Reversal of Progesterone Receptor Modulator Associated Endometrial Changes upon Completion of a Withdrawal Bleed
OB Ioffe, RJ Zaino, GL Mutter. University of Maryland School of Medicine, Baltimore, MD; Hershey Medical Center, Hershey, PA; Brigham and Women's Hospital, Boston, MA
Background: Selective progesterone receptor blockers such as CDB-4124 (ProellexTM) administered for treatment of fibroids or endometriosis produce an altered endometrium including irregular cysts and non-physiologic combinations of glandular secretion, mitotic activity, and apoptosis that we have previously designated “PAEC”1. This study examined endometrial histology during and following treatment with oral CDB-4124 to determine if these changes are reversible.
Design: 19 premenopausal women taking 12.5 to 25mg daily CDB-4124 had endometrial biopsies during treatment, and post-treatment biopsy. Endometrial slides were blindly examined by each of 3 pathologists, and scored as “PAEC” when cysts, combined with one or more of the PAEC associated epithelial types (seroid differentiation, secretory with mitoses, mixed phase) were present.
Results: 16/19 patients had adequate biopsies, with a median interval of 91 days between last drug administration and followup biopsy (range 41-351, mean=135 days). Of these, 69% (11/16) showed PAEC changes while on therapy. PAEC changes resolved in 91% (10/11), showing secretory (6/10), proliferative (3/10) or atrophic (1/10) endometrium. One patient (age 50) with PAEC changes did not menstruate upon agent withdrawal, and she had PAEC changes 102 days after discontinuing therapy.
Conclusions: Conclusion: Across the varied conditions studied, discontinuation of Proellex administration and completion of withdrawal endometrial shedding reversed pre-existing PAEC changes in the majority (91%) of cases. Failure to complete a withdrawal shedding may occur in older patients as they approach the perimenopause, and this can be associated with retention of PAEC changes. Reference List 1. Ioffe OB, Zaino RJ, Mutter GL. Endometrial changes from short term therapy with CDB-4124, a selective progesterone receptor modulator. Mod Path 2009; 22:450-459.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 117, Wednesday Morning