Might erectile dysfunction be due to the thermolabile variant of methylenetetrahydrofolate reductase?

J Endocrinol Invest. 2004 Oct;27(9):883-5. doi: 10.1007/BF03346286.


Hyperhomocysteinemia is considered one of the most important cardiovascular risk factors increasing considerably the risk of stroke and myocardial infarction. With respect to endothelial function, direct effects of hyperhomocysteinemia on vascular endothelial cells have been demonstrated through the reduction of endothelial nitric oxide production. In this paper, we report the case of a young man with homozygote genotype mutated with 5-methylenetetrahydrofolate reductase (MTHFR) thermolabile variant who, in the absence of relational stress, developed an erectile dysfunction (ED) refractory to the vasoactive type-V phosphodiesterase (PDE5) inhibitor therapy. After one month of treatment with 5 mg/day folic acid and 1000 microg/day cyanocobalamin, the patient restarted the assumption of 50 mg sildenafil, obtaining satisfying erections during sexual intercourse. We suggest that hyperhomocysteinemia may interfere with penile blood supply and, thus, be responsible for ED. If this relationship is confirmed, plasma levels and urinary homocysteine (HCy) should be evaluated in selected young patients with vascular ED. Furthermore, careful attention should be given to the risk of ED when dealing with this metabolic disturbance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Administration Schedule
  • Drug Stability
  • Drug Therapy, Combination
  • Erectile Dysfunction / drug therapy
  • Erectile Dysfunction / genetics*
  • Folic Acid / administration & dosage
  • Folic Acid / therapeutic use
  • Genetic Variation*
  • Genotype
  • Hematinics / administration & dosage
  • Hematinics / therapeutic use
  • Homozygote
  • Hot Temperature
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / chemistry*
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Mutation
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / therapeutic use
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use
  • Purines
  • Retreatment
  • Sildenafil Citrate
  • Sulfones
  • Treatment Failure
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / therapeutic use


  • Hematinics
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Folic Acid
  • Sildenafil Citrate
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12