Uterine and vaginal effects of unopposed ultralow-dose transdermal estradiol.
OBJECTIVE
To investigate uterine effects of unopposed ultralow-dose transdermal estradiol administered to postmenopausal women for 2 years.


METHODS
Postmenopausal women (n = 417), aged 60-80 years, with a uterus and with bone mineral density that was normal for age (z score >or=-2.0) were randomly assigned to receive unopposed transdermal estradiol (14 microg per day) or identical placebo patch. We evaluated effects on endometrial histology, vaginal bleeding, and vaginal epithelial cell maturation.


RESULTS
At baseline, estradiol and placebo groups were similar in age (67 +/- 5 years) and in median baseline serum estradiol level (4.8 pg/mL, interquartile range 2.7, 8.0 pg/mL). In the estradiol group, median estradiol level increased to 8.6 pg/mL, (interquartile range 4.4, 13.9 pg/mL, P < .001). In the estradiol group, focal atypical endometrial hyperplasia developed in 1 woman, and adenosarcoma of the uterus developed in 1 woman. The placebo group had no endometrial hyperplasia. Endometrial proliferation occurred in 8.5% of the estradiol group and in 1.1% of the placebo group (P = .06). Incidence of vaginal bleeding was 12.4% in the estradiol group and 8.6% in the placebo group (P = .3). Vaginal epithelial cells showed greater maturation in the estradiol group than in the placebo group (P < .001) but less than typically observed with standard doses of estrogen.


CONCLUSIONS
During 2 years of treatment with ultralow-dose unopposed estradiol, treatment and placebo groups had similar rates of endometrial hyperplasia, endometrial proliferation, and vaginal bleeding. This therapy apparently causes little or no endometrial stimulation.


METHODS
I.
Johnson
Susan R
SR
Department of Obstetrics and Gynecology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City 52242, USA. susan-johnson@uiowa.edu
Ettinger
Bruce
B
Macer
Judith L
JL
Ensrud
Kristine E
KE
Quan
Judy
J
Grady
Deborah
D
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D019584:Hot Flashes / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D014621:Vagina / Q000187:drug effects* / Q000473:pathology
D004958:Estradiol