Plasma homocysteine in women taking hormone replacement therapy: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial

Elevated plasma homocysteine levels have been associated with increased atherosclerotic disease risk. Estrogen and estrogen/progestin replacement therapy have been suggested to lower plasma homocysteine levels in postmenopausal women. To assess the impact of hormone replacement therapy (HRT) on plasma homocysteine, levels were measured in samples from adherent women randomized to placebo (n = 34), conjugated equine estrogens (n = 36), or continuous conjugated equine estrogens + progestin (n = 33) in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. Homocysteine levels decreased between baseline and follow-up (12 and 36 months) in all treatment groups. The magnitude of the reduction was greater in the conjugated estrogens group at 12 months compared with placebo (p = 0.036), even when adjusted for folate and B vitamin consumption, but this difference did not persist at 36 months. These data suggest that estrogen therapy has a modest, but transient, impact on plasma homocysteine levels in women with normal homocysteine at baseline.