Raloxifene at daily doses of 60 mg and 150 mg did not stimulate the endometrium of postmenopausal women (original) (raw)

2000, Evidence-based Obstetrics & Gynecology

OBJECTIVE To compare the uterine effects of raloxifene and estrogen in healthy postmenopausal women. DESIGN Multicentre, randomized, triple-blind, 4-arm, double-placebo-controlled trial. Allocation was by random number table, using coded medications in blocks of 4. SETTING Thirty-two centres in the USA and 1 in the UK. SUBJECTS 415 healthy postmenopausal women, aged 47-60 (mean 55) years, with a normal uterus, endometrial thickness 45 mm, serum estradiol 473 pmol/L, and lumbar spine bone mineral density in the normal range. Time since menopause was 2-8 (mean 4.6) years. INTERVENTION The women were randomized to receive daily, for 12 months, raloxifene 60 mg (n"101) or 150 mg (n"105) plus placebo, estrogen 0.625 mg plus placebo (n"100), or two placebos (n"109). All women also received calcium 520 mg daily. Transvaginal ultrasonography was performed every 3 months, and endometrial biopsy and saline-infusion sonohysterography were performed every 6 months. MAIN OUTCOME MEASURES Endometrial hyperplasia, uterine volume, endometrial thickness. MAIN RESULTS 86% of subjects underwent at least one follow-up endometrial biopsy. Endometrial hyperplasia was detected in 23/88 women (26%) in the estrogen group, 0/84 in the raloxifene 60 mg group, 0/92 in the raloxifene 150 mg group, and 2/94 (2%) in the placebo group (P(0.001). The mean endometrial thickness by transvaginal ultrasonography at baseline was 2.7 mm, with no difference among groups, and at follow-up the mean ($SD) change was 5.5$4.0 mm in the estrogen group, 0.2$1.5 mm in the raloxifene 60 mg group, 0.1$1.3 mm in the raloxifene 150 mg group, and !0.1$2.1 mm in the placebo group (P(0.001 estrogen vs other three groups, NS raloxifene groups vs placebo). Endometrial thickness '5 mm was observed in 70, 5, 4, and 6% of women, respectively. The mean uterine volume at baseline was 32 cm 3 , with no difference among groups, and at follow-up the mean change was 22$21 cm 3 with estrogen, !2$8 cm 3 with raloxifene 60 mg, !2$11 cm 3 with raloxifene 150 mg, and !3$11 cm 3 with placebo (P(0.001 estrogen vs other three groups, NS raloxifene groups vs placebo). Vaginal bleeding was reported more frequently in the estrogen group (29% of women) than in the other three groups (2-6%, P(0.001), as was mastalgia (18% vs 0-4%, P(0.001), but the withdrawal rates because of adverse events were similar among groups. CONCLUSION Raloxifene at daily doses of 60 mg and 150 mg did not stimulate the endometrium in post-menopausal women.