Michael Honigberg, MD: Early Menopause - Cardiovascular Disease Risk

Cardiovascular disease affects men and women indiscriminately, as some female characteristics or likelihoods are greater drivers of some cardiovascular events. Premature menopause appears to be one of them.

In a recent interview with MD Magazine®, Michael Honigberg, MD, a research fellow in medicine at the Massachusetts General Hospital, shared new trial data conducted by himself and his team and presented at the American Heart Association (AHA) 2019 Scientific Sessions which showed that women to experience menopause prior to age 40 are at a greater risk of cardiovascular events, regardless of other risk factors.

Honigberg: The motivation for this study was recent guideline updates to the American College of Cardiology and American Heart Association guidelines for the management of cholesterol and primary cardiovascular prevention, which last year and this year elevated a history of premature menopause to be a so-called "risk enhancing factor," to better risk-stratify women for their risk of cardiovascular disease, and guide the provision of statin therapy.

That recommendation was based on not the most robust evidence base, and the guidelines picked an age cutoff of 40 to guide their risk refinement strategy.

We thought there were many unanswered questions about the history of premature menopause and how it influences a women's cardiovascular disease risk. So, we used the UK Biobank, which is a very large, population-based cohort study UK adult residents, and we studied 144,000 women who had already undergone menopause. We studied both premature natural or spontaneously occurring menopause, as well as premature surgical menopause—or menopause induced by surgical removal of the ovaries.

We followed women who had not yet established cardiovascular disease, prospectively for the development of new cardiovascular disease diagnoses. In addition, we followed these women for the development of risk factors for cardiovascular disease—specifically, hypertension, hyperlipidemia, and diabetes.

And we found that women with a history of premature natural and surgical menopause faced elevated risks of future cardiovascular disease, and that extended to diseases we already knew were associated with premature menopause, like coronary heart disease and stroke, but extended to many other diagnoses as well, such as heart failure, valvular heart disease, arrhythmia, and venous thromboembolic disease.

There was a suggestion that the risks might be higher after surgical, compared to natural, premature menopause. In addition, we found the risks continue to increase with progressively earlier age in menopause.

So, the guidelines endorse using an age cutoff of 40 to risk-stratify women. But we found the risks began to increase a little bit, even in women who had menopause just a little bit earlier than average, and then became quite extreme with very, very early age of menopause—before age 35 or even 30.

So, I think it gives us more of a nuanced and detailed understanding of exactly how menopausal history tracks with cardiovascular disease risk.

Separately, and I should just emphasize that all of those findings held after we adjusted for conventional cardiovascular disease risk factors. However, we found women with a history of premature menopause also developed new cardiovascular disease risk factors earlier.

That was seen across hypertension, hyperlipidemia, and type 2 diabetes.