Mechanical Stiffness Influences the Response of Human Uterine Fibroid Cells to Hormonal Treatments.

Uterine fibroids (UFs), the most common gynecologic tumors in reproductive-age women, are characterized by the accumulation of extracellular matrix (ECM), which leads to increased stiffness. The stiffness can transfer mechanical signals from the ECM to the intracellular environment through a process called mechanotransduction, consequently altering the biological behavior of the cell. UFs are estrogen and progesterone-dependent, with hormonal fluctuations influencing their growth and development. Consequently, the emphasis in medical treatment development has been on options that target steroid hormones, including GnRH agonists/antagonists, aromatase inhibitors, and anti-progestins. However, there has been limited understanding of how mechanical stiffness influences the progression of UFs and their cells’ response to medical treatments. This work aimed to assess the impact of stiffness on UFs cell growth and on their responsiveness to hormone and anti-hormonal treatments. Our results showed that increased stiffness enhances proliferation and ECM accumulation in UF cells, and that the mechanical environment influences the response of these cells to both hormone and anti-hormone treatments. These findings offer valuable insights for understanding UF pathogenesis, racial disparity as well as improving UF treatment strategies, emphasizing the importance of considering the mechanical microenvironment in clinical approaches. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43032-025-02016-0.