Polycystic ovary syndrome and cardiovascular risk in women: an underestimated link

PCOS is an endocrine disorder, meaning it’s linked to imbalances in hormone production and regulation, affecting up to 18% of women of reproductive age.

It is a complex condition, first described in 1935 by American physicians Irving F. Stein and Michael L. Leventhal, who identified an association between amenorrhea, signs of hyperandrogenism, and enlarged ovaries with multiple cysts. Since then, it has also been known as Stein-Leventhal syndrome.

Key features include:

• Presence of multiple ovarian cysts
• Endocrine alterations: irregular menstrual cycles, hyperandrogenism, obesity
• Metabolic changes: insulin resistance with resulting hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, and lipid profile abnormalities
• Psychological issues: increased anxiety, depression, and reduced quality of life

The exact causes of PCOS remain unclear, and the underlying pathophysiological mechanisms are complex and multifactorial. PCOS is believed to originate from a hormonal imbalance, mainly involving:

• Excess production of androgens (male hormones also present in women)
• Elevated insulin levels (the hormone that regulates blood sugar)

These two hormones disrupt normal ovarian function.

This imbalance may be influenced by:

• Genetic factors: PCOS often runs in families, suggesting hereditary predisposition
• Environmental factors: such as lifestyle and diet
• Metabolic factors: especially obesity and insulin resistance, which exacerbate hormonal imbalances
• Neuroendocrine factors: potential dysfunctions at the level of the hypothalamus or pituitary gland, which regulate ovarian activity

All these elements contribute to hormonal and metabolic dysfunctions that hinder ovulation, promote ovarian cyst formation, and affect multiple systems, including the cardiovascular system.

The metabolic abnormalities typical of PCOS, such as insulin resistance, hyperinsulinemia, glucose intolerance, type 2 diabetes, and dyslipidemia, are often accompanied by overweight or obesity. These conditions create a state of oxidative stress, where cells produce more harmful molecules (oxidants) than they can neutralize through natural defense systems (antioxidants). This mild but chronic inflammatory state damages the endothelial cells lining blood vessels, impairing their function.

Over time, this leads to the formation of atherosclerotic plaques and stiffening of the arteries, known as subclinical atherosclerosis, which significantly increases the risk of cardiovascular diseases, even before any symptoms appear.

While scientific studies don’t always agree on the degree to which PCOS directly causes heart disease, it’s clear that these hormonal and metabolic changes significantly increase the risk of developing potentially fatal cardiovascular conditions.

“Recent research shows that even young women, with an average age of around 46 and without weight issues, may have a higher risk of conditions like coronary artery disease and heart attacks. This suggests that in addition to lifestyle factors, there may also be a genetic component that predisposes some women with PCOS to cardiovascular issues,” explains Dr. Castelvecchio.

Even without overt symptoms, PCOS can have a silent but significant impact on heart health. Early identification of cardiovascular risk signs allows for timely, personalized interventions, preventing long-term consequences.

“Since PCOS is typically diagnosed in women aged around 20–30 years, it’s crucial to assess cardiovascular risk throughout a woman’s life, especially during the 30s and 40s,” says Dr. Castelvecchio.

Menstrual irregularities, often the first sign of PCOS, should prompt healthcare professionals to consider cardiovascular risk screening and initiate preventive measures against long-term cardiometabolic complications.

Screening should include:

• Measurement of weight, height, waist circumference, and BMI, with regular monitoring for any changes
• Evaluation of cardiovascular risk factors (obesity, smoking, dyslipidemia, hypertension, insulin resistance, impaired glucose tolerance, physical inactivity) and estimation of overall risk using validated tools like SCORE2, a European clinical tool that estimates 10-year risk of fatal and non-fatal cardiovascular events (e.g., heart attack, stroke) based on age, sex, blood pressure, cholesterol, and smoking habits
• Regular blood pressure checks
• Carotid artery Doppler ultrasound: a non-invasive scan to assess carotid intima-media thickness (CIMT), an early marker of atherosclerosis
• Echocardiogram with color Doppler: to assess heart wall thickness, chamber size, and epicardial adipose tissue (EAT), a fat deposit around the heart that’s considered a major risk factor for coronary artery disease, heart failure, and atrial fibrillation
• Lifestyle and nutrition education based on the “Life’s Essential 8” framework from the American Heart Association, which includes:
  • Healthy diet
  • Regular physical activity
  • Quality sleep
  • Healthy weight management
  • Blood pressure control
  • Cholesterol management
  • Blood sugar regulation
  • Smoking cessation

Improving even one of these areas can significantly reduce long-term cardiovascular risk.

“The key to protecting heart health in women with PCOS is continuous and informed prevention. Only through an integrated, personalized approach can we reduce cardiovascular events and improve quality of life,” concludes Dr. Castelvecchio.