Un-linking Menopause from Heart Disease – A New Paradigm?

The idea that heart disease mortality rises dramatically at menopause has been one of the truisms of medicine that spawned a generation of hormone use by women and led to the rise and subsequent fall of Prempro in the Women’s Health Initiative, the end-all-be-all study that failed to prove the truism. The truism is still so strongly believed that research to prove it right continues, using different hormone formulations and different cohorts of women, in the hopes that the hormonal fountain of youth was just misbranded and given to the wrong aged cohort.

Now comes a landmark study that suggests that what we’ve thought all along about heart disease and menopause may actually be wrong.

Dhananjay Vaidya and colleagues at Johns Hopkins and the University of Alabama have re-analyzed mortality data on men and women in the UK and US and concluded that, contrary to popular belief, heart disease rates and mortality do not increase dramatically with menopause, but rather rise more gradually as a function of age in both men and women.

“Our data show there is no big shift toward higher fatal heart attack rates after menopause,” said study leader Dhananjay Vaidya, an assistant professor of medicine at the Johns Hopkins University School of Medicine. “What we believe is going on is that the cells of the heart and arteries are aging like every other tissue in the body, and that is why we see more and more heart attacks every year as women age. Aging itself is an adequate explanation, and the arrival of menopause with its altered hormonal impact does not seem to play a role.”

Statistical mumbo-jumbo

(I am no statistician, so what follows is my own interpretation of what I read in the paper. )

The researchers  use of logarithmic instead of linear graphing of statistical data, and state that it is a better way to measure associations such as heart disease with age. What I think they are saying is that it is better to describe mortality at a given point in time as a proportion of previous mortality than to graph absolute mortality rates at different points in time.  They state that their way of looking at the data aligns more with heart disease being a function of aging and loss of repair mechanisms with time, as opposed to some dramatic external force changing the curve at a given time. By restricting the analysis to various ageing cohorts over time, they also can compensate somewhat for improvements in prevention(such as statins) that can affect heart disease rates in a younger populations compared to, say, their parents.

A Very Compelling Argument

I have to say after reading the paper that that Vaidya and colleagues make a very compelling argument for rethinking the old truisms that have had us looking to estrogen as the holy grail of heart disease prevention in women.

However compelling, the study does not change anything at the moment in my clinical practice, since I do not prescribe hormones for heart disease prevention. I will continue to offer HRT as one of several treatment options for women suffering from menopausal symptoms, so long as they understand its risks as well as benefits. (See my 10 Rules for Prescribing HRT)

The Breast Cancer Mortality Data is Even More Interesting

Even more interesting was the researchers’ finding that breast cancer mortality, in contrast to breast cancer incidence, decreases dramatically at menopause.

This would argue strongly against the routine use of hormone replacement in menopause. It also would argue that the bang for the buck in mammogram screening may be better spent on younger than older women, something that flies in the face of the recent USPSTF recommendations to back off on one-size fits all routine mammograms in younger women.

Wow.

This is really fascinating stuff. It really turns the so-called window hypothesis on its head. (The window hypothesis says that there is a small window of time around menopause in which to start HRT to get it’s cardiac benefits, and that starting it too late, as was done in the WHI, actually can be harmful.)

The study also  hammers the biggest nail yet into the coffin of HRT as the anti-aging cure for all women.

I can’t wait to hear this study discussed at the upcoming Menopause Society Meetings in Washington.  So glad I am going – this is sure to be one interesting meeting. Stay tuned…