Nickan Research Institute Immunopathologia Persa 2423-8015 12 2 2026 07 01 From hyperandrogenism to tumorigenesis; a mechanistic perspective on cancer development in PCOS-affected women e44029 e44029 10.34172/ipp.2026.44029 EN Zahed Karimi https://orcid.org/0000-0002-2304-6779 Sara Abutalebi Nasrabad https://orcid.org/0009-0006-1445-761X Reza Farzaneh https://orcid.org/0009-0001-9074-2918 Seyed Amir Banikarim https://orcid.org/0009-0006-0785-9020 Farkhondeh Sameipoor https://orcid.org/0009-0002-5335-8260 Faezeh Khajeh https://orcid.org/0000-0002-7525-2216 Faezeh Nesaei https://orcid.org/0009-0004-4495-0398 Roya Raeisi Jaski https://orcid.org/0009-0002-6566-8493 Maryam Samadi https://orcid.org/0009-0002-1774-2425 Naeem Nikpour https://orcid.org/0000-0002-4265-5430 Journal Article 10.34172/ipp.2026.44029 2026 02 01 2026 03 18 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.