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

Fertil Steril. 2002 Mar;77(3):481-6. doi: 10.1016/s0015-0282(01)03228-9.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoproteins / blood
  • DNA / genetics
  • Estrogens / therapeutic use*
  • Female
  • Folic Acid / biosynthesis
  • Folic Acid / blood*
  • Homocysteine / blood*
  • Hormone Replacement Therapy*
  • Humans
  • Japan
  • Lipids / blood
  • Medroxyprogesterone Acetate / therapeutic use*
  • Methionine / blood
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Progesterone Congeners / therapeutic use*
  • Regression Analysis


  • Apolipoproteins
  • Estrogens
  • Lipids
  • Progesterone Congeners
  • Homocysteine
  • DNA
  • Folic Acid
  • Methionine
  • Medroxyprogesterone Acetate
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)