Beyond VEGF and TGF-β: A Comprehensive Review of Growth Factor Pathways in the Pathophysiology of Uterine Leiomyomas

Uterine leiomyomas or fibroids, are non-cancerous smooth muscle proliferations of the uterus, occurring mostly in women of reproductive age. Their pathogenesis involves complex growth factor interactions that regulate cellular proliferation, extracellular matrix (ECM) remodeling, and angiogenesis in myometrium. Women affected by fibroids often have a range of consequences such as infertility, endometriosis, and dysmenorrhea. Several growth factors such as vascular endothelial growth factor (VEGF), transforming growth factor (TGF-β), and platelet-derived growth factors (PDGF) have long been described as key regulators of angiogenic and fibrotic activities in fibroid tissue. Moreover, we summarized updated information between 2015 and 2025 following strictly inclusion/exclusion criteria and key research areas, including growth factors and its isoform-interaction, their roles within key signaling pathways, and the contribution of ECM deposition in uterine fibroids development and growth. Implementing growth factors in the clinical research field can develop new biomarkers and treatment options, focusing on effective and advanced management of uterine fibroids.