The effect of hormone replacement therapy and simvastatin on plasma homocysteine.
BACKGROUND
Homocysteine may be an independent risk factor for coronary artery disease (CAD), and the risk is at least as strong for women as for men. Homocysteine levels are lower in women compared with men, and homocysteine is lower during pregnancy and higher during menopause.


OBJECTIVE
To investigate the effects of hormone replacement therapy (HRT), simvastatin, and their combination on plasma homocysteine levels, we treated 16 postmenopausal, hypercholesterolemic women with CAD with HRT (0.625 mg conjugated equine estrogens [CEE] combined continuously with 2.5 mg medroxyprogesterone), 20 mg simvastatin, and their combination in a randomized, placebo-controlled study. Each treatment period was 8 weeks long, with a 4-week washout interval. Plasma homocysteine levels were evaluated at the end of each treatment period.


RESULTS
Only HRT, alone and in combination with simvastatin, significantly reduced homocysteine levels compared with placebo (11.82 +/- 0.74 and 12.22 +/- 0.71 vs 13.58 +/- 0.83 micromol/L, respectively, p < 0.05). Simvastatin had no effect (13.02 +/- 0.94 micromol/L), and the combination therapy was not better that monotherapy with HRT.


CONCLUSIONS
Oral HRT reduces homocysteine plasma levels, whereas simvastatin has no effect. If confirmed by randomized, prospective studies with clinical end points, HRT may be considered for women with mild hypercholesterolemia and high homocysteine levels.
Sbarouni
Eftihia
E
2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. elbee@ath.forthnet.gr
Kyriakides
Zenon S
ZS
Kremastinos
Dimitrios Th
DT
D000368:Aged; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008525:Medroxyprogesterone / Q000008:administration & dosage; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D004966:Estrogens, Conjugated (USP); D000960:Hypolipidemic Agents; D006710:Homocysteine; D019821:Simvastatin; D008525:Medroxyprogesterone