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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

Centre for Reproductive Biology (J.Wi., H.O.D.C.) and Department of Pathology (A.R.W.W.), University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; TAP Pharmaceutical Products Inc. (K.C., C.H.), Lake Forest, Illinois 60045; Royal Infirmary (J.Wa.), Edinburgh EH16 4SA, United Kingdom; Developmental Origins of Health and Disease Division (DoHaD) (I.T.C., S.I., A.C.L.), University of Southampton, Southampton SO16 6YD, United Kingdom; Department of Obstetrics and Gynaecology (M.A.L.), University of Glasgow, Glasgow G37 2ER, United Kingdom; and Department of Obstetrics and Gynaecology (D.H.), University of Liverpool, Liverpool L8 7SS, United Kingdom

Address all correspondence and requests for reprints to: Professor Hilary O. D. Critchley, Division of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. E-mail: hilary.critchley{at}ed.ac.uk.

Introduction: 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.

Patients and Methods: 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.

Results: 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.

Conclusion: Asoprisnil moderately reduced uterine artery blood flow. This effect may contribute in part to the clinical effects of asoprisnil.

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				J. Wilkens, A.R.W. Williams, K. Chwalisz, C. Han, I.T. Cameron, and H.O.D. Critchley Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN Hum. Reprod., May 1, 2009; 24(5): 1036 - 1044. [Abstract] [Full Text] [PDF]