From hyperandrogenism to tumorigenesis; a mechanistic perspective on cancer development in PCOS-affected women

Abstract

The mechanistic sequence from hyperandrogenism to tumorigenesis in women with polycystic ovary syndrome (PCOS) encompasses a constellation of structural and functional aberrations spanning the endocrine, metabolic, immunologic, and genetic domains. Chronic hyperandrogenism incites an interconnected cascade through chronic anovulation and unopposed estrogen action, insulin resistance with hyperinsulinemia, low-grade systemic inflammation, oxidative stress, and gut dysbiosis, each playing a synergistic role in promoting oncogenesis. It has been demonstrated that, this syndrome is most strongly associated with an increased risk of endometrial cancer, with a more modest and less consistent association with ovarian and breast cancers. Thyroid cancer risk may also be elevated, particularly in younger women. The underlying mechanisms involve hormonal imbalances, metabolic dysfunction, chronic inflammation, and genetic predisposition. Women with PCOS should be monitored for early signs of these cancers, and management should focus on mitigating risk factors such as obesity, insulin resistance, and chronic anovulation.