Introduction: Selective progesterone receptor modulators (SPRMs) have been reported to decrease cell proliferation within uterine fibroids, and reduce menstrual blood loss. The SPRM Ulipristal Acetate (UPA) has an anti-proliferative effect on fibroid tissue, yet its impact on endometrial cell proliferation is not well understood. The aim of this study was to quantify the effects of the SPRM UPA administration on endometrial cell proliferation within the human endometrium.
Methods: Endometrial biopsies were collected with ethical approval and informed consent from women with uterine fibroids treated with UPA (12/SS/0238). Control proliferative and secretory phase endometrium was sourced from tissue archives (10/S1402/59). Endometrial samples were categorized into three groups (n=6 per group): proliferative phase (PP), secretory phase (SP) and UPA-treated endometrium (UPA). Endometrial samples were immuno-stained with two cell proliferation markers, Ki67 and PH-H3. For each proliferation marker, the immuno-stained stromal and glandular cell proliferation indices (CPI), within each tissue group, were measured using an established stereology method. The CPIs from each tissue group were compared, for each cell type, with multiple t tests. Statistical significance was adjusted to P<0.0167.
Results and discussion: The results show a reduction in Ki67 stained stromal and glandular CPI in the UPA-treated samples compared to the PP samples (P=0.0238 and P=0.0022 respectively). The results also demonstrate a significant reduction in Ki67 stained stromal and glandular cell CPI in the SP samples when compared to the PP samples (P=0.0043 and P=0.0022 respectively). These observations are consistent with an anti-proliferative effect of UPA on the human endometrium, which may play a role in the reduction of menstrual blood loss experienced by women prescribed with the SPRM, UPA. (Funding: Medical Research Council (MRC) Centre grant (G1002033) and Tenovus Scotland.)
11 Jul 2016 - 11 Jul 2016