The effect of estrogen replacement therapy on total plasma homocysteine in healthy postmenopausal women

Objective: To clarify the effect of estrogen on total plasma homocysteine concentration and on the concentration of vitamins required for homocysteine metabolism (folate, vitamin B-12, and vitamin B-6). Methods and Results: We measured total fasting plasma homocysteine in 16 healthy postmenopausal women before and 6 hours after a methionine load (100 mg/kg); fasting concentrations of folate, vitamin B-12, vitamin B-6, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were also determined. After 6 months of estrogen replacement therapy with estradiol, 2 mg daily, and I cycle of quarterly methoxyprogesterone acetate, 5 mg daily administered on the 91st through 100th days, measurements were repeated. There was no significant change in mean +/-SD fasting homocysteine concentration (8.8+/-2.5 vs 8.5+/-2.0 mu mol/L; P=.30); homocysteine concentrations after methionine load increased from 38.8+/-12.3 to 51.1+/-12.5 mu mol/L (P=.01). During this time period, no significant changes occurred in the concentrations of folate (11.7+/-4.4 vs 9.8+/-4.1 nmol/L; P=.06), vitamin B-12 (393+/-182 vs 411+/-155 pmol/L; P=.40), or vitamin B-6 (pyridoxal phosphate) (26+/-21 s 36+/-25 nmol/L; P=.15), The mean +/-SD concentration of low-density cholesterol declined 20% (from 147+/-32 to 118+/-37 mg/dL) and high-density lipoprotein increased 16% (from 40+/-13 to 46+/-19 mg/dL) during the study period. Conclusions: Sis months of estrogen replacement therapy did not lower fasting plasma total homocysteine concentrations and raised homocysteine concentrations following a methionine load. Lipid profiles improved significantly during the study period. A reduction in homocysteine concentrations is not likely to contribute to the reduction in cardiovascular events seen with estrogen replacement therapy.