Objective: This study assessed the effect of intranasal administration of 17 beta-estradiol (Aerodiol (R)) on plasma levels of homocysteine. Vitamin 1312 and folate in postmenopausal women.,Methods: In all. 26 symptomatic postmenopausal women who had undergone hysterectomy and oophorectomy at least 12 months previously participated in this 6-month randomized prospective clinical study. Menopause was determined by serum FSH level > 30 mu IU/ml and serum estradiol concentration < 30 pg/ml. Intranasal 17 beta-estradiol treatment was given once daily at a standard daily dose of 300 mu g to 16 women, and 10 did not receive any treatment.,Results: In the group receiving intranasal 17 beta-estradiol, mean (+/- S.D.) plasma homocysteine level decreased significantly from pre-treatment values (from 16.68 +/- 4.33 to 14.15 +/- 1.18 nmol/ml, p = 0.029) and the mean folate level increased (from 4.11 +/- 0.80 to 5.64 +/- 1.87 ng/ml, p = 0.012). Vitamin B12 levels showed a tendency towards increasing. In the treated group, significant negative correlations were observed between homocysteine and folate values (r = -0.586, p = 0.017) and between homocysteine and Vitamin B12 values (r = -0.672, p = 0.004). No significant changes were observed in the untreated group.,Conclusion: The reduction in plasma homocysteine levels observed after 6 months' treatment with intranasal 17 beta-estradiol may reflect an alteration in folate and Vitamin B12 homeostasis. (c) 2004 Elsevier Ireland Ltd. All rights reserved.