Placement of the vaginal 17beta-estradiol tablets in the inner or outer one third of the vagina affects the preferential delivery of 17beta-estradiol toward the uterus or periurethral areas, thereby modifying efficacy and endometrial safety.
OBJECTIVE
The purpose of this study was to investigate whether the effects of 17beta-estradiol tablets that are designed for the treatment of postmenopausal urovaginal atrophy are influenced by the site of placement into the vagina.


METHODS
In this controlled crossover trial, 10 postmenopausal women received a single 17beta-estradiol tablet in the outer or inner one third of the vagina. Before and 3 hours after treatment, the pulsatility index, resistance index, and blood flow were evaluated in the uterine and periurethral vessels by Doppler examination. Parallel 17beta-estradiol serum evaluations were performed.


RESULTS
Comparable and significant increases in 17beta-estradiol were observed. After inner administration, the pulsatility index and resistance index of both uterine arteries decreased; uterine artery blood flow increased significantly (P <.0001) but decreased in periurethral vessels (P <.02). After outer administration, the uterine artery pulsatility index, resistance index, and blood flow did not change, and the periurethral blood flow significantly increased (P <.0001).


CONCLUSIONS
For optimizing the efficacy while minimizing the risk of endometrial hyperplasia, 17beta-estradiol tablets must be placed in the outer one third of the vagina.
Cicinelli
Ettore
E
First Department of Obstetrics and Gynecology, University of Bari, Bari, Italy. cicinelli@gynecology1.uniba.it
Di Naro
Edoardo
E
De Ziegler
Dominique
D
Matteo
Maria
M
Morgese
Stella
S
Galantino
Pietro
P
Brioschi
Pierre-Alain
PA
Schonauer
AndSergio
A
D000282:Administration, Intravaginal; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011673:Pulsatile Flow; D014521:Urethra / Q000187:drug effects*; D014599:Uterus / Q000098:blood supply / Q000187:drug effects*; D014621:Vagina / Q000187:drug effects*; D014655:Vascular Resistance
D004958:Estradiol; D005640:Follicle Stimulating Hormone