A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels.

Abstract Objective To assess the effect of transdermal vs. oral administration of E 2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. Design Prospective, double-blind, double-dummy, placebo-controlled study. Setting Outpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. Patient(s) One hundred fifty-two healthy hysterectomized postmenopausal women. Intervention(s) Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17β-E 2 , 50 μg (n = 33), oral E 2 , 1 mg (n = 37), or oral E 2 , 1 mg, plus gestodene, 25 μg (n = 33), followed by four cycles of placebo in each group. Main outcome measure(s) Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. Result(s) Mean (±SD) homocysteine concentrations in the oral E 2 group decreased from baseline to cycle 4 (9.0 ± 2.5 μmol/L vs. 8.2 ± 2.0 μmol/L; mean change, −7.6%). Homocystine values in the oral E 2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 ± 1.6 μmol/L vs. 8.6 ± 2.0 μmol/L; mean change, −4.4%). No significant changes were observed in the transdermal E 2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. Conclusion(s) Oral E 2 therapy reduced the homocysteine concentration more than did therapy with transdermal E 2 or oral E 2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.