Premature Menopause: A Warning Signal for CVD Risk

JoAnn E. Manson, MD, DrPH


December 23, 2019

This transcript has been edited for clarity.

Hello. I am Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts. I'd like to talk with you about a recent report from the UK Biobank that was posted in JAMA. The study examined the association between premature menopause (before age 40) and the risk for cardiovascular disease (CVD). This study included more than 144,000 women, and they looked at a broad composite endpoint of CVD, including coronary heart disease, stroke, heart failure, venous thromboembolism, and other vascular endpoints.

The study also looked separately at premature natural menopause and premature surgical menopause due to bilateral oophorectomy. They found that the hazard ratio for the composite endpoint in premature natural menopause was 1.36, and for premature surgical menopause, the hazard ratio was 1.87. The risk for individual vascular endpoints tended to increase as well. They also saw that cardiovascular risk factors such as hypertension, high cholesterol, and diabetes were all generally increased in the women with premature menopause.

They looked at age at menopause with a little more granularity and saw overall that there was a gradient, such that the women with the earliest age at menopause tended to have the highest risk for CVD. The excess risk became smaller as the age of menopause approached 50 years.

The investigators evaluated hormone therapy and estrogen therapy in a limited way, but other studies have suggested that among women with premature menopause, taking hormone therapy can offset some of the coronary risk as well as risks to bone health. Some organizations, such as the North American Menopause Society and the American College of Obstetricians and Gynecologists do endorse the use of hormone therapy for women with premature menopause, at least until the average age of menopause (50-51 years) among women without contraindications to hormone therapy.

The JAMA study suggests that premature menopause is a marker for cardiovascular risk, but the exact mechanism for this increased risk is not known. It may be due to early loss of estrogen. There is some evidence that cardiovascular risk factors may actually lead to an earlier age at menopause due to effects on the vascular system, such as decreased blood supply to the ovaries. It does appear that the relationship is bidirectional.

The finding from this study and many others, that premature and early menopause are markers for increased cardiovascular risk, suggests that it's important to target these high-risk women for primordial prevention. Excess risk can be minimized through lifestyle modification, control of blood pressure and lipids, and other treatments.

Thank you for your attention. This is JoAnn Manson.

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