Beyond Hormones (part1): A Functional Blueprint for Cardiometabolic Health in Menopause

Menopause marks not just the end of reproductive capability but a profound cardiometabolic inflection point. While vasomotor symptoms (VMS) have long dominated the clinical conversation, emerging science demands a broader lens. More than 60 million U.S. women live with cardiovascular disease (CVD)—the leading cause of death among women. Yet fewer than half of cardiologists feel adequately prepared to assess cardiovascular risk in women [1]. This is more than a knowledge gap—it is a systemic failure in women’s preventive care.

The abrupt decline in estrogen during menopause affects far more than reproductive physiology. It disrupts lipid metabolism, impairs endothelial function, escalates vascular stiffness, heightens systemic inflammation, and drives insulin resistance and visceral adiposity [2–4]. Women who experience frequent or severe VMS face a 77% higher risk of developing CVD [5]. From a functional cardiology perspective, menopause is not a time for passive observation, it is a critical opportunity to detect and reverse early signs of cardiovascular aging.

ESTROGEN’S DECLINE AND THE CARDIOVASCULAR SYSTEM

The decline in estrogen during menopause initiates multiple adverse physiological shifts that significantly increase cardiovascular risk in women.

Lipid Metabolism: Estrogen has favorable effects on lipid profiles, promoting higher High Density Lipoproteins (HDL)  and lower Low Density Lipoprotein (LDL) levels. Post menopause, however, is characterized by increases in total cholesterol, LDL, triglycerides, and a decrease in HDL. This shift—partly due to loss of estrogen’s regulation of hepatic LDL receptors and its antioxidant properties—leads to elevated ApoB levels and a more atherogenic lipid environment. Estrogen therapy has been shown to reverse some of these changes, improving lipid parameters including reductions in LDL and Lp(a), and increases in HDL.

Vascular Function: Estrogen promotes endothelial health and vascular elasticity by enhancing nitric oxide availability. Its decline contributes to endothelial dysfunction and arterial stiffness, as evidenced by reduced carotid artery distensibility in postmenopausal women. These changes are linked to rising systolic blood pressure and a higher incidence of coronary artery calcium (CAC), independent of age—suggesting hormonal withdrawal alone can promote coronary calcification.

Inflammation: Estrogen also exerts anti-inflammatory effects by modulating cytokine production and reducing oxidative stress. With its loss, systemic inflammation increases, marked by elevated hs-CRP and other pro-inflammatory markers. Central adiposity, which commonly increases during menopause, further exacerbates this inflammatory state. Notably, elevated hs-CRP is a strong predictor of cardiovascular events in postmenopausal women, even when LDL is normal, underscoring the need for inflammation-specific risk assessment.

Glucose and Insulin Regulation: Estradiol plays a critical role in insulin sensitivity. Its decline contributes to increased visceral fat, insulin resistance, and higher HOMA-IR values, even in normoglycemic women. This metabolic shift leads to higher triglycerides, reduced HDL, and a rise in small dense LDL particles. These changes collectively amplify cardiometabolic risk and contribute to the emergence of metabolic syndrome. Midlife women are therefore at increased risk for type 2 diabetes and atherosclerosis, even in the absence of overt hyperglycemia.

Estrobolome and Estrogen Homeostasis:  The estrobolome regulates estrogen recycling via enterohepatic circulation. After hepatic conjugation and biliary excretion, estrogens can be reactivated in the gut by β-glucuronidase-producing bacteria, then reabsorbed systemically. In a healthy, balanced microbiome, this supports estrogen homeostasis. However, dysbiosis—characterized by loss of microbial diversity or overgrowth of β-glucuronidase-producing species—can disrupt estrogen levels, leading either to estrogen deficiency (due to excessive elimination) or estrogen dominance (due to excessive reactivation). These imbalances may exacerbate menopausal symptoms and contribute to increased cardiovascular risk.

Gut Microbiome, Inflammation, and Cardiovascular Risk: The gut microbiota also modulates systemic inflammation and cardiometabolic function. Certain microbial species metabolize dietary choline and carnitine into trimethylamine N-oxide (TMAO), a pro-atherogenic compound linked to a twofold increased risk of major adverse cardiovascular events. In parallel, gut barrier dysfunction ("leaky gut") enables translocation of lipopolysaccharides (LPS), which can trigger chronic low-grade inflammation and insulin resistance—key drivers of endothelial damage and plaque formation. Conversely, beneficial gut bacteria produce short-chain fatty acids (SCFAs) such as butyrate, which exert anti-inflammatory effects, enhance insulin sensitivity, and support vascular health. Notably, estradiol has been shown to promote gut microbial diversity, suggesting that estrogen withdrawal may diminish SCFA production and further accelerate metabolic dysfunction.

Hormones & Oral Health: Estrogen decline increases the risk of oral health disorders, including periodontal disease, dry mouth, and burning mouth syndrome. These changes also affect the oral mucosa and salivary composition, heightening susceptibility to infections and discomfort. Estrogen receptors in oral tissues explain the direct hormonal influence.

Both oral diseases (such as periodontal disease) and cardiovascular disease are influenced by inflammatory processes. Menopause is associated with increased inflammation, which can contribute to both oral and cardiovascular conditions. Periodontal disease, more prevalent post menopause, contributes to systemic inflammation and endothelial stress. Chronic gum inflammation increases CVD risk by up to 19% [21]. 

THE SHORTCOMINGS OF CONVENTIONAL RISK STRATIFICATION

Traditional cardiology remains anchored to risk factors counting cholesterol, blood pressure, diabetes, smoking. While helpful, this framework fails to capture the multisystem dysregulation at play in the menopausal transition. Functional cardiology instead addresses:

    • Endothelial dysfunction and glycocalyx degradation

    • Inflammation and oxidative stress

    • Sarcopenia and mitochondrial decline

    • Oral and gut-derived immune triggers

    • Estrogen-related changes in insulin sensitivity, appetite, and vascular tone

    • Subclinical atherosclerosis detectable only with advanced imaging

Critically, conventional risk calculators underestimate cardiovascular risk in women, especially during perimenopause and early post menopause [6]. Tools like coronary artery calcium (CAC) scoring, carotid intima-media thickness (CIMT), and EndoPAT testing provide early insight into vascular integrity and plaque burden. Advanced labs—ApoB, Lp(a), oxLDL, hsCRP, myeloperoxidase (MPO), and HOMA-IR—allow clinicians to move from population-based predictions to personalized prevention.

PART 2 of "Beyond Hormones" - (coming soon)

ABOUT THE AUTHOR

Dr. Hwaida Hannoush is an internist, noninvasive cardiologist and former NIH researcher, specializing in functional and integrative approaches to heart health. She is the founder of Precimed Clinic, where she empowers women to reverse heart disease by addressing root causes. With a strong foundation in both clinical practice and research, Dr. Hannoush bridges science with personalized care. (for more information, visit her website @ https://precimedclinic.com)