The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial.
C-Reactive protein and homocysteine are independent risk factors for the development of cardiovascular disease. This study compared the effects of hormone replacement therapy (HRT) and raloxifene on serum C-reactive protein and homocysteine levels as markers of cardiovascular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, placebo-controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo for 6 months. C-Reactive protein and homocysteine were measured in baseline and 6-month serum samples. HRT increased C-reactive protein levels by 84% (P<0.001), whereas raloxifene (60 and 120 mg/day) had no significant effect (-6% and -4%;, respectively; P>0.2). Raloxifene (60 and 120 mg/day) significantly lowered serum levels ofhomocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained with HRT. We conclude that HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women. Whereas cardiovascular risk predicted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.
Walsh
B W
BW
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. bwwalsh@bics.bwh.harvard.edu
Paul
S
S
Wild
R A
RA
Dean
R A
RA
Tracy
R P
RP
Cox
D A
DA
Anderson
P W
PW
D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012307:Risk Factors
D008055:Lipids; D006710:Homocysteine; D020849:Raloxifene Hydrochloride; D005340:Fibrinogen; D002097:C-Reactive Protein