From a mechanistic point of view, it is known that Metformin increases HDL, decreases LDL, increases insulin sensitivity, and decreases inflammation. Therefore, it is unsurprising that Metformin reduces atherosclerosis and, thus, heart disease. Large-scale retrospective studies have also shown that individuals with PCOS tend to have their blood work show better, more desirable sugars and lipid profiles if they take Metformin than if they don’t.

How PCOS Affects Atherosclerosis

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder common in individuals of reproductive age, characterized by irregular periods, high androgen levels, and often polycystic ovaries. PCOS not only impacts reproductive health but also significantly raises the risk of atherosclerosis, or plaque buildup in arteries, due to several interconnected factors.

Firstly, insulin resistance is prevalent in PCOS, leading to high insulin levels that worsen lipid profiles (elevated LDL, low HDL) and contribute to blood vessel damage. This insulin imbalance also triggers inflammation, harming artery walls and accelerating plaque formation.

Additionally, PCOS is often associated with obesity, particularly abdominal obesity, which further increases the risk for metabolic syndrome—a key driver of cardiovascular disease.

Elevated androgens in PCOS can independently impact cholesterol levels, blood pressure, and blood vessel health, all of which elevate atherosclerosis risk. Lastly, hypertension commonly co-occurs with PCOS, adding to the cardiovascular strain.

What Is Atherosclerosis, and Why Is It a Problem

One of the primary functions of blood is to carry oxygen around the body so that it may deliver oxygen to cells, a mandatory element to produce energy for cell survival. Atherosclerosis significantly hinders cell survival because it makes it more difficult for cells to get enough oxygen.

The most straightforward definition of atherosclerosis is the clogging of the arteries due to an inflammatory process. Atherosclerosis is a pathophysiologic process that affects everyone, starting in utero before they’re born and continuing until the individual passes away. The only question is the rate at which the process occurs. The atherosclerosis rate will eventually become clinically relevant if it is significant enough.

The equation below explains that if atherosclerosis makes the width of your arteries in half, there will be 16 times more resistance to flow; therefore, preventing atherosclerosis as much as possible is paramount.

Every individual has some level of atherosclerosis in their blood vessels even before being born, and the only important question is whether the rate at which the disease process occurs is relevant to a typical human lifespan.

Key Risk Factors Include Those That Promote the Rate of Atherosclerosis

• High LDL Cholesterol: Promotes plaque formation.
• Hypertension: Damages arterial walls, facilitating plaque buildup.
• Diabetes: High blood sugar levels contribute to arterial damage.
• Smoking and Obesity: Accelerate plaque accumulation.
• Sedentary Lifestyle: Reduces cardiovascular resilience.

Q = (π * ΔP * r^4) / (8 * η * L)

Where:

● Q is the volumetric flow rate of blood in the vessel

● ΔP is the pressure difference between the ends of the vessel

● r is the radius of the vessel

● η (eta) is the dynamic viscosity of the blood

● L is the length of the vessel

As one can see, the volume of flow is dependent on the radius to the 4th power; thus, even small decreases in the lumen diameter have significant implications.

Introductory Terms Such as CIMT and FMD

With respect to the article in question, two crucial parameters have to be defined.

CIMT (Carotid Intima-Media Thickness)

Definition: CIMT measures the thickness of the inner two layers (intima and media) of the carotid artery wall, typically assessed using ultrasound. It’s a non-invasive imaging marker of atherosclerosis. A larger CIMT means more atherosclerosis.

FMD (Flow-Mediated Dilation)

Definition: FMD measures the ability of blood vessels to dilate in response to increased blood flow. It is typically assessed in the brachial artery and reflects endothelial function, specifically nitric oxide (NO) availability, which is crucial for vascular health. A larger FMD is desirable.

Overall Significance

When a meta-analysis was performed, which is essentially a study of various studies designed to increase the statistical power of the conclusions, it was shown that there was a statistically meaningful decrease in CIMT and increase in FMD, both of which are desired results.

Reduction in CIMT

After taking Metformin, patients saw an average decrease of 0.11 millimeters in their CIMT.

Why This Matters: While 0.11 millimeters might seem tiny, even small reductions in CIMT are significant. Studies have shown that a 0.1 mm decrease in CIMT can correspond to a 10–15% reduction in the risk of cardiovascular events like heart attacks and strokes. So, Metformin’s effect could meaningfully lower your cardiovascular risk.

Improvement in FMD

The patients experienced an average increase of 3.25% in FMD after Metformin treatment.

Why This Matters: An increase in FMD indicates better endothelial function—the ability of your blood vessels to dilate properly. Improved FMD means your arteries are more responsive and healthier, which can reduce the risk of hypertension and other cardiovascular issues.

Clinical Significance and Key Takeaway

1)Unfortunately, it is still all too common for physicians to treat PCOS with only anti-contraceptives and anti-androgenic medications such as spironolactone. The larger the amount of evidence using different approaches increases the acceptance of the conclusion that Metformin should be almost always added to PCOS. If a physician denies a patient Metformin, there should be a solid rationale behind that decision. Now ultrasound evidence further cements the causal proof that metformin ameliorates atherosclerosis. 

2) It is likely that metformin would have similar effects on the health of non-PCOS patients, with abundant evidence to support this claim. The article chose to study PCOS patients because it is already established that metformin is one of the first-line medications for this condition, and the ultrasound differences would presumably be greater in magnitude per unit of time as PCOS is a factor for atherosclerosis. 

Disclaimer: This article is for informational purposes only and does not substitute professional medical advice. Always consult a qualified healthcare provider for guidance tailored to your health situation.

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