Bisphenol exposure and gynecological health: A narrative review of current evidence and knowledge gaps

The widespread use of plastic has led to exposure to chemicals like bisphenols (BPs), particularly bisphenol A (BPA), which are crucial in the production of polycarbonate plastics and epoxy resins. Recent studies have raised concerns about the effect of bisphenols as endocrine disruptors as the risk factor for hormone-dependent gynecological diseases. Taking into attention the mechanism of BPs' action, particularly their ability to bind to estrogen receptors and subsequently activate further estrogen pathways, it seems essential to understand their impact on different diseases. Moreover, it is not only the estrogen pathway, which is activated, but also signaling pathways, contributing to cell proliferation and potentially leading to carcinogenesis, particularly in tissues with hormonal dependencies. This review examines the mechanisms by which BPs interact with hormonal pathways and highlights their potential role in various hormone-related conditions, including benign gynecological diseases: endometriosis and polyendocrine metabolic ovarian syndrome (PMOS)/polycystic ovary syndrome (PCOS) and female gynecological cancers concerning breast, uterus and ovaries. The review also highlights the need to re-evaluate pre-analytical, analytical, and post-analytical standard operating procedures to reduce confounding factors in measuring BPs in clinical samples and to better model their potential roles as risk factors in disease etiology.