HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women.
OBJECTIVE
To investigate the short-term effects of HMR 3339 in comparison with raloxifene and placebo on cardiovascular risk factors.


METHODS
A multicenter, randomized, placebo-controlled, double-blind, dose-ranging study.


METHODS
Gynecologic outpatient department.


METHODS
One hundred eighteen healthy nonhysterectomized postmenopausal women.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
HMR 3339 reduces total cholesterol, LDL-cholesterol, and homocysteine concentrations in postmenopausal women.
Vogelvang
Tatjana E
TE
Project "Aging Women" and the Department of Obstetrics and Gynecology, Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, Amsterdam, The Netherlands.
Mijatovic
Velja
V
Kenemans
Peter
P
Teerlink
Tom
T
van der Mooren
Marius J
MJ
D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D017698:Postmenopause / Q000097:blood*; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D012016:Reference Values; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C495287:HMR 3339; D020845:Selective Estrogen Receptor Modulators; D006710:Homocysteine; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D002784:Cholesterol