Hormone Replacement Therapy and Plasma Homocysteine Levels

Abstract

In Brief Objective To compare the effects of 4 and 12 weeks of combined estradiol-progestogen replacement with unopposed estradiol therapy on fasting plasma total homocysteine concentrations in healthy postmenopausal women. Methods In this prospective, 12-week study in healthy postmenopausal women, we randomly assigned 59 women to sequentially combined daily 2 mg estradiol (E2) plus either trimegestone 0.5 mg daily or dydrogesterone 10 mg daily (n = 28), or to unopposed daily 2 mg estradiol (n = 16), or to placebo (n = 15). Results Fasting plasma total homocysteine concentrations decreased by 9.4% in the combined estradiol-progestogen group and by 5.1% in the estradiol-only group, and they increased by 2.4% in the placebo group (analysis of covariance: combined hormone replacement therapy compared with placebo (P =.02); combined therapy compared with estradiol (P =.23); and estradiol compared with placebo (P =.26). Reductions were detectable after 4 weeks of combined estradiol-progestogen treatment. The data suggest an additional progestogen-related reduction in homocysteine levels of 0.7 μmol/L and 0.4 μmol/L after 4 and 12 weeks, respectively. Women with a baseline homocysteine concentration in the highest quartile had significantly greater reductions in homocysteine compared with women with an initial homocysteine value in the lowest quartile. Conclusion Fasting total homocysteine concentrations were significantly reduced by combined estradiol-progestogen replacement. Women with high homocysteine levels at baseline benefit the most. The progestogens used in this study did not have an unfavorable effect on homocysteine metabolism. Homocysteine concentrations are lowered 9.4% by combined estradiol-progestogen and 5.1% by unopposed estradiol therapy, and women with high levels at baseline benefit the most.