Effect of raloxifene on serum triglycerides in postmenopausal women: Influence of predisposing factors for hypertriglyceridemia

Background. Estrogen increases serum triglyceride (TG) levels and induces hypertriglyceridemia in susceptible women. The effect of raloxifene (RLX), a selective estrogen-receptor modulator, on serum TG has not been studied in detail. Objective: The purpose of this study was to examine the effect of RLX on serum TG levels in postmenopausal women with and without osteoporosis, including those with predisposing factors for hypertriglyceridemia. Methods: Fasting serum TG levels were assessed over 36 months in 2738 osteoporotic postmenopausal women (mean age, 67 years) assigned to placebo or RLX (60 or 120 mg/d) in an osteoporosis treatment trial and over 24 months in 1318 postmenopausal women without osteoporosis (mean age, 54 years) assigned to placebo or RLX (60 or 150 mg/d) in 3 osteoporosis prevention trials. Results: In the osteoporosis treatment trial, the median serum TG concentration decreased in all groups, but significantly more in the placebo group (placebo, -3.4%; RLX 60 mg/d, -1.4%; RLX 120 mg/d, -1.3%; P=0.002). In the osteoporosis prevention trials, the percentage change in median serum TG concentration was not significantly different among treatments (P=0.22). Among women with varying degrees of hypertriglyceridemia at baseline (>2.82, >3.39, and >4.51 mmol/L), the median serum TG level at the end of the study decreased from baseline in all groups, with no significant differences among treatments (P greater than or equal to0.13). The effect of RLX on serum TG level was not influenced by age, smoking status, use of alcohol, or presence of diabetes (P greater than or equal to0.10 for all interactions). Among women in the highest tertile of body mass index (>26.4 kg/m(2)), RLX increased serum TG levels significantly compared with placebo (placebo, -3%; RLX 60 mg/d, 6%; RLX 120 mg/d, 4%; P<0.05); the absolute increase from baseline with RLX in this sub Group was 0.05 mmol/L (4.4 mg/dL). Conclusions: RLX did not increase serum TG in postmenopausal women overall or among women with elevated TG levels or evidence of diabetes at baseline. TG levels increased slightly but statistically significantly in women in the upper tertile of body mass index who were treated with RLX.