Effects of the Selective Progesterone Receptor Modulator Asoprisnil on Uterine Artery Blood Flow, Ovarian Activity, and Clinical Symptoms in Patients with Uterine Leiomyomata Scheduled for Hysterectomy

Abstract

Asoprisnil, a novel orally active selective progesterone receptor modulator, is being studied for the management of symptomatic uterine leiomyomata. The exact mechanism of action is not yet discerned. The primary objectives of this double-blind, randomized, placebo-controlled study included evaluation of the effect of asoprisnil on uterine artery blood flow. Furthermore, we assessed effects of asoprisnil on leiomyoma symptoms. Thirty-three premenopausal patients scheduled for hysterectomy due to symptomatic uterine leiomyomata were recruited in four centers and treated with 10 or 25 mg asoprisnil or placebo for 12 wk before surgery. At baseline and before hysterectomy, all patients underwent sonographic assessment to measure impedance to uterine artery blood flow, determined by resistance index and pulsatility index, as well as volumes of largest leiomyoma and uterus. In addition, patients recorded intensity and frequency of menstrual bleeding on a menstrual pictogram. Each asoprisnil treatment was compared with placebo. The increased pulsatility index in both asoprisnil groups and the statistically significantly increased resistance index within the 25-mg asoprisnil group suggest a moderately decreased uterine artery blood flow. Analysis of menstrual pictogram scores showed a statistically significant larger decrease in frequency and intensity of bleeding for both asoprisnil groups compared with placebo. Bleeding was suppressed by asoprisnil 25mg in 91% of patients. Asoprisnil treatment was well tolerated when administered daily for a 12-wk period, and no serious adverse events occurred. Asoprisnil moderately reduced uterine artery blood flow. This effect may contribute in part to the clinical effects of asoprisnil.