Transdermal administration of estradiol and norethisterone: effect on the uterus and uterine arteries.
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.
Cagnacci
A
A
Institute of Obstetrics and Gynecology, University of Modena, Italy.
Arangino
S
S
Draetta
F P
FP
Angiolucci
M
M
Volpe
A
A
Melis
G B
GB
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
D004958:Estradiol; D009640:Norethindrone