Background. Homocysteine (Hcy) is an important independent risk factor for vascular diseases. It s level is
determined by genetic polymorphism of several enzymes in association with nutritional factors. Higher Hcy levels
were found in men than in women, however the clinical significance of this phenomenon remains to be elucidated.
The aim of this study was to analyze the gender differences in Hcy levels in relation to associated factors and to
assess in which range of Hcy these differences are mainly expressed.
Methods and Results. The series comprised of 257 males and 239 females, mean age 52.9 and 52.3 years, resp.,
selected from the population study Pils II. All subjects were examined by a standard protocol, to assess clinical,
anthropometrical and laboratory variables. Hcy and methionine levels were estimated by ion exchange chromatog-
raphy, other laboratories using standard kits. The methods were validated by a reference laboratory. Statistical
analyses were done by Wilcoxon’s unpaired test and multiple linear regression.
We found in males significantly higher Hcy levels (13.1 vs. 11.5 mmol/l, p < 0.0001) than in females. This difference
persisted only in the range of normal Hcy levels (11.1, 10.2 mmol/l, p < 0.0001), i.e. up to 15 mmol/l (1st - 4th quintile
of the Hcy distribution) and not in the top quintile, considered as mild hyperhomocysteinaemia. We found in males,
with normal Hcy levels, significantly higher serum methionine (23.8 vs. 22.4 mmol/l, p < 0.0001), creatinine (91.5
vs 80.9 mmol/l, p < 0.0001) and a lower methionine/creatinine ratio (0.25 vs. 0.27, p < 0.01). Plasma folates and B12
vitamin in males were also lower than in females, however these differences were only of a borderline statistical
significance. On the other hand, in subjects with MHHcy (5th quintile) no gender differences were observed, except
Conclusions. Higher Hcy levels in males cannot be explained by differences in folate and B12 levels only. We
considered also other factors, namely higher demethylation of methionine associated with higher creatinine
production in males, which may be influenced by sex hormons.
homocysteine, gender differences, methionine, folic acid, B12, creatinine.