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

## TL;DR

This review explores how growth factors beyond VEGF and TGF-β contribute to the development of uterine fibroids and highlights recent advances in understanding their role for better treatments.

## Contribution

A comprehensive analysis of growth factor pathways in uterine fibroids, extending beyond VEGF and TGF-β with updated findings from 2015 to 2025.

## Key findings

- Growth factors like VEGF, TGF-β, and PDGF play key roles in fibroid angiogenesis and fibrosis.
- ECM remodeling and signaling pathway interactions are critical in fibroid development.
- Recent advances suggest growth factors can be used to develop new biomarkers and treatment strategies.

## Abstract

Uterine fibroids, sometimes known as uterine leiomyomas, are characterized as a non-cancerous gynecological disorder that can develop in the wall of the uterus, mainly in women who are able to become pregnant. They cause heavy bleeding, anemia, pain, and sometimes fertility issues, which represent a significant adverse impact on women’s health. Certain natural substances in the body, known as growth factors, send out specific chemical messages, which can push fibroids to develop, supporting fibroid cell multiply; create new blood vessels; and produce extra tissues. The main function of the growth factor is to support tissue repair and healing the injuries; however, in the case of fibroids, they become overly active, leading to the excessive development and growth of fibroid tissue. This review highlights the importance of growth factors in uterine fibroid biology, analyzing and searching scientific findings from the last 10 years. It explains how scientists have learned how growth factors work together and their influence on the fibroid development and structure. Additionally, recent scientific advances, including biomarkers and treatment options, can be more effective and invasive.

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.