women (RR: 0.98, 95% CI: 0.89-1.07; RR: 0.97, 95% CI: 0.91-1.04, respectively). Additionally, we also found that PM women, but not EM women, were linked with an increased risk of ischemic and hemorrhagic stroke. However, this is not in line with the conclusion that both PM and EM had a higher risk of total stroke. Conclusion: Women with PM or EM have a higher risk of developing long-term CVD, compared to women with menopause at age >45 years. Therefore, we recommend early lifestyle interventions (e.g., maintaining a healthy lifestyle) and medical treatments (e.g., timely initiation of menopausal hormone therapy) to decrease the risk of cardiometabolic disease in early or premature menopausal women. Systematic Review Registration: PROSPERO, identifier CRD42022378750.

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