HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women.

ABSTRACT

OBJECTIVE: To investigate the short-term effects of HMR 3339 in comparison with raloxifene and placebo on cardiovascular risk factors. DESIGN: A multicenter, randomized, placebo-controlled, double-blind, dose-ranging study. SETTING: Gynecologic outpatient department. PATIENT(S) One hundred eighteen healthy nonhysterectomized postmenopausal women. INTERVENTION(S) Participants received daily placebo (n = 22), 2.5 mg of HMR 3339 (n = 25), 10 mg of HMR 3339 (n = 24), 50 mg of HMR 3339 (n = 24), or 60 mg of raloxifene (n = 23) for 12 weeks followed by a 2-week washout period. MAIN OUTCOME MEASURE(S) Blood concentrations of lipids measured at baseline, and after 2, 4, 8, 12, and 14 weeks, and of lipoprotein(a), homocysteine, and endothelin-1 measured at baseline, and after 4 and 12 weeks. RESULT(S) After 12 weeks of treatment with HMR 3339, compared with placebo, serum total cholesterol was reduced (10 mg of HMR 3339 -9.7%; 50 mg of HMR 3339 -15.2%), low-density lipoprotein (LDL)-cholesterol (10 mg of HMR 3339 -10.8%; 50 mg of HMR 3339 -24.2%) and plasma homocysteine concentrations (2.5 mg of HMR 3339 -3.9%; 10 mg of HMR 3339 -10.8%; 50 mg of HMR 3339 -13.8%), suggesting a dose-dependent effect of HMR 3339. These effects were already apparent after 2 weeks of treatment for total cholesterol and LDL-cholesterol, and after 4 weeks of treatment for homocysteine. After 12 weeks, raloxifene, compared with placebo, significantly decreased total cholesterol (-10.5%), LDL-cholesterol (-15.0%), and triglycerides (-16.9%), but not homocysteine. High-density lipoprotein-cholesterol, lipoprotein(a), and endothelin-1 showed no significant changes in any of the active treatment groups. CONCLUSION(S) HMR 3339 reduces total cholesterol, LDL-cholesterol, and homocysteine concentrations in postmenopausal women.