From the Guidelines
The pathophysiology of Polycystic Ovary Syndrome (PCOS) is a complex interplay of insulin resistance, hyperandrogenism, and abnormal gonadotropin secretion, with the most recent evidence suggesting that insulin resistance plays a crucial role in the development of PCOS, as stated in the 2020 study 1. The current understanding of PCOS pathophysiology is based on the interaction of altered hypothalamic–pituitary–ovarian function and concomitant hyperinsulinemia/insulin resistance with promotion of androgen excess, as described in the 2024 study 1. Key features of PCOS pathophysiology include:
- Insulin resistance, which affects 70-80% of women with PCOS, particularly those who are overweight, leading to compensatory hyperinsulinemia 1
- Hyperandrogenism, which is characterized by elevated levels of androgens, such as testosterone, and is a key feature of PCOS 1
- Abnormal gonadotropin secretion, which is marked by an increased luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio, further stimulating ovarian androgen production 1 These factors contribute to the development of multiple small antral follicles that fail to mature properly, leading to follicular arrest and preventing ovulation, as well as the characteristic polycystic ovarian morphology. Additionally, chronic low-grade inflammation and genetic factors, such as certain gene variants related to androgen synthesis, insulin action, and inflammation, may also play important roles in PCOS development, as suggested by the 2024 study 1. Overall, the pathophysiology of PCOS is multifactorial, involving a complex interplay of hormonal, metabolic, and genetic factors, which is supported by the most recent and highest quality evidence from the 2024 study 1.
From the Research
Pathophysiology of PCOS
The pathophysiology of Polycystic Ovary Syndrome (PCOS) is a complex and multifactorial process, involving a combination of genetic, environmental, and hormonal factors. The key features of PCOS include:
- Hyperandrogenism
- Oligo- or an-ovulation
- Polycystic ovaries
Hormonal Imbalance
The persistent hormonal imbalance in PCOS leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females 2. The hormonal imbalance is characterized by:
- Hyperandrogenism, which causes insulin resistance and hyperglycemia
- Insulin resistance, which leads to ROS formation, oxidative stress, and abdominal adiposity
- Elevated levels of androgens, which favors the development of insulin resistance, thus perpetuating the cycle of insulin resistance-hyperinsulinemia-hyperandrogenism 3
Genetic Factors
Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances in PCOS females 4. The genetic approach to elucidate the mechanism of pathogenesis of PCOS has identified several genes associated with the disease, including those involved in the steroidogenesis pathway 5. PCOS genetic inheritance is autosomal dominant, but the latest investigations revealed it as a multigene origin disease 4.
Metabolic Abnormalities
PCOS is associated with several metabolic abnormalities, including:
- Insulin resistance
- Hyperinsulinemia
- Dyslipidemia
- Obesity
- Cardiovascular disease
These metabolic abnormalities are linked to the hormonal imbalance and genetic factors, and contribute to the development of PCOS 2, 6.
Oxidative Stress and Inflammation
Oxidative stress and inflammation play a crucial role in the pathophysiology of PCOS. The elevation of advanced glycosylation end-products (AGEs) in the body, either produced endogenously or consumed from diet, exaggerates PCOS symptoms and is related to ovarian dysfunction 2. The chronic low-grade inflammation in PCOS involves alterations in the follicular microenvironment, which contributes to the development of infertility in PCOS patients 2.