Treatment-Induced Menopause Hikes CVD Risk: What to Know

This transcript has been edited for clarity.Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Mass General Brigham. I'd like to talk with you about a recent report on iatrogenic menopause (surgical bilateral oophorectomy or menopause medically induced by chemotherapy or radiation), age at menopause, and risk for cardiovascular morbidity and mortality, just published in JAMA Network Open.Although iatrogenic menopause is common and associated with an abrupt decline in ovarian hormones, its long-term cardiovascular and other health consequences are poorly studied, especially by age at the time of menopause. This report is a systematic review and meta-analysis, and one of the largest and most comprehensive ever done. It includes 36 studies, most of which are observational but two are randomized trials, and more than 2.6 million women. The report compared women with iatrogenic menopause before natural menopause age to naturally menopausal and age-matched controls. This study found that iatrogenic menopause was associated with higher risk for the primary endpoint of composite cardiovascular events, which included coronary heart disease, stroke, and all-cause mortality. But it was particularly the women with iatrogenic menopause before age 45 who experienced increased cardiovascular disease risk and excess mortality. Over a median follow-up of 16 years, iatrogenic menopause was associated with a statistically significant 25% higher risk for total cardiovascular events, 48% higher risk for coronary heart disease, 22% higher risk for stroke, and an 8% higher risk for all-cause mortality compared to women who were age-matched controls and had natural menopause.Among women with iatrogenic menopause before age 45, these risks were even greater, as all-cause mortality was increased by 15% and cardiovascular mortality significantly increased by 20%.Although statistical power was limited to look at whether menopausal estrogen therapy mitigated risk, the Women's Health Initiative randomized trial showed that randomization to estrogen therapy was associated with a 32% reduction in long-term all-cause mortality among the younger women with hysterectomy and bilateral oophorectomy, compared to randomization to placebo. So in conclusion, this meta-analysis provides further evidence that iatrogenic menopause is associated with elevated cardiovascular morbidity and excess mortality, especially for women below age 45 at time of menopause. These findings have utility to inform counseling and long-term monitoring and follow-up of women with iatrogenic menopause, and they also highlight the continuing need for more research on the role of age, type of menopause, and effects of estrogen therapy and other treatments in improving individualized counseling of this patient population.Thank you so much for your attention. This is JoAnn Manson.