Objective: To examine endometrial response to long-term low-does RU486 administration.
Design: Retrospective controlled study of women with endometriosis treated for 6 months with 50 mg RU486 daily for 6 months. Controls consisted of women in the follicular phase of a spontaneous cycle undergoing endometrial biopsy.
Setting: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center.
Patients and interventions: Nine patients treated with long-term low-dose RU486 and nine normal cycling controls undergoing hysterectomy or endometrial biopsy for benign disease.
Main outcome measures: Changes in endometrial morphology and immunohistochemical analysis for estrogen receptor (ER) and progesterone receptor (PR) protein.
Results: All patients treated with RU486 exhibited abnormal endometrial morphology. The endometrial glands were irregular in size and shape. The stroma was varied but consisted predominantly of dense cellular stroma with frequent mitotic figures. The glands were lined by a combination of epithelial types some of which were secretory. No cytologic atypia was seen. Levels of ER immunoreactivity, as determined by image analysis, were greater in the stroma with no difference in PR immunoreactivity compared with controls. No difference in ER and PR immunoreactivity were seen in the glands compared with normal controls.
Conclusion: The generalized cystic changes demonstrated are consistent with a chronic unopposed estrogen effect and are concordant with hormonal data showing early to midfollicular phase levels of estrogens. They also are consistent with our findings of increased ER immunoreactivity in the stroma. Evidence of minimal P agonist effect was noted.
PIP: At the University of California, San Diego, Medical Center during laparoscopy, reproductive specialists examined samples of endometrial tissue from 9 women being treated for endometriosis with 50 mg/day of RU-486 for 6 months and from 9 untreated women (controls) in the follicular phase of the cycle to determine whether or not low-dose RU-486 affected the endometrium. All 9 women treated with RU-486 had abnormal endometrial morphology. Mild hyperplasia was evident in the functional tissues, especially in the stromal compartment. The cellular stroma were dense and had many mitotic figures. The shape of endometrial glands was not regular in size or shape. RU-486 patients exhibited significantly more estrogen receptor (ER) immunostaining than controls (122.93 vs. 103.2; p 0.002), but progesterone receptor (PR) immunostaining was essentially the same. On the other hand, there were no differences in ER and PR in the endometrial glands. These findings suggest that RU-486 acts as a progesterone antagonist and has a chronic unopposed estrogen effect. They also show that the effect of RU-486 is associated with early to midfollicular phase levels of estrogens.