Effects of Raloxifene Combined with Low-dose Conjugated Estrogen on the Endometrium in Menopausal Women at High Risk for Breast Cancer

Abstract

OBJECTIVES: To compare the effects of low-dose conjugated estrogen (CE), raloxifene, and the combination thereof on the endometrium of postmenopausal women. METHODS: Postmenopausal women between 45 and 60 years of age, with Gail score≥1.67 and no endometrial disorders, were randomly assigned to receive low-dose CE (0.3 mg), raloxifene (60 mg), or combined therapy for 1 year. Transvaginal ultrasound was performed at baseline and every 3 months; the Kupperman Index was assessed at baseline and every 6 months. Endometrial biopsies were performed if endometrial thickness (ET) was ≥5 mm or if vaginal bleeding occurred. The primary outcome was the occurrence of ET≥5 mm over the one-year period. RESULTS: Seventy-three women were randomly assigned and analyzed on an intent-to-treat basis. Eight, three, and four women in the CE, raloxifene, and combination groups, respectively, exhibited ET≥5 mm. No genital bleeding was reported in the combination group. Endometrial biopsy revealed atrophy or polyps in all groups, with one patient in the CE group exhibiting a proliferative endometrium without atypia. At 6 months, there was a progressive increase in mean ET in the CE group, but not in the other two groups, with statistically significant differences at 6, 9, and 12 months. Mean scores for vasomotor symptoms and Kupperman Index favored the CE and combination groups over raloxifene. CONCLUSION: Combined raloxifene and low-dose CE decreased the severity of menopausal symptoms to a similar extent as CE alone and had similar effects as raloxifene alone on the endometrium.

Estrogen Receptor Function: Impact on the Human Endometrium

“…The antagonistic effect of raloxifene on estradiol-treated endometrial epithelial Ishikawa cells has been demonstrated by the altered expression of genes such as HOXA 10, leukemia inhibitory factor, PR, and EMX2 (150). Notably, raloxifene does not exhibit the endometrial side effects observed with tamoxifen (151,152). In estrogen-stimulated ovariectomized rat surgical models of endometriosis, treatment with 10 mg/kg raloxifene for 7 to 14 days resulted in reduced uterine volumes (153).…”

Article Review: Biochemical Aspect of Survivin Hormone

“…Using RNA obtained from proliferative (n = 7) or secretory (n = 5) stage endometrial biopsy, QPCR testing was used to ascertain whether the survivin gene is actually transcribed inside the cyclic human endometrium [70] . Cell proliferation endometrium samples showed almost 50-fold greater levels of survivin gene activity than secretion ones (median proliferative=4•08, median secretory=0•08; P=0•01; Figure 3).…”