Cardiovascular disease (CVD) is the leading cause of death in women and the risk dramatically increases with menopause. Although there are many factors involved in the development of CVD, the hormonal shifts experienced during the transition into menopause may play a significant part. Estrogen is one of the key transitional hormones during this changeover and its low levels during menopause are strongly associated with increasing cardiovascular risk.
Every year, 1 in 4 deaths are caused by heart disease. While some risk factors are out of our control — such as family history, genetics and ageing — most of the risk factors for developing cardiovascular disease are within our control, including lifestyle habits such as smoking cessation, physical activity, healthy food selection and how we cope with mental and emotional stressors.
Estrogen Research Through the Years
Estrogen’s cardioprotective properties haven’t always been well understood. Early analysis of the Women’s Health Initiative (WHI) incorrectly attributed the negative cardiovascular side effects of co-administered medroxyprogesterone acetate to Premarin. This sent the field of hormone replacement therapy into a serious identity crisis.
What we know now, after years of further analysis and from a great many follow-up studies to the WHI, is that estrogen replacement therapy actually decreases cardiovascular risk when prescribed early in menopause. Researchers proposed the “timing hypothesis” — suggesting that menopausal hormone replacement is cardioprotective if initiated in women who are perimenopausal or early postmenopausal, whereas starting estrogen replacement in late postmenopausal women (>10 years) showed either no benefit or detrimental effects on the cardiovascular system.
Data also suggested that transdermal delivery of estradiol lowered the risk of major coronary heart disease (CHD) compared to oral delivery.
How Estrogen Protects the Cardiovascular System
Blood Lipids and Vascular Tone
Known actions of estrogen include: raising high density lipoproteins (HDL); lowering cholesterol and low-density lipoproteins (LDL); dilating and relaxing blood vessels; and protecting endothelial function. Changes in blood lipid levels, vascular tone and the endothelial cells are major risk factors for developing cardiovascular disease.
Endothelial Dysfunction and Nitric Oxide
Vascular ageing has elements of endothelial dysfunction and atherosclerosis development and is a major risk factor for developing CVD. The menopause transition seems to accelerate vascular ageing, and estrogen decline contributes to this in several ways.
The term “endothelial dysfunction” describes defects in the production or bioavailability of endothelial-derived nitric oxide (NO) and the consequential damaging changes in vascular dilation or reactivity. Nitric oxide’s primary role in the cardiovascular system is to control vascular tone, dilate blood vessels, reduce blood pressure and inhibit platelet aggregation in arteries to prevent clotting and thrombotic events.
Estrogen has been shown to enhance NO production through oestrogen receptor (ER)α-mediated activation of nitric oxide synthase (eNOS) in endothelial cells. Extended times of lower estrogen can reduce ERα expression, causing functional impairment of ERα/eNOS signalling.
Endothelial function gradually declines in men over 40, but the decline in women begins at 50 years of age and accelerates after menopause as estrogen levels plummet. Studies using brachial artery flow-mediated dilation (FMD) showed that vasodilation was highest in premenopausal women, lower in perimenopausal women and lowest in postmenopausal women — with higher FSH and lower estradiol concentrations correlating with lower FMD measurements.
Antioxidant and Anti-Inflammatory Effects
Estrogen also displays antioxidant effects and protects against oxidative stress. With ageing and estrogen deficiency, the inflammatory marker tumour necrosis factor alpha (TNFα) is upregulated, activating adhesion molecules that attach to the walls of blood vessels, creating more inflammation and plaque formation. TNFα also scavenges NO, decreasing its bioavailability and setting up a cascade of events increasing inflammation. Estrogen replacement in menopause can stimulate NO release to help regulate inflammatory cytokines.
For women who want to understand their cardiovascular and hormonal risk profile together, our Complete Hormone & CardioMetabolic Test Kit measures key sex hormones alongside cardiometabolic markers — providing a comprehensive picture of how hormonal changes at menopause may be affecting cardiovascular risk.
Estrogen Replacement: Timing Is Key
The critical window for stemming cardiovascular or coronary heart disease has been shown to be the time when estrogen appears to begin its descent. Trying to ‘re-estrogenise’ women who are already in late menopause may not result in the expected changes seen in early perimenopausal women — perhaps because longstanding estrogen deficiency alters the epigenetic terrain to the extent that the body will no longer react as favourably to estrogen supplementation.
The importance of initiating estrogen therapy early in menopause for cardiovascular health cannot be overstated. Without estrogen’s role in modulating the vascular effects of nitric oxide and TNFα, and its influence on blood lipids, women are left at greater risk of a cardiovascular event and more likely to end up on a polypharmacy collection of statins, hypertension and anti-inflammatory drugs — all of which carry their own risk of adverse outcomes.
Testing Your Estrogen Levels
To find out if you are estrogen deficient, our Comprehensive Female Saliva Hormone Profile (LCMS) measures the free, bioavailable fraction of estradiol, progesterone, testosterone and DHEA using gold-standard LCMS analysis — the most clinically relevant method for identifying the hormonal imbalances associated with menopause and cardiovascular risk.
For a broader cardiometabolic assessment, our CardioMetabolic Test Kit measures lipid markers, insulin, HbA1c and inflammatory markers from a simple at-home blood spot collection — helping to identify the metabolic risk factors that accelerate cardiovascular disease in the context of hormonal change.
Learn more about hormonal imbalances during menopause and order your next test kit today.
Originally by Dr. Sherry LaBeck, ZRT Laboratory. Reproduced with permission. Last reviewed: May 2026.