Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine levels in 121 perimenopausal women free of cardiovascular disease, and recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17β-estradiol and desogestrel (17βE2-D) and the placebo group and open with respect to a combination of conjugated equine estrogens and norgestrel (CEE-N). At baseline and after 6 months, fasting serum homocysteine levels were measured. Differences in 6 months serum homocysteine levels from baseline between treatment and placebo groups were calculated, and expressed as a percentage of the 6 months placebo level. After 6 months, the difference in serum homocysteine levels between women receiving 17βE2-D and placebo was -6.3% (95% CI, -12.4%; 0.0%, P=0.06). The difference between women receiving CEE-N and placebo was -10.1% (95% CI, -16.7%; -2.9%, P<0.01). The difference between the combined group of both types of hormone replacement therapy users and placebo was -7.8% (95% CI, -13.2%; -2.0%, P=0.01). No significant difference was observed between the two active regimens. Our results indicate that hormone replacement therapy decreases homocysteine levels in perimenopausal women.

Cardiovascular disease, Estradiol, Homocysteine, Hormone replacement therapy, Women,
Erasmus MC: University Medical Center Rotterdam

Hak, A.E, Bak, A.A.A, Lindemans, J, Planellas, J, Coelingh-Bennink, H.J.T, Hofman, A, … Witteman, J.C.M. (2001). The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women: A randomized controlled trial. Atherosclerosis, 158(2), 437–443. doi:10.1016/S0021-9150(01)00449-X