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RU 486: An Antiprogestin Steroid with Contragestive Activity in Women

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The Antiprogestin Steroid RU 486 and Human Fertility Control

Part of the book series: Reproductive Biology ((RBIO))

Abstract

We summarize the basic principles and the main experimental data that have led to the clinical use of RU 486’s antiprogestin activity in human fertility control (“contragestion”). The structural features of the receptor binding properties of this steroidal antihormone are reported, as well as experiments at molecular, cellular and physiological levels in rodents and primates. RU 486 (l7ß-hydroxy-llß-(4-dimethylaminophenyl-l)17α(prop-l-ynyl)-estra-4, 9-dien-3-one) is the first potent antiprogestin. Its preferential target cells are those of the endometrium or decidua; it also acts on the gonadotropic cells of the pituitary. Acting reversibly at the molecular level of receptor binding, RU 486 irreversibly interrupts target cell integrity if these cells are dependent on the continuity of progesterone action. In the case of the uterus, increased myometrium contractility and effects on the uterine cervix facilitate evacuation of the products of conception. In women, luteolysis appears to be secondary to the decrease of LH production (pituitary effect) or of hCG production, which is consequent to alteration or detachment of the trophoblast. Available clinical results indicate that RU 486 can be an efficient and safe contragestive agent, especially for the medical termination of early pregnancy, and has significant potential as a post-coital menses inducer or menstrual regulator. No significant systemic side effect has been recorded, including those events that seemed possible because of the compound’s antiglucocorticosteroid capacity. Cases of incomplete uterine evacuation after using RU 486 alone may be avoided when efficient forms of administration and/or adjunct therapy with uterotonic agents are utilized. Preliminary results obtained with the addition of a small amount of prostaglandin (which by itself would be inactive) at the end of a course of RU 486 treatment are highly satisfactory. This additive treatment may decrease the potential risk of excessive bleeding. As a drug with a twofold basis of action, physiological and molecular, the antiprogesterone RU 486 is prototypic of the second generation of methods to achieve effective control of human fertility.

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  1. Lab Hormone INSERM U33, Université de Paris Sud, 94270, Bicetre, France

    Etienne-Emile Baulieu

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  1. University of Paris-Sud, Paris, France

    Etienne-Emile Baulieu

  2. The Rockefeller Foundation, New York, New York, USA

    Sheldon J. Segal

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Baulieu, EE. (1985). RU 486: An Antiprogestin Steroid with Contragestive Activity in Women. In: Baulieu, EE., Segal, S.J. (eds) The Antiprogestin Steroid RU 486 and Human Fertility Control. Reproductive Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-1242-0_1

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  • DOI: https://doi.org/10.1007/978-1-4684-1242-0_1

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