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Group van der Schouw

An early age of onset of menopause increases a women’s risk of cardiovascular disease. It’s long been thought that the drop in estrogen levels directly correlates with increased risk of heart disease, however, studies that give women extra estrogen are not effective in alleviating this risk. We’re using genome wide association studies to look at genetic variants to see whether these will give us more insight into the underlying molecular mechanisms between menopause and cardiovascular disease.  

Estrogen therapy for menopause does not reduce the risk of cardiovascular disease

We can observe and track a woman’s reproductive events -- menstruation, conception, childbirth and menopause. All these events are related to a woman’s cardiovascular risk. On average, women enter menopause at 50-51 years of age, and it’s known that for every year a woman enters menopause early, her risk of heart disease increases by 2%. During menopause, estrogen hormone levels drop by 80%; therefore, estrogen was considered a direct link to the risk of heart disease. Unfortunately, it appears that estrogen loss is not the only cause of the increased risk since supplemental estrogen has shown no effect in reducing the risk of heart disease.

Uncovering the relationship between menopause and heart disease

Despite decades of studies on hormone therapy, we’re still no closer to understanding the relationship between menopause and the increased risk of cardiovascular disease in women. Therefore, we’re using methods such as Mendelian randomization studies and genome-wide association studies, to identify genetic variants based on observations in large cohorts of patients. What’s interesting about this approach, is that rather than being hypothesis-driven (first asking a question, then finding an answer), these methods allow us to integrate hypothesis-free discovery into our research. So far, we’ve identified 54 genetic variants. Surprisingly, none of the variants are hormone-related. Instead, we see many variants that are involved in DNA repair. This suggests that we should start looking at other cellular and molecular pathways.

Are women born with clues of higher risk of heart disease?

When a baby girl is born, she has her full supply of oocytes, which we know determines the onset of menopause. We see potential links in early reproductive years between ovarian aging and heart disease. This indicates that there may be an underlying molecular predisposition to increased risk of heart disease very early on in development. 

As an epidemiologist, I believe we need to continously adjust to the our increasing capabilities. We now have the opportunity to take a more encompassing approach to our studies. Our computational analyses are becoming more complex, and as we learn how to handle them, it brings us another step closer to unraveling apsects of the pathways between menopause and heart disease. 

Researchers

Principal investigator

Reseachers

PhD students

  • Linda E.T. Vissers, MD
  • Marjolein C. Harbers, MSc
  • Renee M.G. Verdiesen, MSc
  • Sabine R. Zwakenberg, MSc
  • Veerle Dam, MSc
  • Sigrid Mueller-Schotte