Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate

Abstract

Uterine fibroids are the most frequent benign tumours in women of child-bearing age. Their symptoms are diverse and the quality of life of the women affected can be significantly impaired. While treatment to date has been primarily by means of surgical intervention, selective progesterone receptor modulators (SPRMs) open up new medication-based treatment options. EMA's Pharmacovigilance Risk Assessment Committee (PRAC) has recently completed its review of ESMYA® (ulipristal acetate, 5 mg), following reports of serious liver injury, including liver failure leading to transplantation in postmarketing settings. We will provide some information on the PRAC's recommendations to minimize this risk. Nevertheless, the effectiveness and safety of the SPRM ulipristal acetate (UPA), both with regard to preoperative administration and with regard to an intermittent administration as long-term treatment for patients with symptomatic uterine fibroids, have been shown in several clinical studies (PEARL I–IV).

EC313-a tissue selective SPRM reduces the growth and proliferation of uterine fibroids in a human uterine fibroid tissue xenograft model

“…Recent FDA-approved SPRMs, UPA and asoprisnil (ASO) (Fig. 1B,C) were withdrawn from the market due to the endometrial changes 8,9 . Another approach is gonadotropin-releasing hormone (GnRH) agonists, upon binding GnRH-analogues to GnRH receptors, an initial increase in the release of gonadotropins is followed by to GnRH receptor downregulation leads to reduced levels of sex hormones 10 .…”

“…Adverse effects of GnRH agonist therapy involves the full range of menopausal symptoms including vasomotor symptoms and decreased bone mineral density 14 . The GnRH antagonists Elagolix was recently approved for endometriosis treatment and is expected to be submitted for market authorization for treatment of heavy menstrual bleeding associated with UFs 9,15 . Other antagonists such as relugolix and linzagolix are in development for the treatment of endometriosis and UFs.…”

Clinical and Histologic Features of Uterine Myoma in Reproductive-Age Women Under the Treatment by Selective Progesterone Receptor Modulators

“…УА из-за структурного сходства с прогестероном может взаимодействовать с его рецепторами, и, в зависимости от изменения конформации рецептора, в соответствующем связывающем домене возникают репрессирующие или активирующие эффекты. Какой из эффектов УА будет доминировать -агонистический или антагонистический -зависит от его структуры и изменения конформации рецептора прогестерона, а также от наличия дополнительных факторов в конкретном типе клеток и от физиологического контекста, например уровня других гормонов [4,8].…”

Virtual Inhibition Analysis of Bioactive Compound Brazilin (Caesalpinia sappan L.) Toward Progesterone Receptor or Lonaprisan in Breast Cancer Proliferation

“…SPRMs is the substance of synthetic steroids that have an agonist and/or antagonistic effect on PR. This compound has a structure similar to progesterone, so it can stick to PR [26]. Brazilin's structure is almost similar to progesterone (Figure 3) [27][28] therefore, it can bind to PR because both have amino acid residues ILE896 and PHE895.…”