Vilaprisan

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.

Uterine leiomyomas (ULMs) are classified into those with and without MED12 mutations (MED12m(+) and MED12m(−), respectively). This study was undertaken to establish a culture system to evaluate the effect of female hormones on the growth of ULM cells in each ULM subtype.

ULM cells isolated from MED12m(+) or MED12m(−) tissues were cultured in a monolayer for 7 days with four hormone treatments: estrogen (E) and progesterone (P) (E + P), E only (E), P only (P), and medium only (CTRL). They were also cultured in a 3D spheroid culture system with the above four treatments and a fifth treatment: E + P + selective progesterone receptor modulator (E + P + SPRM). The hormonal effects were evaluated based on cell number, spheroid size, and histology.

In the monolayer cultures, female hormones did not cause the proliferation of ULM cells of either subtype. In the spheroid cultures, spheroid sizes for both subtypes were significantly larger with the E + P and P treatments than with the CTRL and E treatments and were comparable in the E and E + P + SPRM treatments. Histological staining showed that collagen fibers were present only in the spheroids of the P‐treated groups of MED12m(+).

We established a 3D spheroid culture system to evaluate the effects of female hormones on ULM cells.