Raloxifene HCl is not stimulatory in the endometrium as assessed by the blaustein criteria and an estrogenicity scoring system

Introduction: Raloxifene, a selective estrogen receptor modulator (SERM), acts as an estrogen agonist in the bone and on serum lipids and an estrogen antagonist in breast tissue. The effect of raloxifene on the endometrium of postmenopausal women is a key factor in determining its clinical application. Objectives: The objectives are to determine and compare the histologic outcomes of endometrial samples from healthy postmenopausal women receiving either a high dose of raloxifene or hormone replacement therapy (HRT). Design: The current study is a 24-month, multicenter, double-blind, randomized study of 136 healthy postmenopausal women randomized to receive either raloxifene 150 mg/day (RLX) or continuous combined HRT (Premarin® 0.625 mg/day and Provera® 2.5 mg/day). Materials and Methods: Endometrial samples obtained by Pipelle™ biopsy at baseline and endpoint were evaluated using Blaustein’s criteria (Kurman RJ, editor Blaustein’s pathology of the female genital tract. 1994), which is composed of descriptive diagnostic categories and a newly developed estrogenicity scoring system to quantify subtle morphologic changes in the postmenopausal endometrium (Boss et al. Am J Obstet Gynecol, in press). All subjects with adequate baseline and post-baseline endometrial samples were included in the analyses. The results from the 12-month interim analyses are reported and the Blaustein’s criteria and the estrogenicity scoring system are compared. Results: Overall, 95.2% of the baseline biopsies were normal. At endpoint 30.6% of the subjects in the HRT group with normal baseline biopsies developed proliferative endometrium and 2.8% developed a polyp, while none in the RLX group developed either. Histological evaluation of stromal and glandular features revealed substantially lower estrogenicity scores in the RLX group. As shown in the table, a high degree of agreement was observed between the estrogen effect grades and the Blaustein’s descriptive diagnostic categories at endpoint as shown by a Spearman correlation coefficient of 0.75 and a Kappa coefficient of 0.91. Blaustein Diagnosis (at endpoint) Estrogenicity Grade (at endpoint) Therapy Little/ None Limited Significant Marked Surface endometrium only HRT RLX 6 9 0 0 0 0 0 0 Inactive/ atrophic endometrium HRT RLX 14 19 0 1 0 0 0 0 Proliferative HRT 1 6 4 2 tissue RLX 0 1 0 0 Polyps HRT 0 1 0 0 RLX 0 0 0 0 Conclusion: Results from the 12-month interim analyses reveal that, in contrast to HRT, raloxifene does not ha