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Human Reproduction Update Advance Access originally published online on March 24, 2005
Human Reproduction Update 2005 11(3):293-307; doi:10.1093/humupd/dmi002
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications

Nathalie Chabbert-Buffet1,3,5, Geri Meduri2, Philippe Bouchard3 and Irving M. Spitz4

1 Vascular Medicine Unit, Tenon Hospital APHP, 4 rue de la Chine, F 75020 Paris, 2 Hormonal Biochemistry Unit, Molecular Pharmacology of Progesterone Group, Bicêtre Hospital, APHP, 74 rue du Général Leclerc, F 94 000 Bicêtre, 3 Endocrinology Unit and EA 1533, University Pierre et Marie Curie, Genetics of Human Reproduction, St Antoine Hospital APHP, 184 rue du Fg St Antoine, F 75012 Paris, France and 4 Institute of Hormone Research, P.O.Box 3235, Jerusalem 91031, Israel

5 To whom correspondence should be addressed at: Vascular Medicine Unit, Tenon Hospital APHP, 4 rue de la Chine, F 75020 Paris, France. Email: nathalie.chabbert-buffet{at}tnn.ap-hop-paris.fr

Since the discovery of the antiprogestin mifepristone, hundreds of similar compounds have been synthesized, which can be grouped in a large family of progesterone receptor ligands. This family includes pure agonists such as progesterone itself or progestins and, at the other end of the biological spectrum, pure progesterone receptor antagonists (PA). Selective progesterone receptor modulators (SPRM) have mixed agonist–antagonist properties, and occupy an intermediate position of the spectrum. These compounds have numerous applications in female health care. Mifepristone is used to terminate pregnancy, and as such is commercially available in many countries. The negative abortion-related image of mifepristone has clearly limited the involvement of the major pharmaceutical companies in the development of PA and SPRM. Many PA and SPRM display direct antiproliferative effects in the endometrium, although with variable actions which seem product- and dose-dependent. This property justifies their use in the treatment of myomas and endometriosis. PA also suppress late follicular development, block the LH surge and retard endometrial maturation, which renders them potential estrogen-free contraceptive drugs. SPRM such as asoprisnil are not as effective in blocking the LH surge and appear to target the endometrium directly and produce amenorrhoea. Interestingly, clinical data show that treatment with these compounds is not associated with hypo-estrogenism and bone loss. The potential clinical applications of these compounds cover a broad field and are very promising in major public health areas. These include emergency contraception, long-term estrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), myomas (where they induce a marked reduction in tumour volume and produce amenorrhoea) and endometriosis. Further developments might also include hormone replacement therapy in post-menopausal women, as well as the treatment of hormone-dependent tumours.

Key words: contraception / mifepristone / myomas / progesterone receptor antagonists / selective progesterone receptor modulators


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