# The estrogen-progestogen-oxidative stress network in uterine fibroids: mechanistic insights and therapeutic opportunities

## TL;DR

This paper explores how estrogen, progesterone, and oxidative stress interact to drive uterine fibroid growth and suggests new treatment strategies.

## Contribution

The paper introduces the estrogen-progesterone-oxidative stress network as a novel model for understanding uterine fibroid progression.

## Key findings

- Hormonal imbalance increases reactive oxygen species and oxidative stress in uterine fibroids.
- The E-P-OS network explains high recurrence rates after hormone therapy or surgery.
- Combining hormone and antioxidant treatments may offer better therapeutic outcomes.

## Abstract

Uterine fibroids are benign tumors with high incidence and recurrence rates that still pose significant treatment challenges. Traditionally, it has been believed that estrogen and progesterone primarily drive the development and progression of uterine fibroids. Recent studies have revealed that hormonal imbalance can affect reactive oxygen species production and trigger a significant oxidative stress (OS) state. The OS status in uterine fibroids can further amplify the pathological effects caused by hormonal imbalance. This suggests that estrogen, progesterone, and OS may interact to form an estrogen-progesterone-oxidative stress (E-P-OS) network, collectively promoting the progression of uterine fibroids. This network model provides a theoretical basis for the high recurrence rates following hormone monotherapy or surgery. Therefore, we reviewed the molecular mechanisms underlying hormone-OS interactions within the E-P-OS network and elucidated its pathological effects in promoting uterine fibroid progression. The integrated perspective lays the theoretical foundation for developing novel therapies that simultaneously block hormone signaling and counteract oxidative damage. Additionally, we summarized current clinical strategies for hormone therapy and antioxidant treatment, identified potential combination therapy approaches, and explored key challenges in their clinical translation. This aims to provide new directions and evidence for advancing the precision treatment of uterine fibroids.