Md Soriful Islam

Advances in uterine fibroid research: linking progesterone and the transforming growth factor-β signaling pathway

The Potential of Vitamin D and Epigallocatechin Gallate (EGCG) for the Treatment of Uterine Fibroids: Evidence From In Vitro to Clinical Studies

ABSTRACT Uterine fibroids are prevalent benign tumors of the female reproductive tract that cause significant morbidity. Accumulating evidence suggests an association between vitamin D deficiency and uterine fibroid prevalence. Vitamin D, synthesized through sunlight exposure and obtained from fatty fish and fortified foods, regulates key processes, such as cell proliferation and apoptosis. In vitro and in vivo studies have demonstrated the efficacy of vitamin D against uterine fibroids. Clinical evidence further supports its role in fibroid management, as evidenced by a decrease in fibroid incidence, volume, and growth rate. Similarly, EGCG, a major polyphenol in green tea, inhibits cell proliferation and fibrosis while inducing apoptosis. Both in vitro and in vivo studies reveal the potential of EGCG in fibroid treatment, with clinical trials corroborating these findings. Given their complementary mechanisms, a synergistic effect of combined vitamin D and EGCG treatment has been explored. Preliminary clinical evidence indicates promising results, including reduction in fibroid volume, improved surgical outcomes, and enhanced quality of life. This review synthesizes current knowledge of vitamin D and EGCG mechanisms of action, presents preclinical and clinical evidence, and discusses the emerging evidence for their combination therapy as a non‐invasive, cost‐effective treatment strategy for uterine fibroids.

Progesterone signaling in uterine fibroids: Molecular mechanisms and therapeutic opportunities

Progesterone (P4) is a vital female sex hormone involved in various physiological processes, including the maintenance of the endometrium, mammary gland development, and bone health. Beyond its reproductive roles, P4 is implicated in the pathogenesis of hormone-dependent conditions like uterine fibroids, the most common benign tumors in women, which can severely affect quality of life and fertility. Traditionally, estrogen was considered the primary driver of fibroid growth, but recent research highlights the significant role of P4 in fibroid growth. P4 interacts with progesterone receptors (PRs) and non-genomic membrane receptors (mPRs and PGRMCs) to activate signaling pathways that enhance tumor growth and survival. P4 promotes vascular changes that improve the blood supply to fibroids and modifies the extracellular matrix, a key component of fibroid structure. This understanding has led to the investigation of selective progesterone receptor modulators (SPRMs) as potential therapies for fibroids. Clinical trials have demonstrated the effectiveness of SPRMs like mifepristone, asoprisnil, and ulipristal acetate in reducing fibroid size and symptoms, though concerns about safety, particularly with long-term use, remain. Newer SPRMs, such as vilaprisan, show promise, but further research is necessary to assess the long-term safety and effectiveness. This review discusses the mechanisms by which progesterone contributes to fibroid growth and examines clinical effectiveness of SPRMs as potential treatments for uterine fibroids.