Effect of oral or transdermal hormone replacement therapy on homocysteine levels: a randomized clinical trial

Objective: Aim of this randomized trial was evaluate the effect on homocysteine plasma levels of two different hormone replacement therapy (HRT) formulations in a group of late postmenopausal women. Methods: Eligible for this study were women: in postmenopause since 5 years or more (confirmed from FSH level greater than or equal to40 mIU/I); with body mass index (BMI) less than or equal to35; without endocrine, hepatic or renal diseases; not current users of vitamin B or folic acid supplements; not users of any lipid-lowering drugs and sex steroids in the 6 months before trial entry. Group A: oral estradiol valerate 2 mg per day per oral normegestrol acetate 2.5 mg per day (n = 98) for 12 months; Group B: a weekly patch releasing estradiol (50 mug per day) per oral normegestrol acetate 2.5 mg per day (n = 10 1) for 12 months. Results: The mean values of the homocysteine levels in the group A and B at baseline, 3, 6 and 12 months were 7.9 and 9.1, 8.7 and 8.9, 9.3 and 10.2, 9.6 and 10.2, respectively, the differences between the two treatments were not statistically significant (time by treatment interaction, P = 0.32). Otherwise, the changes of homocysteine level at the four visits was statistically significant (P = 0.0001) in both groups. In particular, in the oral treatment group homocysteine levels increased from baseline of 10.5% at 3 months, of 17.2% after 6 months of therapy and of 21.9% at the end of the study; in the transdermal group, after a little decrease at 3 months (1.5%), the increases were of 12.1 and 12.9%, respectively. Conclusions: This study does not show any different effect of oral and transdermal treatment with estradiol plus normegestrol acetate on homocysteine levels. Further it does not support previous suggestion of a lowering effect of HRT on plasma homocysteine. (C) 2003 Elsevier Ireland Ltd. All rights reserved.