Objective: To compare the effects of continuous hormon replacement therapy in the form of intranasal and transdermal 17 beta-estradiol combined with dydrogesterone on serum lipids, lipoprotein(a) and apolipoproteins among postmenopausal women. Materials and methods: In this prospective study, 50 healthy postmenopausal women aged 43-54 years were randomly assigned to receive either 300 lig/day intranasal 17 beta- estradiol (n=25) or 50 mu g/day transdermal 17 beta-estradiol (n=25) for 12 weeks. All women also received 10 mg/day oral dydrogesterone continuously. At the end of the study, changes in serum total cholesterol, triglyceride, HDL, LDL, VLDL, lipoprotein(a),Apo A-I and Apo B levels within and percent changes between the groups were compared. Mann-Whitney U and Wilcoxon tests were used as indicated. P-values below 0.05 were considered significant. Results: Thirty-four women completed this study (intranasal group, n=16; transdermal group, n-18). In intranasal estradiol group, only apolipoprotein B levels were decreased significantly after 12 weeks of treatment (2.0 +/- 0.4 to 0.9 +/- 0.1, p=0.028) whereas no changes in the levels of total cholesterol, triglyceride, HDL, LDL, VLDL, lipoprotein(a) and Apo A -I were observed. Also, in transdermal estradiol group, no significant changes were seen in all variables. No significant differences with regard to variables were noted between the groups at the end of the study. Conclusions: The effects of intranasal and transdermal estradiol plus dydrogestorone as a continouos hormone replacement therapy on the serum total cholesterol, triglyceride, HDL, LDL, VLDL, lipoprotein(a) and Apo A -I levels are similar in postmenopausal women.