Effects of hormone replacement therapy and methylenetetrahydrofolate reductase polymorphism on plasma folate and homocysteine levels in postmenopausal Japanese women

Abstract

Objective: To evaluate the relationships among the methylenetetrahydrofolate reductase (MTHFR) polymorphism, plasma folate, total homocysteine (Hcy) levels, lipids, and the reduction of Hcy levels resulting from hormone replacement therapy (HRT). Design: Clinical study. Setting: Outpatient department of obstetrics and gynecology in a general hospital. Patient(s): Two hundred seventeen postmenopausal Japanese women. Intervention(s): Of the 217 women, 172 patients were under continuous treatment with oral conjugated equine estrogen and medroxyprogesteron acetate. Main Outcome Measure(s): Fasting Hcy, folate, methionine, lipids, and apolipoproteins were measured before and after 3 months of HRT. Result(s): The plasma Hcy concentration was significantly higher in the low folate than in the high-folate group only in patients with the homozygous (T/T) mutant. Plasma Hcy concentrations were significantly correlated with age (R = 0.64, P=.02) or years since menopause (R = 0.73, P=.02) only in the low-folate group with T/T. The plasma Hcy concentration decreased significantly in all genotypes after 3 months of HRT, but the levels of serum folate and methionine remained unchanged. Conclusion(s): The MTHFR polymorphism was associated with a higher Hcy concentration, and this association was related to the serum folate level. Hormone replacement therapy reduced the plasma Hcy concentration independently of the MTHFR polymorphism.