Effect of raloxifene and low-dose percutaneous 17β-estradiol on menopause symptoms and endometrium—A randomized controlled trial

Abstract Objective To investigate the effects on climacteric symptoms and endometrium of percutaneous low-dose 17β-estradiol associated with raloxifene in postmenopausal women. Design randomized placebo-controlled study. Method Fifty-two postmenopausal women with moderate to severe hot flushes were randomized to receive either 60 mg raloxifene (RLX; n  = 20), 0.5 mg percutaneous 17β-estradiol associated to 60 mg raloxifene (RLX + E 2 ; n  = 16) or placebo (PLC; n  = 16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and at the end of the study endometrial thickness was measured and endometrial samples were collected for histological study. Results At baseline, the mean Kupperman index was 23.7 ± 1.8 in RLX group, 22.9 ± 1.9 in RLX + E 2 group and 22.6 ± 1.9 in the placebo group (NS). After 3 months, there was a significant reduction in Kupperman index mean values in both groups, but no statistical difference was observed between groups. However, RLX + E 2 and placebo were significantly superior to RLX in reducing hot flush severity ( p Conclusions The association of percutaneous low dose of 17β-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal women, providing a safe profile in endometrium at least in short-term therapy.