Investigational developments for the treatment of progesterone-dependent diseases.
BACKGROUND
Clinical evidence has shown that conditions such as uterine fibroids, endometriosis and breast cancer are progesterone-dependent diseases. Therefore, progesterone receptor (PR) antagonists and selective PR modulators (SPRMs) are under development for the treatment of these conditions. However, the first PR antagonists that became available exhibit insufficient selectivity or tolerability for the chronic administration required to treat these conditions. Despite initial setbacks, development of second-generation PR antagonists with better selectivity continues forward.


OBJECTIVE
In this review we would like to summarise prospects for using PR antagonists for the treatment of uterine fibroids, endometriosis and breast cancer, and to give an overview of the development of new steroidal and non-steroidal PR antagonists.


METHODS
Available preclinical and clinical data and publications have been reviewed with the focus on scientific background and use in the three mentioned indications.


CONCLUSIONS
Preclinical and clinical evidence demonstrated that PR antagonists and SPRMs are effective for the treatment of progesterone-dependent diseases. Future development will demonstrate if they can become important drugs.
Möller
Carsten
C
Bayer Schering Pharma, Global Drug Discovery, Women's Healthcare, Müllerstrasse 178, 13353 Berlin, Germany.
Hoffmann
Jens
J
Kirkland
Thomas A
TA
Schwede
Wolfgang
W
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D054333:Drug Partial Agonism; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D006727:Hormone Antagonists; D008024:Ligands; D011980:Receptors, Progesterone; D011374:Progesterone