Mifepristone for preoperative treatment of uterine leiomyoma

AIM: To explore the clinical impact and its molecular regulation on uterine leiomyomas in preoperative treatment with mifepristone, a progesterone receptor modulator (PRM). BACKGROUND: Uterine leiomyomas are highly prevalent in fertile women, increasing with age up to 35-50 % in a population approaching the age of 50. These most often benign tumors, frequently cause menorrhagia, and may interfere with fertility and the outcome of pregnancy. Progesterone and estrogen have a role in leiomyoma growth regulation, as well as in endometrial and breast cell proliferation and the development of endometrial and breast cancer. The objective of the current project was to study the effect of mifepristone on leiomyoma growth, as well as on cell proliferation in human endometrial and breast tissue in premenopausal women. METHODS: Thirty premenopausal women scheduled for surgical treatment due to uterine leiomyoma were randomized to either 50 mg mifepristone or non active treatment every other day, for 12 weeks before surgical intervention. Uterine and leiomyoma blood flow and leiomyoma volume were measured once a month until surgery. Endometrial biopsies were obtained and analyzed before and at end of treatment. Breast biopsies were assessed at baseline and at the end of the study for the expression of Ki-67 by immunocytochemical analysis in order to evaluate mammary epithelial cell proliferation. On surgery biopsies were collected from the periphery of the dominant leiomyoma. In order to investigate the gene expression leading to volume change in myoma, microarray analysis followed by Real time PCR analysis was performed. The degree of apoptosis was studied by TUNEL. Functional studies using primary cell cultures from fresh and untreated leiomyoma biopsies were performed to investigate the antiglucocorticoid response of mifepristone in the Integrin pathway. RESULTS: There was a significant difference in percentual volume regression of the dominant leiomyoma between the treatment groups (p=0.014). The controls (N=15) had a percentual n.s. increase in volume of mean (± 95% Confidence interval), +8% (-10%, +26%) over time. The mifepristone group (N=12) had a significant volume regression of -27% (-47%, -8%), p=0.028 within the mifepristone group and between the treatment groups at the end of study (p=0.014). Mifepristone treatment significantly reduced the number of bleeding days (p