Continuous combined hormone replacement therapy with oral 17 beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women

Objective: To evaluate the effect of a continuous combined oral hormone rep lacement therapy (HRT) on basal and post-methionine load homocysteine level s in postmenopausal women. Design: Twenty-two postmenopausal women (PMW) were randomly allocated to re ceive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of n orethisterone acetate; n = 11) or no treatment (controls, n = 11) for 6 mon ths. A methionine oral load (0.1 g/kg body weight) was performed in each su bject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 a nd at 4, 8, and 24 h after the methionine load, while levels of vitamin B, (by high-performance liquid chromatography) and B,, and folate (both by ELI SA) were assayed in samples collected at time 0. Results: Serum levels of glucose and body mass index increased in treated P MW, whereas folate decreased in controls. In treated PMW, basal homocystein e tended to decrease (10.6 +/- 3.3 mu mol/L vs. 9.62 +/- 2.8 mu mol/L, p = 0.062), whereas in controls it significantly increased (10.7 +/- 2.65 mu mo l/L vs. 12.17 +/- 3.89 mu mol/L, p < 0.05). This increase was not significa nt after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 +/- 13.53 mu mol/L vs. 39.83 +/- 22.53 mu mol/L, p < 0.05) and 8 h ( 35.1 +/- 13.13 vs. 43.34 +/- 22.15 mu mol/L) after methionine, and integrat ed homocysteine response to methionine (392.5 +/- 133.8 mu mol/24 h vs. 458 .8 +/- 104.8 mu mol/24 h; p < 0.05), were significantly reduced in HRT-trea ted, but not in untreated, PMW. Conclusions: Continuous combined oral HRT with 17 beta -estradiol plus nore thisterone acetate reduces homocysteine levels, mainly after a methionine l oad. This effect seems to be independent of vitamin status and may have pos itive implications for the prevention of cardiovascular diseases in PMW.