title: Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women.
abstract: OBJECTIVE
  Approximately 50% of postmenopausal women suffer from vaginal atrophy, and a large proportion of them choose intravaginal estrogen preparations administered for local action to avoid systemic exposure to estrogens and its associated risk of breast and uterine cancer. The primary objective of this study was the evaluation of the systematic bioavailability of estradiol and estrone and the pharmacokinetics of two of the most frequently used intravaginal estrogen preparations, namely Vagifem and Premarin cream.
  
  
  METHODS
  While immunobased assays could not previously provide accurate measurement of serum estrogen concentrations in postmenopausal women, we have used validated mass spectrometry assays to measure the pharmacokinetics of serum estradiol and estrone during the 24 hours following the seventh daily application of 25 microg estradiol (Vagifem) and 1 g (0.625 mg) conjugated estrogens (Premarin) cream in 10 postmenopausal women in each group.
  
  
  RESULTS
  Serum estradiol was increased on average by 5.4-fold from 3 to 17 pg/mL during the 24-hour period after daily administration of 25 microg estradiol or 1 g (0.625 mg) conjugated estrogens cream. Serum estrone, conversely, increased 150% with Vagifem and 500% with Premarin cream.
  
  
  CONCLUSIONS
  The present data using validated, accurate, and sensitive mass spectrometry assays of estrogens show that the Vagifem pill and Premarin cream, after 1 week of daily treatment, cause an approximately fivefold increase in serum estradiol in postmenopausal women, thus indicating that the effects are unlikely to be limited to the vagina and that systemic actions are expected after application of these intravaginal estrogen preparations.
authors.affiliation: Oncology and Molecular Endocrinology Research Center, Laval University Hospital Research Center (CRCHUL) and Laval University, Quebec, Canada. Fernand.Labrie@crchul.ulaval.ca
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: Leonello
authors.initials: L
authors.lastname: Cusan
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Gomez
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côté
authors.forename: René
authors.initials: R
authors.lastname: Bérubé
authors.forename: Patrick
authors.initials: P
authors.lastname: Bélanger
authors.forename: Céline
authors.initials: C
authors.lastname: Martel
authors.forename: Claude
authors.initials: C
authors.lastname: Labrie
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004967:Estrogens / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004970:Estrone / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D004970:Estrone; D004958:Estradiol