Treatment of erectile dysfunction due to C677T mutation of the MTHFR gene with vitamin B6 and folic acid in patients non responders to PDE5i.
BACKGROUND
Epidemiological studies conducted on erectile dysfunction (ED) have demonstrated its close correlation with cardiovascular disease. Since hyperhomocysteinemia is considered an important cardiovascular risk factor, it could also be involved in the pathogenesis of ED.


OBJECTIVE
To study the role of the C677T MTHFR mutation with subsequent hyperhomocysteinemia in the determination of ED.


METHODS
We studied 75 consecutive patients presenting with ED. Patients were interviewed using the International Index of Erectile Function. Blood samples were drawn for determination of MTHFR gene C677T mutation, homocysteine (Hcy) and folate levels. Penile color Doppler was also performed.


METHODS
Patients were administered sildenafil citrate for 2 months. The nonresponders were treated with combination of sildenafil, vitamin B6, and folic acid for 6 weeks. Patients were split into three groups, A, B, and C on the basis on their MTHFR genotype, and in a further group defined as "sildenafil nonresponders" (NR).


RESULTS
We found 20 patients homozygous for mutant MTHFR 677T, 36 heterozygous, and 19 wild type. Difference in baseline values for Hcy and folic acid was found between groups A and B, and A and C. The NR group (18 patients from group A and B), presented high levels of Hcy and low levels of folic acid. After combination treatment 16 of them (88.9%) revealed an improvement in the IIEF questionnaire. Moreover, it was measured a significant difference between the values of Hcy and folic acid at the baseline and at the end of the study for the nonresponders.


CONCLUSIONS
Hyperhomocysteinemia in patients homozygotes for the C677T mutation may interfere with erection mechanisms and thus be responsible for ED. In case of hyperhomocysteinemia associated with low levels of folates, the administration of PDE5 inhibitors may fail if not preceded by the correction of the alterated levels of Hcy and folates.
Lombardo
Francesco
F
Department of Medical Pathophysiology, University of Rome La Sapienza, Rome, Italy. lombardo@uniroma1.it
Tsamatropoulos
Petros
P
Piroli
Emanuela
E
Culasso
Franco
F
Jannini
Emmanuele Angelo
EA
Dondero
Franco
F
Lenzi
Andrea
A
Gandini
Loredana
L
D000328:Adult; D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D005492:Folic Acid / Q000627:therapeutic use*; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000235:genetics*; D018783:Impotence, Vasculogenic / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D025101:Vitamin B 6 / Q000627:therapeutic use*
D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D025101:Vitamin B 6; D005492:Folic Acid; D000068677:Sildenafil Citrate; D042965:Methylenetetrahydrofolate Reductase (NADPH2)