Hot flushes, experienced by 75% of menopausal women, are associated with estrogen deprivation. Estrogen was shown to ameliorate hot flushes by interacting with monoamine neurotransmitters in the brain; reducing noradrenaline and increasing serotonin. Hormone replacement therapy(HRT), the first treatment option, causes concerns over possible increased risks particularly breast cancer. Folic acid is involved in the biosynthesis of serotonin and nordrenaline, which is responsible for its effects on mood and cognition, and degrees of folate inadequacy, not severe enough to produce megaloblastic anaemia, were found to be associated with depression and cognitive malfunctioning. Also, increased age was observed to relate to reduced serum and cerebrospinal fluid folic acid levels. There is emerging evidence that folic acid supplementation ameliorates hot fl ushes by the same mechanism as estrogen. To explore this hypothesis, a multi-centre, double-blind, placebo-controlled randomized is being set up to compare the effect of 5 mg folic acid vs placebo in reducing the frequency and severity of hot fl ushes in postmenopausal women, and on the blood level of serotonin and noradrenaline. If folic acid supplementation is demonstrated to be effective, this will be a turning point in the clinical practice since it represents a cheap, safe and well-tolerated alternative to HRT. Hot flushes, experienced by 75% of menopausal women, are associated with estrogen deprivation. Estrogen was shown to ameliorate hot flushes by interacting with monoamine neurotransmitters in the brain; reducing noradrenaline and increasing serotonin. Hormone replacement therapy (HRT), the first treatment option , causes concerns over possible increased risks particularly breast cancer. Folic acid is involved in the biosynthesis of serotonin and nordrenaline, which is responsible for its effects on mood and cognition, and degrees of folate inadequacy, not severe enough to produce megaloblastic anaemia, were found To be associated with depression and cognitive malfunctioning. Also, is age evidence was follic acid supplementation ameliorates hot fl ushes by the same mechanism as estrogen. To explore this hypothesis , a multi-center, double-blind, placebo-controlled randomized is being set up to compare the effect of 5 mg folic acid vs placebo in reducing the frequency and severity of hot fl ushes in postmenopausal women, and on the blood level of serotonin and noradrenaline. If folic acid supplementation is demonstrated to be effective, this will be a turning point in the clinical practice since it represents a cheap, safe and well-tolerated alternative to HRT.