Give Your Patients’ Heart a Break

It’s no secret among the medical community that cardiovascular disease is the number one killer of women.  

It’s incidence peaks roughly ten years later than men and can prove more fatal. In fact, more women die or experience complications like stroke and heart failure within 5 years of a myocardial infarction than their male counterparts.  

What might be putting women at greater cardiovascular risk during midlife and beyond? Many believe it’s menopause.  

Menopause sets cardiometabolic shifts in motion. When estradiol (E2) levels drop, a hormonal imbalance can occur, causing the body to distribute fat differently. The consequences are visible; muscle mass begins to deteriorate, and fat may accumulate around the midsection. In some cases, fat can even begin accumulating around the heart, known as pericardial fat. A heavy heart is never good.  

The menopause transition (MT) can create the perfect storm for metabolic syndrome, a condition prime for increased cardiovascular consequences, such as insulin resistance and lipid dysregulation. 

The timing of menopause’s onset has its own implications for cardiovascular health. The younger women are when their post-menopausal awakening begins (and ovarian function comes to an end), the higher the likelihood for future heart complications. An evaluation of 15 observational studies revealed an incredible result: for every year younger menopause starts, women experience a 3% increased risk of CVD incidents.  

Medical professionals recognize that the cardiometabolic shifts occurring during the MT aren’t solely connected to losses in estradiol. But disregarding E2’s role in heart health certainly isn’t serving women. During reproductive years, female metabolic homeostasis has estradiol to thank. Later in life, estradiol is no less important but far less prevalent.  

Estradiol appears to have a cardioprotective effect. It helps to regulate the mitochondrial energy production the heart desperately needs to oxygenate the body while simultaneously affecting numerous pathways directly connected to the cardiovascular system. Estradiol may be intimately involved in limiting oxidative stress, inflammation, and arterial endothelial dysfunction while promoting cardiac extracellular matrix stability. These factors are all known to impact the development of heart failure.  

In an editorial, Dr. Felice L. Gersh shares: “The pervasive concept that the primary ovarian hormone, estradiol, transforms from being beneficial to becoming a harmful force as a woman transitions from the reproductive years into menopause has never rung scientifically true, particularly when one understands the numerous CV mechanisms it oversees.” 

A recent review of post-menopausal data further demonstrates that timing can, in fact, be everything. Patients under the age of 60 who start hormone therapy within the first 10 years of menopause appear to have better cardiovascular outcomes than originally thought. Many clinical factors matter when identifying appropriate therapy. One patient’s journey is unlike the next. What remains true is the heart wants what it wants, and some hearts want hormones.  

References

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2. Gersh FL. Benefits of estrogen in cardiovascular diseases. Prog Cardiovasc Dis. 2020 May-Jun;63(3):392. doi: 10.1016/j.pcad.2020.03.008. Epub 2020 Mar 21. PMID: 32209375.
3. Hodis HN, Mack WJ. Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing. Cancer J. 2022 May-Jun 01;28(3):208-223. doi: 10.1097/PPO.0000000000000591. PMID: 35594469; PMCID: PMC9178928.
4. Mauvais-Jarvis F, Lindsey SH. Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations. J Clin Invest. 2024 Sep 3;134(17):e180073. doi: 10.1172/JCI180073. PMID: 39225098; PMCID: PMC11364390.
5. Oliver-Williams C, Glisic M, Shahzad S, Brown E, Pellegrino Baena C, Chadni M, Chowdhury R, Franco OH, Muka T. The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic review. Hum Reprod Update. 2019 Mar 1;25(2):257-271. doi: 10.1093/humupd/dmy039. PMID: 30508190.
6. Sabbatini AR, Kararigas G. Menopause-Related Estrogen Decrease and the Pathogenesis of HFpEF: JACC Review Topic of the Week. J Am Coll Cardiol. 2020 Mar 10;75(9):1074-1082. doi: 10.1016/j.jacc.2019.12.049. PMID: 32138968.
7. Uddenberg ER, Safwan N, Saadedine M, Hurtado MD, Faubion SS, Shufelt CL. Menopause transition and cardiovascular disease risk. Maturitas. 2024 Jul;185:107974. doi: 10.1016/j.maturitas.2024.107974. Epub 2024 Mar 22. PMID: 38555760.