From the Guidelines
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by insulin resistance, hyperandrogenism, and ovulatory dysfunction, with a prevalence of 8%–13% according to the Rotterdam criteria 1. The pathophysiology of PCOS involves multiple interconnected factors, including:
- Insulin resistance (IR), which plays a crucial role in many symptoms of PCOS, regardless of body mass index (BMI) 1
- Hyperinsulinemia, resulting from IR, contributes to hyperandrogenism through effects on the pituitary, liver, and ovaries 1
- Obesity, which exacerbates IR and worsens all symptoms of PCOS 1
- Hormonal imbalance, specifically elevated androgens produced by the ovaries and adrenal glands
- Dysregulation of the hypothalamic-pituitary-ovarian axis, with altered secretion of gonadotropins (LH and FSH) The physiological abnormalities in PCOS manifest as:
- Irregular periods
- Excess hair growth
- Acne
- Weight gain (particularly around the abdomen)
- Fertility problems
- Increased long-term risks for type 2 diabetes, cardiovascular disease, endometrial cancer, and mental health disorders like depression and anxiety 1. Lifestyle modification or weight loss is postulated to improve many symptoms of PCOS, highlighting the importance of addressing insulin resistance and hyperandrogenism in the management of the condition 1.
From the Research
Physiology of PCOS
The physiology of Polycystic Ovary Syndrome (PCOS) is complex and involves multiple factors. Key aspects include:
- Hyperandrogenism (HA) and ovulatory dysfunction, which are the primary characteristics of PCOS 2, 3
- Insulin resistance (IR) and compensatory hyperinsulinemia (HI), which are common in women with PCOS and contribute to the development of HA 2, 3
- Mitochondrial dysfunction, which is present in PCOS patients and is linked to both IR and HA 2
Pathophysiological Factors
Several pathophysiological factors are involved in PCOS, including:
- Elevated androgen levels, which cause substantial misery and infertility problems 3
- Insulin resistance, which is directly linked to the overexposure of androgen and increases the risk of heart diseases and endometrial cancer 3, 4
- Genetic origins, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation, and disturbed folliculogenesis 4
Treatment and Management
Treatment and management of PCOS involve:
- Metformin, which has been shown to decrease HI and consequently HA, restoring metabolic and hormonal disorders in PCOS patients 2, 5
- Lifestyle intervention, followed by the introduction of insulin sensitizers, including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT2) inhibitors 4
- Anti-androgens, such as spironolactone, which can be used in combination with metformin to induce a more marked reduction of clinical and biochemical hyperandrogenism 6
Predictors of Response to Treatment
Predictors of response to metformin therapy in PCOS patients include: