This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, A. Articles by Baird, D. T. Search for Related Content PubMed PubMed Citation Articles by Brown, A. Articles by Baird, D. T.

Daily Low-Dose Mifepristone Has Contraceptive Potential by Suppressing Ovulation and Menstruation: A Double-Blind Randomized Control Trial of 2 and 5 mg per Day for 120 Days

Contraceptive Development Network (A.B., D.T.B.), Centre for Reproductive Biology, University of Edinburgh, Edinburgh, EH3 9ET United Kingdom; and Shanghai Institute of Family Planning Technical Instruction (L.C., S.L.), International Peace Maternity and Child Health Hospital, China Welfare Institute, Shanghai 200030, People’s Republic of China

Address all correspondence and requests for reprints to: Prof. D. T. Baird, Contraceptive Development Network, Centre for Reproductive Biology, University of Edinburgh, 37 Chalmers Street, Edinburgh, EH3 9ET United Kingdom. E-mail: cdn{at}ed.ac.uk

Daily administration of progesterone (P) antagonists to women inhibits ovulation and disrupts endometrial function. In this double-blind randomized trial, we have explored the contraceptive potential of two doses of the P antagonist mifepristone in healthy volunteers in Edinburgh and Shanghai.

Ninety-eight women (58 in Edinburgh and 40 in Shanghai) were randomized to receive either 2 or 5 mg mifepristone daily for 120 d. Ovarian activity was monitored by the weekly measurement of steroid metabolites in urine and of E2 and P in plasma every month. Endometrial function was assessed by menstrual records, and ultrasound measurement of endometrial thickness was assessed every month. Endometrial biopsy was collected on d 12 of the control cycle and after 60 and 120 d of treatment.

Ninety women (50 in Edinburgh and 40 in Shanghai) completed the study. Follicular activity continued during treatment with both doses in Edinburgh women, although ovulation was suppressed in the majority of cycles (90 and 95% of cycles in 2- and 5-mg groups, respectively). The women in Shanghai showed evidence of ovulation in only 3 of 160 months of treatment (2 in 2-mg group and 1 in 5-mg group). The majority of women in both centers were amenorrheic (65% in 2-mg group and 88% in 5-mg group in Edinburgh, and 90% in both dose groups in Shanghai). The endometrial thickness increased significantly in women in Edinburgh and decreased in Shanghai; histology showed either atrophic or cystic changes without evidence of hyperplasia. There was no pregnancy reported in the 200 months of exposure in 50 sexually active women who had used no other method of contraception during the study.

We conclude that mifepristone in low daily doses inhibits ovulation and induces amenorrhea in the majority of women and has the potential to be developed as a novel estrogen- free oral contraceptive pill.

This work was supported by Grant G9523250 to the Contraceptive Development Network.

Abbreviations: COC, Combined oral contraceptive; Cr, creatinine; E₁G, estrone glucuronide; P, progesterone.

This article has been cited by other articles:

				J. Wilkens, K. Chwalisz, C. Han, J. Walker, I. T. Cameron, S. Ingamells, A. C. Lawrence, M. A. Lumsden, D. Hapangama, A. R. W. Williams, et al. 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 J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4664 - 4671. [Abstract] [Full Text] [PDF]

				F. M. Horne and D. L. Blithe Progesterone receptor modulators and the endometrium: changes and consequences Hum. Reprod. Update, November 1, 2007; 13(6): 567 - 580. [Abstract] [Full Text] [PDF]

				N. Chabbert-Buffet, A. Pintiaux-Kairis, P. Bouchard, and on behalf of the VA2914 Study Group Effects of the Progesterone Receptor Modulator VA2914 in a Continuous Low Dose on the Hypothalamic-Pituitary-Ovarian Axis and Endometrium in Normal Women: A Prospective, Randomized, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3582 - 3589. [Abstract] [Full Text] [PDF]

				F. Lakha, P.C. Ho, Z.M. Van der Spuy, K. Dada, R. Elton, A.F. Glasier, H.O.D. Critchley, A.R.W. Williams, and D.T. Baird A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel) Hum. Reprod., September 1, 2007; 22(9): 2428 - 2436. [Abstract] [Full Text] [PDF]

				N. Narvekar, H. O.D. Critchley, L. Cheng, and D. T. Baird Mifepristone-induced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal vascular endothelial growth factor Hum. Reprod., September 1, 2006; 21(9): 2312 - 2318. [Abstract] [Full Text] [PDF]

				J. K. Jain, A. Li, W. Yang, P. Minoo, and J. C. Felix Effects of mifepristone on proliferation and apoptosis of human endometrium in new users of medroxyprogesterone acetate Hum. Reprod., March 1, 2006; 21(3): 798 - 809. [Abstract] [Full Text] [PDF]

				H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley Endocrine Regulation of Menstruation Endocr. Rev., February 1, 2006; 27(1): 17 - 46. [Abstract] [Full Text] [PDF]

				N. Chabbert-Buffet, G. Meduri, P. Bouchard, and I. M. Spitz Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications Hum. Reprod. Update, May 1, 2005; 11(3): 293 - 307. [Abstract] [Full Text] [PDF]

				K. Chwalisz, W. Elger, T. Stickler, C. Mattia-Goldberg, and L. Larsen The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women Hum. Reprod., April 1, 2005; 20(4): 1090 - 1099. [Abstract] [Full Text] [PDF]

				N. Narvekar, S. Cameron, H. O. D. Critchley, S. Lin, L. Cheng, and D. T. Baird Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2491 - 2497. [Abstract] [Full Text] [PDF]

				E. C. Raney and J. Methot Recent Advances in Hormonal and Barrier Contraception Journal of Pharmacy Practice, June 1, 2003; 16(3): 209 - 217. [Abstract] [PDF]

				D.T. Baird, A. Brown, H.O.D. Critchley, A.R. Williams, S. Lin, and L. Cheng Effect of long-term treatment with low-dose mifepristone on the endometrium Hum. Reprod., January 1, 2003; 18(1): 61 - 68. [Abstract] [Full Text] [PDF]

				S.M. Borman, K.M. Schwinof, C. Niemeyer, K. Chwalisz, R.L. Stouffer, and M.B. Zelinski-Wooten Low-dose antiprogestin treatment prevents pregnancy in rhesus monkeys and is reversible after 1 year of treatment Hum. Reprod., January 1, 2003; 18(1): 69 - 76. [Abstract] [Full Text] [PDF]