Objective To evaluate the effect of two different hormone therapy (HT) doses on fasting and post-methionine homocysteine levels, an independent risk factor for cardiovascular and thromboembolic diseases. Methods Forty-eight women in natural postmenopause randomly received calcium 1mg/day (control group; n=12) or calcium plus low dose (1mg estradiol plus 0.5 mg norethisterone; n=18) or high dose (2mg estradiol plus 1mg norethisterone; n=18) HT in a 6-month randomized, controlled, prospective study. Results Folate levels did not vary in any group, while levels of vitamin B12 significantly decreased after low (-12.2 +/- 6.6%; p < 0.04) or high-dose HT (- 13.9 +/- 6.1%; p < 0.01). Fasting homocysteine was reduced by either HT dose in a way that was inversely related to pretreatment homocysteine levels (-0.675x; r=0.644; p < 0.0001). Modification of post-load homocysteine increase was influenced by the HT dose and inversely related to the homocysteine response to methionine observed at baseline. The regression slope observed with the low-dose HT (-1.637x; r=0.57; p < 0.02) was significantly steeper (p < 0.001) than that observed with the high-dose HT (-0.304x; r=0.554; p < 0.03) dose. Conclusions Low- or high-dose HT similarly influences fasting homocysteine levels. Low-dose HT seems to be more effective than high-dose HT in reducing the post-methionine homocysteine increase.
