Premenopausal CVD may mean menopause at an early age

March 20, 2019

The timing of a woman's cardiovascular event may play a prominent role in her menopause onset.

Early menopause has long been correlated with cardiovascular disease (CVD) events including stroke and heart attack. A new study suggests the converse may also be true; women who have had premenopausal CVDs were twice as likely to go through menopause at an early age.  

“We found women who had a cardiovascular event before age 35 had twice the risk of being in menopause by the time they reached 45,” said Dongshan Zhu, MD, lead author of the study and a researcher at the School of Public Health, University of Queensland, Brisbane, Australia. “Women who had them after 40 were more likely to experience a ‘normal’ menopause at around 51.”

Reduced estrogen circulation during menopause can trigger vascular aging, and recent findings suggest menopausal hormone therapy (MHT) may not reduce CVD risk and may even increase it.  “This inconsistency led us to consider the converse model, i.e., that cardiovascular damage itself is a driving factor in the process of ovarian aging,” the report said. “This model is indirectly supported by two studies. In the Framingham Heart Study, Kok et al. found that premenopausal cardiovascular risk factors were associated with younger age at menopause. Another study reported that women who experienced early natural menopause were more often smokers, had diabetes, and had higher average body mass index (BMI). CVD risk factors are associated with women’s age at natural menopause and the question that follows is whether premenopausal CVD events might also be linked to reproductive aging and early age at natural menopause. To date, no study has examined this question directly.” 

The authors used information from nine studies in the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) to look at the association between premenopausal CVD events and age at natural menopause. Data collection in the studies was both retrospective and prospective, with CVD events ascertained by self-report and/or hospital diagnosis. 

The analysis represents data from 177,750 women who answered yes or no to questions about pre-or postmenopausal CVD events as well as giving their age at onset of an event and at natural menopause. The researchers made adjustments in the data from the self-reported surveys for confounding factors such as race/ethnicity, BMI, education, hypertension, smoking, and family history of CVD. 

According to the report, the researchers used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. 

Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Risk of menopause before age 45 was twofold higher in women who experienced a first CVD event before age 35 than in those with no history of a premenopausal CVD event (adjusted RRR [95% CI] 1.92 [1.17-3.14] for any CVD, 1.86 [1.01-3.43] for CHD and 2.17 [1.43-3.30] for stroke). For 47% of premenopausal CVD events reported by patients, no validation was available in hospital records.

According to Dr. Zhu, these findings should send a strong message to doctors of young women with heart disease. “These women should be alerted by their physicians for their future high possibility of having early menopause, because early menopause is associated with higher risk of death, Type 2 diabetes and osteoporosis,” he said, adding that because most of the women in the study were white, more research is needed to see whether the findings hold true for women of other races and ethnic groups.