title: 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.
  
  
  METHODS
  Prospective, double-blind, double-dummy, placebo-controlled study.
  
  
  METHODS
  Outpatient clinics in two university hospitals and two teaching hospitals in The Netherlands.
  
  
  METHODS
  One hundred fifty-two healthy hysterectomized postmenopausal women.
  
  
  METHODS
  Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17beta-E2, 50 microg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 microg (n = 33), followed by four cycles of placebo in each group.
  
  
  METHODS
  Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17.
  
  
  RESULTS
  Mean (+/-SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 +/- 2.5 micromol/L vs. 8.2 +/- 2.0 micromol/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 micromol/L vs. 8.6 +/- 2.0 micromol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R G V
authors.initials: RG
authors.lastname: Smolders
authors.forename: M J
authors.initials: MJ
authors.lastname: van der Mooren
authors.forename: T
authors.initials: T
authors.lastname: Teerlink
authors.forename: J M W M
authors.initials: JM
authors.lastname: Merkus
authors.forename: M V A M
authors.initials: MV
authors.lastname: Kroeks
authors.forename: H R
authors.initials: HR
authors.lastname: Franke
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: P
authors.initials: P
authors.lastname: Kenemans
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods; D005215:Fasting; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007044:Hysterectomy; D009652:Norpregnenes / Q000627:therapeutic use*; D010352:Patient Dropouts; D018579:Patient Selection; D010919:Placebos; D017698:Postmenopause; D045167:Progesterone Congeners / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D009652:Norpregnenes; D010919:Placebos; D045167:Progesterone Congeners; D006710:Homocysteine; C033273:Gestodene; D004958:Estradiol; D005640:Follicle Stimulating Hormone