October 08, 2019
2 min read

Premature, early menopause increase risk for nonfatal CVD events

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Women who had premature and early menopause had an increased risk for a nonfatal CVD event before age 60 years compared with those who had menopause from age 50 to 51 years, according to a pooled analysis published in The Lancet Public Health.

This increased risk was not present after age 70 years in women who had early menopause, according to the study.

“Identifying women with early menopause offers a window of opportunity for their doctors to work with them to monitor and actively manage cardiovascular disease risk factors,” Dongshan Zhu, PhD candidate at University of Queensland School of Public Health in Australia, said in a press release. “Early clinical diagnosis will help to improve overall cardiovascular health in their postmenopausal years.”

Menopause status

Researchers analyzed data from 301,438 women (mean age at last follow-up, 57 years; mean age at menopause, 50 years) from 15 observational studies performed between 1946 and 2013. Women were included in the study if they reported their age at natural menopause, natural menopause status and CVD status. Those who had oophorectomy or hysterectomy or reported use of oral contraceptives or menopausal hormone therapy were excluded.

Women were then categorized by age at menopause: premenopausal or perimenopausal, premature menopause (younger than 40 years), early menopause (40 to 44 years), relatively early menopause (45 to 49 years), reference category (50 to 51 years), relatively late menopause (52 to 54 years) and late menopause (55 years or older).

The primary endpoint was the occurrence of first nonfatal CVD, which was defined as a composite of stroke or incident CHD.

Nonfatal CVD events after menopause occurred in 4.3% of women. Of these events, 3.1% were CHD events and 1.4% were strokes.

CVD risk was higher in women with premature menopause (HR = 1.55; 95% CI, 1.38-1.73), early menopause (HR = 1.3; 95% CI, 1.22-1.39) or relatively early menopause (HR = 1.12; 95% CI, 1.07-1.18) compared with those who had menopause from age 50 to 51 years. Women who had menopause after age 51 years had a reduction in the risk for CVD (P for trend < .0001).

This association persisted in women who never smoked. The strongest association was seen before age 60 years in women with premature menopause (HR = 1.88; 95% CI, 1.62-2.2) and early menopause (HR = 1.4; 95% CI, 1.27-1.54). This risk diminished from age 60 to 69 years, and no significant link was seen at age 70 years or older.


“Endogenous estrogens have protective effects on the cardiovascular system,” Zhu and colleagues wrote. “Estrogen increases vasodilatation and inhibits the response of blood vessels to injury and the development of atherosclerosis. Early loss of estrogen might impair vascular function and increase the expression of inflammatory cytokines at younger ages, which might further damage the vascular function.”

Further research

An editorial was also published, in which Lizelle Bernhardt, RN, PhD student in the department of cardiovascular sciences at the University of Leicester in the United Kingdom, and Claire A. Lawson, PhD, research fellow at the University of Leicester, wrote: “Studies further elucidating the mechanisms that underpin the complex associations between sex and cardiovascular disease risk are essential to inform the redesign of primary and secondary prevention guidelines and make the necessary shift away from a one-size-fits-all approach to a more patient-centered approach to target the increasing global burden of cardiovascular disease.” – by Darlene Dobkowski

Disclosures: The authors of the study and the editorial report no relevant financial disclosures.