Mifepristone: where do we come from and where are we going? Clinical development over a quarter of a century

• Published in: Contraception (Stoneham) 2010-11, Vol.82 (5), p.442-452
• Main Author: Spitz, Irving M
• Format: Article
• Language: English
• Subjects: Abortifacient Agents, Steroidal - administration & dosage; Abortifacient Agents, Steroidal - adverse effects; Abortifacient Agents, Steroidal - pharmacology; Abortion, Legal; Animals; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - pharmacology; Contraceptives, Postcoital, Synthetic - administration & dosage; Contraceptives, Postcoital, Synthetic - adverse effects; Contraceptives, Postcoital, Synthetic - pharmacology; Female; Genital Diseases, Female - drug therapy; Humans; Mifepristone - administration & dosage; Mifepristone - adverse effects; Mifepristone - pharmacology; Pregnancy; Receptors, Progesterone - agonists; Receptors, Progesterone - antagonists & inhibitors; Women's Health
• ISSN: 1879-0518
• DOI: 10.1016/j.contraception.2009.12.012

Administration of mifepristone followed by the prostaglandin, misoprostol, has been used successfully in the medical termination of pregnancy for over 25 years, and the method is registered in 35 countries. Single doses of mifepristone are also effective as an emergency postcoital contraceptive. Mifepristone administered for 3 months or longer to women with uterine leiomyomas, is associated with a reduction in pain and bleeding with improvement in quality of life and decrease in fibroid size. Mifepristone is also effective in decreasing pain in women with endometriosis. In both these conditions, serum estradiol levels are in the range of those in the early follicular phase. A daily dose of at least 2 mg mifepristone blocks ovulation. In contrast, weekly administration of 25 or 50 mg does not consistently block ovulation but has contraceptive potential by delaying endometrial development. Mifepristone in a dose of 200 mg, administered 48 h after the Luteinizing Hormone (LH) surge, also acts as a contraceptive, but this strategy is not practical for widespread use. Administration of mifepristone for 4-6 months or longer may lead to endometrial thickening. Endometrial histology reveals cystic glandular dilation together with admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histological pattern does not represent endometrial hyperplasia.