Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study.
OBJECTIVE
To compare the effects of the selective estrogen receptor modulator (SERM) raloxifene (Evista) and a continuous combined hormone replacement therapy (ccHRT) formulation containing estradiol and norethisterone acetate (Kliogest) on lipid and fibrinogen levels of postmenopausal women.


METHODS
Euralox 1 was a prospective, randomized, double-blind trial. After a placebo wash-out, healthy postmenopausal women (n = 1008, average age 56.1 +/- 4.9 years) with a health risk profile that suggested a potential benefit from either treatment were randomly assigned to either 60 mg raloxifene or ccHRT consisting of 2 mg estradiol and 1 mg norethisterone acetate (NETA) per day for 6 months.


METHODS
Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol with its fractions HDL2 and HDL3, the LDL/HDL ratio, triglycerides and fibrinogen were assessed at baseline and after 6 months or on early drop-out.


RESULTS
Baseline values were comparable between the two groups. Blood samples of 841 women (83.4%) were available at baseline and endpoint. Total and LDL cholesterol decreased statistically significantly from baseline to endpoint in both treatment arms (by 7.2% and 3.8% with raloxifene and by 13.0% and 8.9% with ccHRT, respectively). Raloxifene produced a statistically significant increase in HDL cholesterol by 4.2%, while ccHRT induced a decline by 9.5%. Triglycerides were moderately suppressed with raloxifene and ccHRT, by 3.6 and 5.4%, respectively. Fibrinogen fell by 7.0% with raloxifene and rose by 3.6% with ccHRT.


CONCLUSIONS
Continuous combined HRT was associated with decreases in total cholesterol and LDL cholesterol about twice as large as with raloxifene, but also with a decrease in HDL cholesterol. The smaller decreases in total cholesterol and LDL cholesterol associated with raloxifene were accompanied by an increase in HDL cholesterol and a decrease in fibrinogen. In conclusion, raloxifene affects fibrinogen concentrations and the overall cholesterol profile more favorably than ccHRT; these differences may have important implications for the reduction of cardiovascular disease.
Nickelsen
T
T
Eli Lilly and Company, Bad Homburg, Germany.
Creatsas
G
G
Rechberger
T
T
Depypere
H
H
Erenus
M
M
Quail
D
D
Arndt
T
T
Bonnar
J
J
D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005060:Europe; D005260:Female; D005340:Fibrinogen / Q000187:drug effects; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077563:Norethindrone Acetate; D017698:Postmenopause; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D005340:Fibrinogen; D002784:Cholesterol; D000077563:Norethindrone Acetate; D009640:Norethindrone