Cardiometabolic Risks in Women with Polycystic Ovarian Syndrome (PCOS): Understanding Treatment Options

Polycystic Ovarian Syndrome (PCOS) is a common hormonal disorder among women of reproductive age, marked by symptoms such hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. In addition to affecting reproductive health, PCOS can lead to significant long-term risks for cardiovascular and metabolic health, particularly in certain subtypes of the condition. This may result in early signs of cardiovascular issues, including endothelial dysfunction, increased arterial stiffness, and higher levels of coronary artery calcium. The connection between PCOS and clinical cardiovascular disease (CVD) is still under discussion, with some studies indicating a higher risk while others find no clear link. 

This review explores new management options, such as lifestyle changes, medications like metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), hormonal contraceptives, and bariatric surgery. Given the cardiometabolic risks linked to PCOS, a holistic approach that includes early intervention addressing both reproductive and metabolic health is essential.

Diet intervention:

Good nutrition is essential for managing PCOS and preventing complications. Women with PCOS often have high-calorie, low-fiber diets, worsening symptoms and increasing chronic disease risk. Effective dietary strategies include the Mediterranean diet, which improves ovarian health and metabolic function, and the ketogenic diet, which aids short-term weight loss and insulin sensitivity. Additionally, low-glycemic index diets can reduce inflammation and regulate appetite. A tailored dietary approach, combined with regular exercise, is key to achieving sustainable management of PCOS.

Metformin:

PCOS is linked to metabolic syndrome components like obesity, dyslipidemia, and insulin resistance, increasing the risk of type 2 diabetes, cardiovascular disease, and hormone-responsive cancers. High androgen levels in PCOS are influenced by hyperinsulinemia. Metformin, an insulin sensitizer, effectively promotes ovulation, reduces androgen levels, and improves menstrual regularity by lowering insulin resistance. It also has anti-inflammatory effects and enhances glucose uptake without causing hypoglycemia. Metformin improves BMI and waist circumference in women with PCOS and is recommended in recent guidelines for women with metabolic symptoms due to its beneficial effects on health metrics related to the condition.

Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs):

Obesity affects over 50% of individuals with PCOS, and insulin resistance impacts 50-80%. Weight loss can improve symptoms and restore ovulation, as seen in a study where a 10 kg loss led to ovulation in 90% of obese infertile women.

GLP-1RAs are effective for metabolic management in PCOS, enhancing insulin secretion and promoting weight loss. They significantly reduce body weight and free testosterone levels, and show better results in improving insulin sensitivity compared to metformin alone. Combined treatment with GLP-1RAs and metformin also enhances reproductive health and cardiovascular outcomes.

Oral Contraceptives:

Hormonal contraceptives, such as oral contraceptives, patches, and vaginal rings, are the primary treatments for menstrual irregularities and symptoms like hirsutism and acne in women with PCOS. They regulate hormone levels, prevent ovulation, and decrease androgen production. While metformin is less effective than COCPs in improving androgen and metabolic markers, combining COCPs with metformin can enhance reductions in fasting glucose and insulin levels. The benefits of these treatments are generally greater when used together, according to 2023 International Guidelines.

Myo-Inositol:

Inositols, particularly myoinositol (MI) and D-chiro-inositol, are B vitamins that help regulate insulin signaling and are linked to insulin resistance. Research indicates that MI can improve menstrual regularity, carbohydrate metabolism, and symptoms of hyperandrogenism. However, results on MI's cardiometabolic effects are mixed. Comparisons with metformin show similar benefits in insulin sensitivity and menstrual regularity, but recent guidelines indicate that while inositols may have potential, their efficacy for clinical outcomes lacks strong evidence for recommendations.

Bariatric Surgery:

PCOS management mainly targets symptoms, often using oral contraceptives to address issues like excess androgens and irregular bleeding. For obese women, weight loss is beneficial, but lifestyle changes may not suffice for those with a BMI over 35 kg/m². Bariatric surgery, including Vertical Sleeve Gastrectomy and Roux-en-Y gastric bypass, offers significant and lasting weight loss and improves metabolic health, menstrual regularity, and hyperandrogenism. Studies show these surgeries can greatly reduce PCOS symptoms within a year, making them an effective treatment option.

Source: Pililis S, Lampsas S, Kountouri A, Pliouta L, Korakas E, Livadas S, Thymis J, Peppa M, Kalantaridou S, Oikonomou E, Ikonomidis I, Lambadiari V. The Cardiometabolic Risk in Women with Polycystic Ovarian Syndrome (PCOS): From Pathophysiology to Diagnosis and Treatment. Medicina (Kaunas). 2024 Oct 10;60(10):1656. doi: 10.3390/medicina60101656. PMID: 39459443; PMCID: PMC11509436.