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, endom etrium, and vascular reactivity of uterine arteries of sequential transderm al estradiol (50 mu g/day) and norethisterone (0.25 mg/day in the last 14 d ays of each cycle). Design: An intravaginal ultrasound evaluation was performed in 48 postmenop ausal women before and at the 3rd and 12th month of treatment, during the l ast 3 days of both estradiol alone and estradiol plus norethisterone. An en dometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeat ed after 48 months of treatment. Results: Uterine volume (33.7 +/- 3.3 cm(3) to 56.8 +/- 3.7 cm(3); p = 0.00 1) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.0 01) increased within 3 months, with no further increases. Thickness was sim ilar in the estradiol and estradiol-norethisterone phase. Endometrial hyper plasia was found in one participant at 12 months of treatment. A significan t decrease (p = 0.002) in the pulsatility index of uterine arteries was obs erved only during the estradiol phase. After 48 months of treatment, the pu lsatility 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 nor ethisterone reduces uterine artery resistance and induces a self-limiting g rowth of the uterus and endometrium. (Menopause 2000;7:117-122. (C) 2000, T he North American Menopause Society.).