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 E₂ 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-E₂, 50 μg (n = 33), oral E₂, 1 mg (n = 37), or oral E₂, 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 E₂ 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 E₂ 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 E₂ group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups.

Conclusion(s)

Oral E₂ therapy reduced the homocysteine concentration more than did therapy with transdermal E₂ or oral E₂ plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.

Keywords:  Transdermal, hormone replacement therapy, estrogen, gestodene, homocysteine, placebo