title: Transdermal administration of estradiol and norethisterone: effect on the uterus and uterine arteries.
abstract: OBJECTIVE
  To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 microg/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle).
  
  
  METHODS
  An intravaginal ultrasound evaluation was performed in 48 postmenopausal women before and at the 3rd and 12th month of treatment, during the last 3 days of both estradiol alone and estradiol plus norethisterone. An endometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeated after 48 months of treatment.
  
  
  RESULTS
  Uterine volume (33.7 +/- 3.3 cm3 to 56.8 +/- 3.7 cm3; p = 0.001) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.001) increased within 3 months, with no further increases. Thickness was similar in the estradiol and estradiol-norethisterone phase. Endometrial hyperplasia was found in one participant at 12 months of treatment. A significant decrease (p = 0.002) in the pulsatility index of uterine arteries was observed only during the estradiol phase. After 48 months of treatment, the pulsatility index of uterine arteries was lower than at baseline (2.78 +/- 0.24 vs. 2.23 +/- 0.33; p = 0.044) even when evaluated in the combined phase.
  
  
  CONCLUSIONS
  The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium.
authors.affiliation: Institute of Obstetrics and Gynecology, University of Modena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cagnacci
authors.forename: S
authors.initials: S
authors.lastname: Arangino
authors.forename: F P
authors.initials: FP
authors.lastname: Draetta
authors.forename: M
authors.initials: M
authors.lastname: Angiolucci
authors.forename: A
authors.initials: A
authors.lastname: Volpe
authors.forename: G B
authors.initials: GB
authors.lastname: Melis
mesh_terms: D000279:Administration, Cutaneous; D001158:Arteries / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage*; D011673:Pulsatile Flow / Q000187:drug effects; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D004958:Estradiol; D009640:Norethindrone