Clinical utility of progesterone receptor modulators and their effect on the endometrium.
OBJECTIVE
In view of the spate of recent publications related to mifepristone and some second generation progesterone receptor modulators (PRMs), this appears to be an opportune time to view the clinical status of these compounds.


RESULTS
Randomized double-blind placebo-controlled trials have been conducted with mifepristone, CDB-4124 (Proellex), CDB-2914 (VA 2914, Ulipristal) and asoprisnil (J867). All these PRMs are effective in the treatment of uterine fibroids where they are associated with a reduction in pain, bleeding and improvement in quality of life and decrease in fibroid size. CDB-4124 is also efficacious in endometriosis. Long-term treatment with PRMs may be associated with endometrial thickening on ultrasound and there have been reports of endometrial hyperplasia. Several reassuring recent publications have done much to explain the mechanism underlying these endometrial changes. The most common histological finding is cystic glandular dilatation often associated with both admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histology has not been previously encountered in clinical practice and should not be confused with endometrial hyperplasia. The endometrial thickness is related to this cystic glandular dilatation.


CONCLUSIONS
At this stage of development, PRMs cannot be administered for longer than 3 or 4 months. Even over this time, there is improvement of symptoms associated with fibroids and endometriosis. Clinicians and pathologists need to be aware that the endometrial thickening and histological appearance do not represent endometrial hyperplasia.
Spitz
Irving M
IM
Institute of Hormone Research and Ben Gurion University of the Negev, Jerusalem, Israel. Irving@spitz.com
D004334:Drug Administration Schedule; D004715:Endometriosis / Q000188:drug therapy / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology*; D004963:Estrenes / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000473:pathology; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D009649:Norpregnadienes / Q000008:administration & dosage / Q000494:pharmacology; D010091:Oximes / Q000008:administration & dosage / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D011980:Receptors, Progesterone / Q000187:drug effects*; D013997:Time Factors; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000473:pathology
D004963:Estrenes; D006727:Hormone Antagonists; D009649:Norpregnadienes; D010091:Oximes; D011980:Receptors, Progesterone; C461063:telapristone acetate; D015735:Mifepristone; C094854:ulipristal; C488516:asoprisnil