title: A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.
abstract: OBJECTIVE
  To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women.
  
  
  METHODS
  Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens.
  
  
  RESULTS
  Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C.
  
  
  CONCLUSIONS
  Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.
authors.affiliation: Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, MA 02114, USA. jshifren@partners.org
authors.forename: Jan L
authors.initials: JL
authors.lastname: Shifren
authors.forename: Sophie
authors.initials: S
authors.lastname: Desindes
authors.forename: Marilyn
authors.initials: M
authors.lastname: McIlwain
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.forename: Norman A
authors.initials: NA
authors.lastname: Mazer
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000097:blood; D018592:Cross-Over Studies; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D011374:Progesterone / Q000008:administration & dosage*; D013739:Testosterone / Q000097:blood; D013974:Thyroxine / Q000097:blood; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D004966:Estrogens, Conjugated (USP); C027091:cortisol binding globulin; D013739:Testosterone; D011374:Progesterone; D013974:Thyroxine