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It's known that women's hearts change after menopause, but a new study from the University of Guelph is the first to reveal the hidden changes that occur during perimenopause – the stage preceding that of menopause.
These small underestimated changes have potential implications for the protection of women's hearts by introducing earlier use of hormone replacement therapy.
"We found that the possibility of using the therapy probably started much earlier than expected."
Glen Pyle, lead author of the study
It has long been known that the risk of heart disease in young women is lower than that of men, but this risk increases significantly after the drop in estrogen levels in women at menopause. However, little was known about what happens to the heart during perimenopause – the years before menopause, when hormonal changes begin.
Using a single mouse model, this study, published in the journal Acta Physiologica, revealed that women's hearts undergo subtle changes during perimenopause, indicating that the organ is stressed at this early stage.
"The heart looks the same and its functioning does not change, but what underlies its function is altered," said the professor of biomedical sciences. "So, it's like a house that looks good but there's a leak in the foundation, the changes are hidden but they are there."
One of the reasons why the impact of perimenopause on a woman's heart has not yet been studied is that a mouse model that accurately mimics human menopause has not existed so far, he added.
"We could cause instant menopause in lab mice by removing their ovaries, but that does not allow to reconstruct the gradual change in menopause.We now have an animal laboratory model in which we can make sure that the ovaries of a mouse fail slowly over time to mimic the menopausal progressive transition in women. "
For this study, the mice underwent menopause for more than four months. Meanwhile, the hearts of the mice continued to function normally, but some aspects of their heart muscle have changed.
"What we saw were stress markers, some pro-inflammatory cytokines (stress-indicating proteins) were higher, while others were not," he said.
The team then examined the heart's reaction when estrogen-imparting drugs were offered during perimenopause. This was a new approach because most estrogen replacement treatments are usually offered to women after menopause.
"We wanted to test the hypothesis of the opportune moment: the idea that there is a window of opportunity to take estrogen in order to see if we could identify that window and determine how menopause affected the estrogen response, "said Pyle.
They found that the heart's response to estrogenic compounds varied during the perimenopausal period, again suggesting that molecular changes had occurred during this critical transition period.
"It tells us that we can not just put estrogen into a heart many years after menopause because you are now treating a fundamentally altered heart, and this study shows that these changes occur during the perimenopausal period," he said. Pyle.
"It also tells us that timing is important and that it is probably necessary to move the window to restore estrogen therapy much earlier and without waiting after menopause.
Although estrogen is known to protect the heart and keep it strong, many women and doctors are worried about hormone replacement therapy because of a large HRT study that was stopped 20 years ago, fearing to be linked to an increase in cardiac events and cancer.
"No basic research on perimenopause had been done before this study because they had no way of doing it.We went back to the drawing board with this study, to the lab to get those answers on "The menopause changes the heart, it's a fundamental question that we need to find an answer to, and we know now that there are minor but important changes."
The important message of this research, said Pyle, is that estrogen replacement therapy should not be abandoned, but that it can still be used to protect hearts.
"We want to continue this research in order to refine estrogen replacement therapy, to determine how it can be used wisely because there is so much evidence that it works."
Source:
University of Guelph
Journal reference:
Pyle, G. et al. (2019) Cardiac changes during the perimenopausal period in a mouse model of ovarian failure caused by a VCD. Acta Physiologica. doi.org/10.1111/apha.13290.
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