Early menopause tied to elevated CVD risk

Early menopause may be linked to an elevated risk of cardiovascular disease (CVD) before age 60 years, according to a recent analysis.

The authors assessed individual data from 15 observational studies in the InterLACE consortium* comprising 301,438 women (mean age 57 years, 64 percent postmenopausal at last follow-up, mean age at menopause 50.2 years) from Australia, Japan, US, UK, and Scandinavia. About 4 percent of these women had a first incident of non-fatal CVD (composite of coronary heart disease [CHD] or stroke) following natural menopause**, of whom 3.1 and 1.4 percent had CHD and stroke, respectively.

Compared with the control  group (menopause at age 50–51 years), early menopause was linked to a higher risk of non-fatal CVD events in women who experienced premature menopause (age <40 years; hazard ratio [HR], 1.55, 95 percent confidence interval [CI], 1.38–1.73), early menopause (age 40–44 years; HR, 1.30, 95 percent CI, 1.22–1.39), or relatively early menopause (age 45–49 years; HR, 1.12, 95 percent CI, 1.07–1.18; p<0.0001 for all). [Lancet Public Health 2019;doi:10.1016/S2468-2667(19)30155-0]

The results were consistent in separate analyses of CHD and stroke risk. Each 1 year decrease in age at menopause was associated with a 3 percent increased risk of CVD (p<0.0001).

The risk of a first non-fatal CVD incident was greatest before age 60 years among women with premature, early, or relatively early menopause (HR, 1.88; p<0.0001, HR, 1.40; p<0.0001, and HR, 1.17; p=0.0002, respectively) compared with the control group, with no significant association noted at age ≥70 years.

Conversely, CVD risk was reduced in women who experienced late menopause (age ≥55 years; HR, 0.88), or those who were pre- or perimenopausal at last follow-up (HR, 0.52; p<0.0001 for both).

“The doubling of CVD risk in women below the age of 60 years who have premature menopause is concerning and indicates an urgent need to raise awareness of CVD risk in younger women,” commented Lizelle Bernhardt and Dr Claire Lawson from the University of Leicester in Leicester, UK. [Lancet Public Health 2019;doi:10.1016/S2468-2667(19)30184-7]

Among women with premature menopause, the use of menopausal hormone therapy did not alter CHD risk (HR, 1.64 and 1.62 for users and non-users, respectively; p<0.0001 for both), though stroke risk was elevated in hormone users compared with non-users (HR, 2.06; p<0.0001 and HR, 1.45; p=0.0067). However, the lack of sufficient information on type and dose of menopausal hormone therapy could have affected the results, said the authors.

Oestrogen has a protective effect on the CV system, and early oestrogen loss, as would occur in early menopause, could have a negative impact on vascular function, said the authors. Elevated androgen levels, low levels of sex hormone-binding globulin, and genetics could also play a role, they said.

“Identifying women with early menopause offers a window of opportunity for their doctors to work with them to monitor and actively manage CVD risk factors,” said lead author Dongshan Zhu, a PhD student at the University of Queensland, Brisbane, Australia. “Early clinical diagnosis will help to improve overall CV health in their postmenopausal years.”

“[T]hese findings demonstrate the potential for including sex-based factors to improve current prognostic models for women,” said Bernhardt and Lawson. Given the Caucasian-majority population, further research is warranted to assess if this association differs by ethnicity, they said.

Additionally, steps should be taken to reduce the likelihood of early menopause as well as CVD. These include smoking cessation and maintaining healthy BMI levels, said the co-authors.