The effect of hormone replacement therapy and simvastatin on plasma homocysteine

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. 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. 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. 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.