A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels☆
Received 21 February 2002; received in revised form 10 June 2002; accepted 10 June 2002.
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.
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.
aDepartment of Obstetrics and Gynecology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
bDepartment of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
cDepartment of Obstetrics and Gynecology, University Medical Center St. Radboud, Nijmegen, The Netherlands
dDepartment of Obstetrics and Gynecology, Diakonessenhuis, Utrecht, The Netherlands
eDepartment of Obstetrics and Gynecology, Medisch Spectrum Twente, Enschede, The Netherlands
fDepartment of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
Reprint requests: M. J. van der Mooren, M.D., Ph.D., Department of Obstetrics and Gynecology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands (FAX: 31-20-44-44-422).
☆ Supported by research grants from the Netherlands Heart Foundation (grant 95.201), Biocare Foundation (grant 96.312), and Schering AG (Berlin, Germany, grant 96.083).
ABSTRACT